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Cited by 497Epigenetics and DNA MethylationGenomics and Chromatin DynamicsChromatin Remodeling and Cancer

Epigenetics and cancer

Open access
Lund, Anders H., van Lohuizen, Maarten·2004·Genes & Development
DOI 10.1101/gad.1232504
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Abstract

Epigenetic mechanisms act to change the accessibility of chromatin to transcriptional regulation locally and globally via modifications of the DNA and by modification or rearrangement of nucleosomes. Epigenetic gene regulation collaborates with genetic alterations in cancer development. This is evident from every aspect of tumor biology including cell growth and differentiation, cell cycle control, DNA repair, angiogenesis, migration, and evasion of host immunosurveillance. In contrast to genetic cancer causes, the possibility of reversing epigenetic codes may provide new targets for therapeutic intervention.

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Crossref · 10.1101/gad.1232504

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  • Interpretationreasoning
    § REVIEW Epigenetics and cancer

    Epigenetic gene regulation works together with genetic changes in cancer development.

    “Epigenetic gene regulation collaborates with genetic alterations in cancer development.”
    Quote in the paperSubstantial claim
  • Interpretationreasoning
    § REVIEW Epigenetics and cancer

    Evidence for epigenetic collaboration with genetic alterations appears in all major aspects of tumor biology, including growth and differentiation, cell cycle control, DNA repair, angiogenesis, migration, and immune evasion.

    “This is evident from every aspect of tumor biology including cell growth and differentiation, cell cycle control, DNA repair, angiogenesis, migration, and evasion of host immunosurveillance.”
    Quote in the paperNot a substantial claim
  • Interpretationreasoning
    § REVIEW Epigenetics and cancer

    Some genes, such as cell cycle checkpoint genes and genes responding to external stimuli like growth factors or cell-cell contact, likely exist in a balanced state that is sensitive to dynamic histone modification changes, enabling rapid responses.

    “However, other genes, such as cell cycle checkpoint genes and genes directly affected by exogenous stimuli such as growth factors or cell-cell contact, likely reside in a balanced state sensitive to dynamic adjustments in histone modifications, thereby allowing for rapid responses to specific stimuli.”
    Quote in the paperNot a substantial claim
  • Premisecitation

    Phosphorylation of H3 Ser10 also facilitates acetylation of Lys9, preventing repressive Lys9 methylation marks.

    “Ser 10 phosphorylation also facilitates acetylation of Lys 9, thereby preventing the setting of repressive Lys 9 methylation marks (Rea et al. 2000).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Rea et al. 2000

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  • Premisereasoning
    § REVIEW Epigenetics and cancer

    Epigenetic gene regulation generally has high integrity and stability.

    “Not surprisingly therefore, epigenetic gene regulation is characterized overall by a high degree of integrity and stability.”
    Quote in the paperNot a substantial claim
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  • Classified as probably not a substantial claim. 19

  • May combine two claims.

    Interpretationreasoning
    § REVIEW Epigenetics and cancer

    Because epigenetic codes can potentially be reversed, unlike genetic causes, they offer new therapeutic targets.

    “In contrast to genetic cancer causes, the possibility of reversing epigenetic codes may provide new targets for therapeutic intervention.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Epigenetic changes that contribute to cancer can be reversed pharmacologically to produce therapeutic benefit.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    Variant histone proteins exist and can be inserted into nucleosomes, possibly serving as landmarks for specific cellular functions.

    “Aside from the core histones, a variety of variant histone proteins exist and can be inserted into the nucleosome, possibly serving as landmarks for specific cellular functions (discussed following).”
    Quote in the paperNot a substantial claim

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    Premisecitation

    Although PRC2 members are directly controlled by the RB tumor-suppressor pathway, their expression levels do not appear to fluctuate in a cell cycle-dependent manner.

    “Surprisingly, although PRC2 complex members are directly controlled by the RB tumor-suppressor pathway, their expression levels do not appear to fluctuate in a cell cycle-dependent manner (Weinmann et al. 2001;Bracken et al. 2003).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Weinmann et al. 2001

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    • cites Bracken et al. 2003

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    Premisecitation

    Histone modifications influence one another; for example, phosphorylation of histone H3 Ser10 facilitates acetylation of Lys14 and methylation of Lys4, producing open chromatin.

    “This is exemplified in gene activation where phosphorylation of histone H3 Ser 10 facilitates acetylation of Lys 14 and methylation of Lys 4, resulting in an open chromatin conformation (Cheung et al. 2000;Lo et al. 2000).”
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    • cites Cheung et al. 2000

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    • cites Lo et al. 2000

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The pattern of histone modifications indicates local chromatin status and is called the histone code.

    “The pattern of histone modifications signifies the status of the chromatin locally and has been coined the histone code (Strahl and Allis 2000).”
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    • cites Strahl and Allis 2000

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    Premisecitation
    § REVIEW Epigenetics and cancer

    Epigenetic programming is essential in mammalian development, and stable inheritance of epigenetic settings is needed for tissue- and cell-type-specific functions.

    “Epigenetic programming is crucial in mammalian development, and stable inheritance of epigenetic settings is essential for the maintenance of tissue-and cell-typespecific functions (Li 2002).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Li 2002

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    Interpretationreasoning

    These PRC2 functions indicate long-range transcriptional repression and suggest PRC2 activity may have global cellular consequences, perhaps by skewing the balance between specific histone methylation imprints.

    “These functions point to long-range mechanisms of transcriptional repression and suggest that PRC2 activity may have global consequences to the cell, perhaps via more generally skewing the balance between specific histone methylation imprints.”
    Quote in the paperNot a substantial claim

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    Premisereasoning

    Histone methylations can serve as anchorage points for both activator and repressor complexes and thereby contribute to epigenetic inheritance carrying information about differentiation commitment and function.

    “histone methylations can serve as anchorage points for both activator and repressor complexes and are thereby involved in conferring an epigenetic inheritance to the cell, carrying information related to differentiation commitment and function.”
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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The nucleosome consists of about two turns of DNA wrapped around a histone octamer containing two copies each of H2A, H2B, H3, and H4; linker histone H1 attaches between core nucleosomes and promotes compaction.

    “The nucleosome is made up of approximately two turns of DNA wrapped around a histone octamer built from two subunits of each histone, H2A, H2B, H3, and H4, respectively, In between core nucleosomes, the linker histone H1 attaches and facilitates further compaction (for a recent review, see Khorasanizadeh 2004).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Khorasanizadeh 2004

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    Premisenone given

    PcG proteins form transcriptional repressor modules divided into at least two complexes: PRC2, whose human core is EZH2, EED, and SUZ12, and PRC1, whose core proteins are RNF2, HPC, EDR, and BMI1.

    “Polycomb-group (PcG) proteins form transcriptional repressor modules that functionally can be divided into at least two distinct complexes: the initiation complex, Polycomb repression complex 2 (PRC2), the core of which in humans consists of EZH2, EED, and SUZ12; and the maintenance complex, PRC1, with the core proteins RNF2, HPC, EDR, and BMI1.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    Histone acetylation generally correlates with transcriptional activity.

    “Al-though histone acetylation in general correlates with transcriptional activity,”
    Quote in the paperNot a substantial claim

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    Interpretationcitation

    Experimental overexpression of EZH2 results in target gene suppression only, which does not support dominant-negative effects on PRC2.

    “however, experimental overexpression of EZH2 results in target gene suppression only (Varambally et al. 2002), and hence does not sustain a notion of dominant negative effects.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Varambally et al. 2002

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    Interpretationcitation

    The overexpression of EZH2 in cancers is likely causally related to tumorigenesis rather than a mere consequence of deregulated RB-E2F function, because the EZH2 locus is amplified in several cancers.

    “and the observed overexpression of EZH2 in cancers is likely causally related to tumorigenesis and not a mere consequence of deregulated RB-E2F functioning, as the EZH2 locus is amplified in several cancers (Bracken et al. 2003).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Bracken et al. 2003

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    Premisereasoning

    Most histone modifications are reversible, but no histone demethylase had been identified at the time, suggesting histone methylation participates in long-term regulation.

    “Although most histone modifications are reversible, no histone demethylase has been identified as yet, suggesting histone methylation to be involved in processes of long-term regulation.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    The N-terminal tails of histones protrude from nucleosomal core particles and act as regulatory registers for epigenetic signals.

    “The N-terminal tails of the histone proteins are protruding out from the nucleosomal core particles, and these tails serve as regulatory registers onto which epigenetic signals can be written.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    The SET domain in EZH2 methylates histone H3 at Lys9 and more prominently Lys27, and histone H1 at Lys26.

    “Recent data have demonstrated that the SET domain present in EZH2 is responsible for methylation of Lys 9 and, more prominently, Lys 27 of histone H3 (Cao et al. 2002;Czermin et al. 2002;Kuzmichev et al. 2002;Muller et al. 2002) and Lys 26 on histone H1 (Kuzmichev et al. 2004).”
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    • cites Cao et al. 2002

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    • cites Czermin et al. 2002

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    • cites Kuzmichev et al. 2004

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  • May combine two claims.

    Interpretationreasoning

    DNA methylation and histone modifications affect each other, forming a highly intricate epigenetic control mechanism.

    “Also DNA methylation affects histone modifications and vice versa, to make up a highly intricate epigenetic control mechanism, the impact of which we have only just begun to comprehend.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Members of both PcG and TrxG complexes contain SET domains.

    “Members of both PcG and TrxG protein complexes harbor SET domains.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    PRC2 is required for X-chromosome inactivation and for correct imprinting of autosomal loci.

    “The PRC2 complex is also required for X-chromosome inactivation (Plath et al. 2003;Silva et al. 2003) and for correct imprinting of autosomal loci (Wang et al. 2001b).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Plath et al. 2003

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    • cites Silva et al. 2003

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    • cites Wang et al. 2001b

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    Covalent histone modifications include acetylation of lysines, methylation of lysines and arginines, phosphorylation of serines and threonines, ADP-ribosylation of glutamic acids, and ubiquitination and sumoylation of lysines.

    “Covalent modification of histones includes acetylation of lysines, methylation of lysines and arginines, phosphorylations of serines and threonines, ADP-ribosylation of glutamic acids, and ubiquitination and sumolyation of lysine residues (Fig. 1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    Histone proteins can be mono-, di-, or trimethylated at lysine residues and mono- or dimethylated at arginine residues.

    “Histone proteins can be mono-, di-, or trimethylated at the ␧ amino group of lysine residues and either mono-or dimethylated at arginine residues.”
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    Interpretationnone given

    The causal role of EZH2 overexpression in tumorigenesis remains to be confirmed in mouse models.

    “This, however, remains to be confirmed in mouse models.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    SMYD3 interacts with the RNA polymerase II complex and activates target genes by methylating histone H3 Lys4.

    “SMYD3 was found to interact with the RNA polymerase II complex and activate target genes via methylation of histone H3 Lys 4.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    Evi1 was characterized in mouse as a cancer-related retroviral integration site in myeloid leukemia, and EVI1 was later identified as a translocation breakpoint in humans.

    “Evi1 was characterized in the mouse as a cancer-related retroviral integration site in myeloid leukemia (Morishita et al. 1988), and EVI1 was subsequently identified as a translocation breakpoint in hu-mans (Morishita et al. 1992).”
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    • cites Morishita et al. 1988

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    • cites Morishita et al. 1992

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    Interpretationcitation

    Mll heterozygous mice do not appear tumor prone, making haploinsufficiency a less likely cause of leukemogenesis.

    “Mll heterozygous mice do not appear tumor prone, making haploinsufficiency a less likely cause of leukemogenesis (Corral et al. 1996).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Corral et al. 1996

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    Premisecitation

    Suv39h deficiency in mouse predominantly affects heterochromatin stability, while Suv39h methyltransferases associate with numerous cell cycle regulatory proteins including pRB, PcG proteins, and SMADs.

    “Whereas Suv39h deficiency in the mouse predominantly was found to affect heterochromatin stability, the Suv39h methyltransferases associate with numerous proteins involved in cell cycle regulation including pRB (Nielsen et al. 2001;Vandel et al. 2001), PcG-proteins (Sewalt et al. 2002), and SMADs (Frontelo et al. 2004).”
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    • cites Nielsen et al. 2001

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    • cites Vandel et al. 2001

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    • cites Sewalt et al. 2002

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    Premisecitation

    SUV39H1 is the mammalian homolog of Drosophila Su(var)3-9 and was the first SET domain protein recognized as a histone methyltransferase.

    “SUV39H1 is the mammalian homolog of the Drosophila position effect variegation modifier Su(var)3-9 and was the first SET domain protein to be recognized as a histone methyl transferase (Rea et al. 2000).”
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    • cites Rea et al. 2000

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    Premisecitation

    The Ash1-specific methylation imprint displaces HP1 and PcG proteins from repressed genes and facilitates binding of the Brahma chromatin remodeling complex.

    “The Ash1-specific methylation imprint was found to displace HP1 and PcG proteins, which are normally bound to repressed genes, and instead facilitates the binding of the Brahma chromatin remodeling complex (Beisel et al. 2002).”
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    • cites Beisel et al. 2002

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    Interpretationreasoning

    This suggests functional redundancy between different epigenetic repression mechanisms, possibly explaining why loss of Suv39h-mediated repression does not produce a stronger phenotype.

    “This suggests a functional redundancy between different epigenetic gene repression mechanisms, which may serve to explain why loss of Suv39h-mediated repression does not have an even stronger phenotype.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given

    All MLL1 fusion proteins retain the N-terminal part of MLL1 and lose the C-terminal part encoding the SET domain.

    “Intriguingly, all fusion proteins retain the N-terminal part of MLL1, whereas the C-terminal part encoding the SET domain is lost.”
    Quote in the paperNot a substantial claim

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    Interpretationcitation

    Ectopic expression of RIZ1 in cancer cell lines causes cell cycle arrest and/or apoptosis, consistent with tumor-suppressive function.

    “In accordance with a tumor-suppressive function of RIZ1, ectopic expression in cancer cell lines results in cell cycle arrest and/or apoptosis (He et al. 1998;Jiang et al. 1999).”
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    • cites Jiang et al. 1999

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    Premisecitation

    RIZ1 was first isolated through its interaction with RB and was the first SET domain protein shown to be a tumor suppressor.

    “RIZ1, originally isolated from its interaction with the RB tumor suppressor protein (Buyse et al. 1995), was the first SET domain protein demonstrated to be a tumor suppressor (Steele-Perkins et al. 2001).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Buyse et al. 1995

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    • cites Steele-Perkins et al. 2001

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    Premisecitation

    Mice deficient for the two Suv39 homologs show chromosomal instability and are prone to B-cell lymphomas resembling human non-Hodgkin lymphomas, with long latency.

    “Mice deficient for the two Suv39 homologs display chromosomal instability and are prone to develop B-cell lymphomas resembling human non-Hodgkin lymphomas, albeit with long latency (Peters et al. 2001).”
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    • cites Peters et al. 2001

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    Premisecitation

    In ES cells lacking both Suv39 homologs, pericentromeric heterochromatin lacks the characteristic H3 Lys9 trimethylation and instead accumulates monomethylated Lys9 and trimethylated Lys27.

    “In embryonic stem (ES) cells lacking both Suv39 homologs the pericentromeric heterochromatin is devoid of the characteristic trimethylation of histone H3, Lys 9. Instead, an alternative methylation imprint consisting of monomethylated Lys 9 and trimethylated Lys 27 has accumulated (Peters et al. 2003).”
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    • cites Peters et al. 2003

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    Premisenone given

    The 5' MDS part of MDS-EVI1 contains a SET domain, and both mouse retroviral integrations and human translocations cause selective overexpression of the EVI1 variant lacking the SET domain.

    “The 5Ј MDS part of MDS-EVI1 contains a SET domain, and both retroviral integrations in the mouse and translocations in humans result in the selective overexpression of the EVI1 variant lacking a SET domain.”
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    Premisecitation

    SMYD3 is a SET and MYND domain-containing protein overexpressed in colorectal and hepatocellular carcinomas.

    “SMYD3 was recently identified as a SET and MYND domain-containing protein overexpressed in colorectal carcinomas and hepatocellular carcinomas (Hamamoto et al. 2004).”
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    • cites Hamamoto et al. 2004

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    Premisecitation

    Only RIZ1 contains a SET domain and appears to be the main target of inactivation in tumors.

    “Interestingly, only RIZ1 harbors a SET domain and appears to be the main target of inactivation in tumors (Huang 2002),”
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    • cites Huang 2002

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    Premisecitation

    Overexpression of SMYD3 results in colony formation of NIH 3T3 cells, but its oncogenic capacity has not been confirmed in vivo.

    “Whereas the oncogenic capacity of SMYD3 is yet to be confirmed in an in vivo model, overexpression of SMYD3 results in colony formation of NIH 3T3 cells.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    Reduced histone H3 methylation from loss of Suv39h decreases HP1 association with telomeres and causes abnormal telomere elongation.

    “The reduced histone H3 methylation resulting from loss of Suv39h caused a decrease in HP1 association to the telomeres and abnormal telomere elongation (Garcia- Cao et al. 2004).”
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    • cites Garcia-Cao et al. 2004

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    Premisecitation

    More than 40 specific translocations involving MLL1 have been described in human cancers.

    “More than 40 specific translocations involving MLL1 have been described in human cancers to date (Ayton and Cleary 2001).”
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    • cites Ayton and Cleary 2001

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    Premisenone given

    The MYND domain appears to confer sequence-specific binding to target genes.

    “Interestingly, the MYND domain appears to confer sequence-specific binding to target genes.”
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    Interpretationcitation

    RNAi-mediated knockdown of HDAC2 in colonic cancer cells causes cell death, indicating HDAC2 protects cancer cells against apoptosis.

    “Likewise, RNAi-mediated knockdown of HDAC2 in colonic cancer cells resulted in cell death, indicating a role for HDAC2 in protecting cancer cells against apoptosis (Zhu et al. 2004a).”
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    • cites Zhu et al. 2004a

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    Premisenone given

    Many transcriptional regulators, chromatin modifiers, and intracellular signal transducers are posttranslationally modified by acetylation.

    “Aside from histones, many transcriptional regulators, chromatin modifiers, and intracellular signal transducers are posttranslationally modified by acetylation.”
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    Premisecitation

    Dnmt1 is necessary and sufficient for Fos-induced transformation of mouse fibroblast cells.

    “Dnmt1 was shown to be necessary and sufficient for Fos-induced transformation of mouse fibroblast cells (Bakin and Curran 1999),”
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    • cites Bakin and Curran 1999

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    Premisecitation

    Important tumor-suppressor mechanisms depend on HDAC function, as RB requires HDAC1 for transcriptional repression of E2F target genes.

    “On the other hand is the reliance of important tumorsuppressor mechanisms on HDAC function, as exemplified by the dependency of RB on HDAC1 for transcriptional repression of E2F target genes (Luo et al. 1998;Magnaghi-Jaulin et al. 1998;Robertson et al. 2000).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Luo et al. 1998

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    • cites Magnaghi-Jaulin et al. 1998

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    • cites Robertson et al. 2000

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  • May combine two claims.

    Interpretationcitation

    DNA methylation is tightly connected to cancer development and can act as a double-edged sword.

    “DNA methylation is tightly connected to cancer development and can act as a double-edged sword.”
    Quote in the paperSubstantial claim

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    Premisenone given

    DNMT1 associates with the DNA replication fork and acts as a hemi-methylase maintaining correct methylation patterns during DNA replication.

    “DNMT1 associates with the DNA replication fork and functions as a hemi-methylase responsible for maintaining correct methylation patterns on DNA replication.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    All three methyltransferase enzymes are overexpressed in human tumors, although only to moderate levels.

    “All three methyltransferase enzymes have been found to be overexpressed in human tumors, although to moderate levels only (De Marzo et al. 1999;Robertson et al. 1999;Girault et al. 2003;Nagai et al. 2003).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites De Marzo et al. 1999

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    • cites Robertson et al. 1999

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    • cites Girault et al. 2003

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    Premisecitation

    CpG islands are most often associated with promoter regions, and an estimated 60% of human genes contain a CpG island.

    “CpG islands are most often associated with promoter regions and an estimated 60% of human genes contain a CpG island (Antequera and Bird 1993).”
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    • cites Antequera and Bird 1993

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    Premisecitation

    Germ-line mutations in DNMT3B underlie ICF syndrome, a rare disorder characterized by immunodeficiency, centromeric instability, and facial abnormalities.

    “Germ-line mutations in DNMT3B underlies ICF syndrome, a rare disorder characterized by immunodeficiency, centromeric instability, and facial abnormalities (Hansen et al. 1999;Xu et al. 1999).”
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    • cites Hansen et al. 1999

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    • cites Xu et al. 1999

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    Premisecitation

    Hdac1-deficient mice are not viable, and ES cells with homozygous Hdac1 deletion show proliferation defects correlated with increased p21 and p27, demonstrating HDAC1 involvement in cell cycle regulation.

    “Hdac1-deficient mice are not viable and ES cells with homozygous Hdac1 deletion display proliferation defects correlating with increased levels of the cyclin-dependent kinase inhibitors p21 and p27 (Lagger et al. 2002), demonstrating the involvement of HDAC1 in cell cycle regulation.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Lagger et al. 2002

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    Premisecitation

    Germ-line mutations in CBP cause Rubenstein-Taybi syndrome, and these patients have increased cancer risk.

    “Germ-line mutations in CBP causes the developmental disorder Rubenstein-Taybi syndrome, and these patients suffer an increased cancer risk (Petrij et al. 1995;Murata et al. 2001).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Petrij et al. 1995

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    • cites Murata et al. 2001

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    Premisenone given

    No arginine-specific methyltransferases have been implicated in cancer development yet, but several are involved in gene regulatory complexes important for cell cycle regulation.

    “Although no arginine-specific methyltransferases have been implicated in cancer development yet, several of these enzymes are involved in gene regulatory complexes important for cell cycle regulation.”
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    Premisecitation

    PRMT5 associates with and negatively regulates the cyclin E promoter.

    “PRMT5 was furthermore found to associate with and negatively regulate the cyclin E promoter (Fabbrizio et al. 2002).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Fabbrizio et al. 2002

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    Premisecitation

    DNA methylation patterns are established during early embryogenesis through the interplay of at least three active DNA methyltransferases, DNMT1, DNMT3A, and DNMT3B, and targeted deletions in mouse show these enzymes are essential for normal development.

    “Patterns of DNA methylation are laid out during early embryogenesis via the interplay of at least three active DNA methyltransferases, DNMT1, DNMT3A, and DNMT3B, and targeted deletions of these genes in the mouse have demonstrated that the enzymes are essential for normal development (Li et al. 1992;Okano et al. 1999).”
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    • cites Li et al. 1992

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    • cites Okano et al. 1999

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    Premisecitation

    Methylation at the C-5 position of cytosine in CpG dinucleotides by DNMTs evolved relatively late and is generally considered to facilitate static long-term gene silencing and confer genome stability by repressing transposons and repetitive DNA.

    “Methylation at the C-5 position of cytosine residues present in CpG dinucleotides by DNMTs has evolved relatively late in evolution and is generally considered to facilitate static long-term gene silencing and to confer genome stability through repression of transposons and repetitive DNA elements (Yoder et al. 1997).”
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    • cites Yoder et al. 1997

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    Premisecitation

    Hdac2 is genetically linked to the Wnt pathway, as Hdac2 is overexpressed in tumors and tissues from mice lacking the APC tumor suppressor.

    “Recently, Hdac2 was genetically linked to the Wnt pathway, as Hdac2 is overexpressed in tumors and tissues from mice lacking the adenomatosis polyposis coli (APC) tumor suppressor (Zhu et al. 2004a).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Zhu et al. 2004a

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  • May combine two claims.

    Premisecitation

    PRMT5 can methylate histone H3 and H4 in vitro and interacts directly with SWI/SNF components.

    “The PRMT5 arginine methyltransferase can methylate both histone H3 and H4 in vitro and interacts directly with components of the SWI/SNF complex (Pal et al. 2003).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Pal et al. 2003

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  • May combine two claims.

    Interpretationcitation

    Mouse embryo fibroblasts deficient for Dnmt3b are resistant to transformation by SV40 large T and activated Ras oncogenes, demonstrating that epigenetic and genetic mechanisms likely act together during cellular transformation.

    “Interestingly, mouse embryo fibroblasts deficient for Dnmt3b are resistant to transformation by SV40 largeT and activated Ras oncogenes (Soejima et al. 2003), demonstrating that epigenetic and genetic mechanisms likely act in concert during cellular transformation.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Soejima et al. 2003

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  • May combine two claims.

    Premisecitation

    Oncogenesis is promoted by local hypermethylation of tumor-suppressor genes, while global genomic hypomethylation affects oncogene expression and genomic stability.

    “On the one hand, oncogenesis is promoted by local hypermethylation of tumor-suppressor genes, whereas global genomic hypomethylation, on the other hand, affects oncogene expression and genomic stability (Jones and Baylin 2002).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Jones and Baylin 2002

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  • May combine two claims.

    Premisecitation

    Acetylation of histone proteins correlates with transcriptional activation, and a dynamic equilibrium of histone acetylation is governed by opposing HATs and HDACs.

    “Acetylation of histone proteins correlates with transcriptional activation and a dynamic equilibrium of histone acetylation is governed by the opposing actions of HATs and histone deacetylases (HDACs) (for recent reviews, see Marks et al. 2001;Yang 2004).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Marks et al. 2001

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    • cites Yang 2004

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  • May combine two claims.

    Premisecitation

    CpG dinucleotides are statistically underrepresented in the genome, likely because cytosine methylation makes them more susceptible to deamination, but are locally enriched in CpG islands.

    “CpG dinucleotides are statistically underrepresented in the genome, likely because methylation of cytosine makes them more susceptible to deamination, but are locally enriched in shorter stretches of DNA (0.5 to several kilobases) known as CpG islands (Bird 2002).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Bird 2002

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Both CBP and p300 genes reside in regions frequently lost in tumors, and cancer-specific mutations abolishing p300 enzymatic activity have been identified.

    “Both genes reside in regions frequently lost in tumors, and cancerspecific mutations abolishing the enzymatic activity of p300 have been identified (Muraoka et al. 1996;Gayther et al. 2000;Ozdag et al. 2002).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Muraoka et al. 1996

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    • cites Gayther et al. 2000

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    • cites Ozdag et al. 2002

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  • May combine two claims.

    Premisecitation

    Regulatory regions of many genes, including tumor suppressors, contain repetitive sequence islands, some of which influence transcription.

    “the regulatory regions of many genes (including known tumor suppressors) contain islands of repetitive sequences, some of which have been shown to influence transcriptional regulation (Jordan et al. 2003;Kelly 2003).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Jordan et al. 2003

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    • cites Kelly 2003

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Loss of IGF2 imprinting was suggested as a predictive marker for colorectal cancer.

    “Loss of imprinting of the IGF2 gene was recently suggested as a predictive marker for colorectal cancer (Cui et al. 2003).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Cui et al. 2003

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  • May combine two claims.

    Premisecitation

    CTCF is involved in imprinting and is required to protect against de novo methylation.

    “CTCF is involved in the regulation of imprinting, where it is required to protect against de novo methylation (Fedoriw et al. 2004;Lewis and Murrell 2004).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Fedoriw et al. 2004

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    • cites Lewis and Murrell 2004

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  • May combine two claims.

    Interpretationcitation

    Hypermethylation of tumor-suppressor genes may be an early event in cancer development, suggesting epigenetic and mutational causes may collaborate from an early time point.

    “Also, hypermethylation of tumor-suppressor genes may be an early event in cancer development (Waki et al. 2003;Lee et al. 2004;Suter et al. 2004), suggesting that epigenetic and mutational cancer causes may collaborate from an early time point in disease progression.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Waki et al. 2003

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    • cites Lee et al. 2004

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    • cites Suter et al. 2004

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    DNMTs may preferentially bind damaged or mismatched DNA.

    “it has been suggested that DNMTs may preferentially bind to damaged or mismatched DNA (James et al. 2003).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites James et al. 2003

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Epigenetic induction of a classical mutator phenotype through transcriptional inactivation of MLH1 has been proposed to account for microsatellite instability in colorectal cancers.

    “Epigenetic induction of a classical mutator phenotype via transcriptional inactivation of the DNA mismatch repair gene MLH1 has been proposed to account for microsatellite instability in colorectal cancers (Kane et al. 1997;Herman et al. 1998;Toyota et al. 1999a,b),”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Kane et al. 1997

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    • cites Herman et al. 1998

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    • cites Toyota et al. 1999a,b

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  • May combine two claims.

    Premisecitation

    In contrast to hypermethylation of tumor-suppressor genes, tumor cells globally display overall hypomethylation of DNA, and hypomethylation was the first epigenetic mechanism linked to cancer development.

    “In contrast to hypermethylation of tumor-suppressor genes, tumor cells globally display an overall hypomethylation of DNA (Feinberg and Vogelstein 1983a;Goelz et al. 1985) and hypomethylation was the first epigenetic mechanism to be linked to cancer development (Feinberg and Tycko 2004).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Feinberg and Vogelstein 1983a

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    • cites Goelz et al. 1985

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    • cites Feinberg and Tycko 2004

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  • May combine two claims.

    Interpretationcitation

    Global genomic demethylation appears to progress with age in a tissue-dependent manner and may partly explain the higher cancer incidence among the elderly.

    “Global genomic demethylation appears to progress with age in a tissue-dependent manner (Richardson 2003) and may in part explain the higher incidence of cancer among the elderly.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Richardson 2003

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  • May combine two claims.

    Premisecitation

    Genomic hypomethylation can cause genomic instability, likely because demethylation predisposes to DNA strand breakage and recombination within derepressed repetitive sequences.

    “Genomic hypomethylation may furthermore cause genomic instability, presumably because demethylation predisposes to DNA strand breakage and recombination within derepressed repetitive sequences (for review, see Ehrlich 2002).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Ehrlich 2002

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    Premisecitation

    BRG1/BRM expression is lost in 10% of primary lung tumors and correlates with poor prognostic outcome.

    “BRG1/BRM expression was found lost in 10% of primary lung tumors correlating with a poor prognostic outcome (Reisman et al. 2003).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Reisman et al. 2003

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  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    Noncoding antisense RNA drives DNA methylation.

    “Noncoding antisense RNA driving DNA methylation”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    H2AX marks DNA double-strand breaks, and H2AX-deficient cells have increased genomic instability and impaired formation of radiation-induced foci of DNA repair proteins such as BRCA1.

    “The H2A variant H2AX marks DNA double-strand breaks, and H2AX-deficient cells have increased genomic instability and impaired forma-tion of radiation-induced foci of DNA repair proteins such as BRCA1 (Bassing et al. 2002;Celeste et al. 2002).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Bassing et al. 2002

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    • cites Celeste et al. 2002

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  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    DNA methylation drives histone modification.

    “DNA methylation driving histone modification”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In mammals and flies, HP1 acts dose-dependently: heterozygotes show partial loss of gene silencing and overexpression increases silencing.

    “In both mammals and flies, HP1 acts in a dosage-dependent manner with heterozygotes displaying a partial loss of gene silencing and HP1 overexpression resulting in an increase in silencing (Eissenberg et al. 1992;Festenstein et al. 1999).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Eissenberg et al. 1992

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    • cites Festenstein et al. 1999

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  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    Histone modification directs DNA methylation.

    “Histone modification directing DNA methylation”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In mammals, HP1α and HP1β localize to pericentric heterochromatin and minor euchromatic sites, while HP1γ localizes predominantly to euchromatin.

    “HP1␣ and HP1␤ localize to pericentric heterochromatin and minor sites within euchromatin, whereas HP1␥ localizes predominantly to euchromatic regions (Eissenberg and Elgin 2000).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Eissenberg and Elgin 2000

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  • May combine two claims.

    Interpretationcitation

    These studies place Bmi1 and epigenetic gene regulation central to the tumor stem cell concept, in which cells escape growth control and activate a stem cell-like self-renewal program.

    “These studies place Bmi1, and thereby epigenetic gene regulation, central to the emerging concept of tumor stem cells, which aside from having escaped cellular growth control mechanisms such as the p53 and the pRB pathways, also have (re)instigated a stem cell-like transcription program that allows for continuous self-renewal (Pardal et al. 2003;Valk-Lingbeek et al. 2004).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Pardal et al. 2003

      Not checked in the free run.

    • cites Valk-Lingbeek et al. 2004

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    CENP-A is overexpressed and mislocalized in primary human colorectal tumors, suggesting a link between CENP-A deregulation and aneuploidy.

    “CENP-A was recently found to be overexpressed and mislocalized in primary human colorectal tumors, suggesting a link between CENP-A deregulation and aneuploidy (Tomonaga et al. 2003).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Tomonaga et al. 2003

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    HP1α expression is down-regulated in invasive human breast cancer cells, and overexpression of HP1α diminishes invasive potential.

    “the expression of HP1␣ is reportedly down-regulated in invasive human breast cancer cells, and overexpression of HP1␣ results in diminished invasive potential (Kirschmann et al. 2000).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Kirschmann et al. 2000

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  • May combine two claims.

    Premisecitation

    Loss of Suv39h in mice displaces HP1 proteins from pericentromeric heterochromatin, resulting in aneuploidy and cancer.

    “Loss of Suv39h in mice results in the displacement of HP1 proteins from pericentromeric heterochromatin, resulting in anaploidy and cancer (Peters et al. 2001).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Peters et al. 2001

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83 of 83

  • The paper relies on this without support.

    Epigenetic changes that contribute to cancer can be reversed pharmacologically to produce therapeutic benefit.

    “In contrast to genetic cancer causes, the possibility of reversing epigenetic codes may provide new targets for therapeutic intervention.”

  • The paper relies on this without support.

    Understanding the molecular details of epigenetic cancer mechanisms will translate into new drug development strategies.

    “Understanding the molecular details behind”

  • The paper relies on this without support.

    Findings from model organisms and cell lines are informative about human cancer epigenetics.

    “Mouse models have further validated a role for genomic hypomethylation in tumor formation”

  • The paper relies on this without support.

    Epigenetic alterations observed in cancer cell lines and xenografts reflect primary human tumor biology.

    “MBD2 knockdown in human cancer cell lines was found to suppress tumorigenesis in a mouse xenograft model”

  • The authors state this as an assumption.

    Reversal of epigenetic silencing will reinstate cellular cancer defense mechanisms.

    “The fundamental principle behind this type of epigenetic therapy is that reversal of epigenetic silencing will reinstate cellular cancer defense mechanisms”

  • The paper relies on this without support.

    There is limited knowledge about possible adverse effects in patients.

    “relatively little is known about potential side effects in patients”

  • The paper relies on this without support.

    Not all epigenetic marks are known.

    “not all epigenetic marks are known”

  • The paper relies on this without support.

    Only few of the known epigenetic marks are understood in any detail.

    “only few of the known ones are understood in any detail”
8 of 8

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Cites

2 retracted

Flagged first, then by citations

3 of the 290 references couldn’t be matched to a known paper.

Research works printed but not linked: 26

  1. 2001, Cancer Res., 61, 2409
  2. 1999, Cancer Res., 59, 74
  3. 1999, Cancer Res., 59, 3855
  4. 2002, Cancer Res., 62, 4736
  5. 2001, Cancer Res., 61, 8094
  6. 2000, Cancer Res., 60, 2368
  7. 2001, Cancer Res., 61, 3225
  8. 2003, Clin. Cancer Res., 9, 4415
  9. 1995, Cancer Res., 55, 5195
  10. 1998, Cancer Res., 58, 4238
  11. 1995, Cancer Res., 55, 4525
  12. 1997, Cancer Res., 57, 808
  13. 2003, Cancer Res., 63, 7619
  14. 2000, Cancer Res., 60, 3359
  15. 1996, Oncogene, 12, 1565
  16. 1998, Cancer Res., 58, 591
  17. 2002, Curr. Issues Mol. Biol., 4, 111
  18. 1993, Oncogene, 8, 1063
  19. 2003, Int. J. Oncol., 23, 1663
  20. 2003, Cancer Res., 63, 1114
  21. 2003, Cancer Res., 63, 560
  22. 2003, Cancer Res., 63, 3511
  23. 1999, Cancer Res., 59, 5438
  24. 2002, Cancer Res., 62, 2378
  25. 1999, Nat. Genet., 23, 62
  26. 2000, Cancer Res., 60, 6171

Cited by

Sorted by citations

Related

Authors
Lund, A. H., & van Lohuizen, M.
Affiliations
The Netherlands Cancer Institute (NL)
ORCID
Lund, Anders H.
Venue
Genes & Development
Publisher
Cold Spring Harbor Laboratory
Published
2004-10-01
Volume
18
Issue
19
Pages
2315-2335
ISSN
  • 0890-9369 (ISSN-L)
  • 1549-5477
DOI
10.1101/gad.1232504
OpenAlex
W2136492640
Semantic Scholar
a8eac694f349babbcdf21346ba0dfed461fa4e4f
Cited by
489
References
290
Citations by year
2026: 5 · 2025: 3 · 2024: 5 · 2023: 9 · 2022: 9 · 2021: 15 · 2020: 11 · 2019: 13 · 2018: 11 · 2017: 19 · 2016: 23 · 2015: 22 · 2014: 25 · 2013: 34 · 2012: 23
Type
posted content
Language
en
Open access
Locations
  • Genes & Development (publishedVersion)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords
epigenetics, cancer, chromatin accessibility, DNA methylation, histone modifications, transcriptional regulation, tumor biology, cell cycle regulation, DNA repair, angiogenesis, cell migration, immune evasion, epigenetic therapy
MeSH terms
Cell Cycle, Cell Differentiation, Cell Division, DNA Repair, Gene Expression Regulation, Humans, Neoplasms, Neovascularization, Pathologic

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-06.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.

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