The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.
Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3′ exons of TACSTD1
Abstract
Lynch syndrome patients are susceptible to colorectal and endometrial cancers owing to inactivating germline mutations in mismatch repair genes, including MSH2 (ref. 1). Here we describe patients from Dutch and Chinese families with MSH2-deficient tumors carrying heterozygous germline deletions of the last exons of TACSTD1, a gene directly upstream of MSH2 encoding Ep-CAM. Due to these deletions, transcription of TACSTD1 extends into MSH2. The MSH2 promoter in cis with the deletion is methylated in Ep-CAM positive but not in Ep-CAM negative normal tissues, thus revealing a correlation between activity of the mutated TACSTD1 allele and epigenetic inactivation of the corresponding MSH2 allele. Gene silencing by transcriptional read-through of a neighboring gene in either sense, as demonstrated here, or antisense direction, could represent a general mutational mechanism. Depending on the expression pattern of the neighboring gene that lacks its normal polyadenylation signal, this may cause either generalized or mosaic patterns of epigenetic inactivation.
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“In these cases, the abnormal DNA methylation of the gene under investigation was linked to a mutation in a neighboring gene that removed the transcription termination signal (Fig. 1b).”
From A critical view on transgenerational epigenetic inheritance in humans (2018) · cites this paper as [16]
In the citing paper
“Several studies14–16 including a recent study by Guéant et al.18 in this journal, have reported the co-segregation of an abnormal DNA methylation pattern (called “epimutation”) with a rare disease in two or more generations of certain families.”
From A critical view on transgenerational epigenetic inheritance in humans (2018) · cites this paper as [16]
In the citing paper
“Most cases of segregation of abnormal DNA methylation patterns in families with rare diseases, however, turned out to be caused by an underlying genetic variant14–16 (see below).”
From A critical view on transgenerational epigenetic inheritance in humans (2018) · cites this paper as [16]
In the citing paper
“As a consequence, transcription from this gene extended into the gene under investigation, causing abnormal promoter methylation and gene silencing.”
From A critical view on transgenerational epigenetic inheritance in humans (2018) · cites this paper as [16]
Citations
Cites
Beighton, P., & Beighton, G. (1997) · Springer eBooks · doi:10.1007/978-1-4471-0925-9_118 · Cited by 3,165
Lynch, H. T., & de la Chapelle, A. (2003) · New England Journal of Medicine · doi:10.1056/nejmra012242 · Cited by 2,240
Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma
Herman, J. G., Umar, A., Polyák, K., Graff, J. R., Ahuja, N., Issa, J. J., Markowitz, S. D., Willson, J. K. V., Hamilton, S. R., Kinzler, K. W., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.12.6870 · Cited by 1,887
Kane, M., Loda, M. F., Gaida, G. M., Lipman, J., Mishra, R., Goldman, H., Jessup, J. M., & Kolodner, R. D. (1997) · PubMed · Cited by 1,476
Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA
Yu, W., Gius, D. R., Onyango, P. O., Muldoon‐Jacobs, K., Karp, J. E., Feinberg, A. P., & Cui, H. (2008) · Nature · doi:10.1038/nature06468 · Cited by 801
Tufarelli, C., Stanley, J. A. S., Garrick, D., Sharpe, J. A., Ayyub, H., Wood, W. G., & Higgs, D. R. (2003) · Nature Genetics · doi:10.1038/ng1157 · Cited by 547
Germline epimutation of MLH1 in individuals with multiple cancers
Suter, C. M., Martin, D. I. K., & Ward, R. L. (2004) · Nature Genetics · doi:10.1038/ng1342 · Cited by 475
Inheritance of a Cancer-Associated MLH1 Germ-Line Epimutation
Hitchins, M. P., Wong, J. J. L., Suthers, G., Suter, C. M., Martin, D. I. K., Hawkins, N. J., & Ward, R. L. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa064522 · Cited by 409
Heritable germline epimutation of MSH2 in a family with hereditary nonpolyposis colorectal cancer
Chan, T. L., Yuen, S. T., Kong, C. K., Chan, Y. W., Chan, A. S., Ng, W. F., Tsui, W. Y., Lo, M. W., Tam, W. Y., Li, V. S., et al. (2006) · Nature Genetics · doi:10.1038/ng1866 · Cited by 324
Self-citationNew perspectives on connecting messenger RNA 3′ end formation to transcription
Proudfoot, N. J. (2004) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2004.03.007 · Cited by 285
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Nebot-Bral, L. (2021) · theses.fr (ABES) · doi:10.70675/e1797b79z28d4z4e65zbd29zdc771b604d21
Cell mechanics contribution to crypt-villus axis development and maintenance
Soleilhac, M. (2024) · theses.fr (ABES) · doi:10.70675/298c6b66z88a6z4a34z9437zf6ee84c0f295
EpCAM sustains crypt mechanics and prevents aberrant remodelingPreprint
Soleilhac, M., Ruiz, L., Berrebi, D. D., Barai, A., Lecouffe, B., Richelme, S., Obino, V., Dang, T., Buzhinsky, N., Rico, F., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.04.27.721034
Bläker, H., & Höhn, A. K. (2026) · Die Pathologie · doi:10.1007/s00292-026-01562-x
Facon, C., Vermaut, C., Delattre, L., Flament, C., Dardenne, A., Brahimi, A., Lejeune, S., Cattan, S., Bonnet, F., Basset, N., et al. (2026) · Human Mutation · doi:10.1155/humu/6909313
Bassaneze, T., Ferreira, F. O., Sandoval, R. L., Pisani, J. P., Quirino, C. V., de Nicola, P. D. R., Achatz, M. I., Dominguez–Valentin, M., & Rossi, B. M. (2026) · JCO Global Oncology · doi:10.1200/go-25-00708
Reinhardt, L. S., Coster, A., Burnard, S. M., Romanis, C. S., Ziolkowski, A., Pecenpetelovska, G., Mathe, A., Hedley, A., Maltby, V. E., Lechner-Scott, J., et al. (2026) · Journal of Medical Genetics · doi:10.1136/jmg-2026-111541
Rodrigues, P., Matos, P., Gonçalves, J., & Jordan, P. (2026) · Biomedicines · doi:10.3390/biomedicines14061312
Odintsov, I., Nowak, J. A., Baranov, E., Alcindor, T., Haddox, C. L., Venkataraman, V., Sholl, L. M., George, S., Doyle, L. A., Redston, M. S., et al. (2026) · The American Journal of Surgical Pathology · doi:10.1097/pas.0000000000002579
Fish Consumption and Colorectal Neoplasms among Lynch Syndrome Carriers
Bulbaai, M. T., Wesselink, E., Bisseling, T. M., Koornstra, J. J., van Leerdam, M. E., Marchand, L. L., Newcomb, P. A., Samadder, N. J., Schep-Wijnveen, H. J. M., Kampman, E., et al. (2026) · Journal of Nutrition · doi:10.1016/j.tjnut.2026.101670
Ahadova, A., Fayyaz, F., Grez, L. M., Bläker, H., & Kloor, M. (2026) · Familial Cancer · doi:10.1007/s10689-026-00593-w
Exosome-Based Drug Delivery Systems in Colorectal Cancer: Current Evidence and Future Perspectives
da Silva, L. H. D., Floriano, J. F., & Chorilli, M. (2026) · The AAPS Journal · doi:10.1208/s12248-026-01301-3
Updates in the Molecular Biology and Personalized Management of Lynch Syndrome
Lee, D. J., & Yurgelun, M. B. B. (2026) · Gastroenterology Clinics of North America · doi:10.1016/j.gtc.2026.07.004
Molecular mechanisms of promoter silencing by transcriptional readthrough
Shipman, G. A., Walback, E., González, A. G., Horth, C., Gravel, M., Bareke, E., & Majewski, J. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.118139
Redefining the EPCAM Phenotype: Deletion Architecture Determines Lynch Syndrome Cancer Risk
Kohler, K. M., Marsh, A. P. L., Hernandez, F., Horton, C., Rañola, J. M. O., Hampel, H., & Hall, M. J. (2026) · JCO Precision Oncology · doi:10.1200/po-26-00974
The interplay between genetics and epigenetics in colorectal cancer
Derks, S. (2009) · Research Publications (Maastricht University) · doi:10.26481/dis.20091002sd
Seguí, N. (2014) · Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona)
Metadata
- Authors
- Ligtenberg, M. J. L., Kuiper, R. P., Chan, T. L., Goossens, M., Hebeda, K. M., Voorendt, M., Lee, T. Y. H., Bodmer, D., Hoenselaar, E., Hendriks-Cornelissen, S. J. B., Tsui, W. Y., Kong, C. K., Brunner, H. G., van Kessel, A. G., Yuen, S. T., van Krieken, J. H. J. M., Leung, S. Y., & Hoogerbrugge, N.
- Affiliations
- Radboud University Medical Center (NL)
- Queen Mary Hospital (CN)
- Yan Chai Hospital (HK)
- Corresponding author
- Ligtenberg, Marjolijn J L
- Leung, Suet Yi
- ORCID
- Venue
- Nature Genetics
- Published
- 2008-12-21
- Volume
- 41
- Issue
- 1
- Pages
- 112-117
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W1972254989
- Cited by
- 818
- References
- 25
- Citations by year
- 2026: 19 · 2025: 34 · 2024: 38 · 2023: 45 · 2022: 34 · 2021: 41 · 2020: 59 · 2019: 44 · 2018: 54 · 2017: 51 · 2016: 56 · 2015: 46 · 2014: 59 · 2013: 71 · 2012: 49
- FWCI
- 27.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- Lynch syndrome, MSH2, EpCAM, germline deletion, read-through transcription, epigenetic silencing, mismatch repair genes, colorectal cancer, endometrial cancer, polyadenylation signal, gene silencing
- MeSH terms
- Epithelial Cell Adhesion Molecule, Adolescent, Adult, Alleles, Antigens, Neoplasm, Base Sequence, China, Colorectal Neoplasms, Hereditary Nonpolyposis, Exons, Family, Female, Humans, Male, Middle Aged, Molecular Sequence Data, Netherlands, Pedigree, Promoter Regions, Genetic, Cell Adhesion Molecules, Open Reading Frames, Sequence Deletion, DNA Methylation, Inheritance Patterns, White People, Asian People, MutS Homolog 2 Protein, Microsatellite Instability
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