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The landscape of somatic copy-number alteration across human cancers
Open accessAbstract
A powerful way to discover key genes with causal roles in oncogenesis is to identify genomic regions that undergo frequent alteration in human cancers. Here we present high-resolution analyses of somatic copy-number alterations (SCNAs) from 3,131 cancer specimens, belonging largely to 26 histological types. We identify 158 regions of focal SCNA that are altered at significant frequency across several cancer types, of which 122 cannot be explained by the presence of a known cancer target gene located within these regions. Several gene families are enriched among these regions of focal SCNA, including the BCL2 family of apoptosis regulators and the NF-kappaBeta pathway. We show that cancer cells containing amplifications surrounding the MCL1 and BCL2L1 anti-apoptotic genes depend on the expression of these genes for survival. Finally, we demonstrate that a large majority of SCNAs identified in individual cancer types are present in several cancer types.
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“More recently, it was found that increased expression of the serine synthesis enzyme phosphoglycerate dehydrogenase (PHGDH) in some cancers can result from copy number gain of a region on chromosome 1p (Beroukhim et al., 2010; Locasale et al., 2011; Possemato et al., 2011) or a consequence of oncogenic signaling, including NRF2 and ATF4 signaling (DeNicola et al., 2015), or hypoxia responses (Sam”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Beroukhim et al., 2010
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“Copy number alterations at 4q21 occur in breast cancer (Beroukhim et al., 2010) and engulf fifteen genes in the amplification peak, including CXCL1-8.”
From A CXCL1 Paracrine Network Links Cancer Chemoresistance and Metastasis (2012) · cites this paper as Beroukhim et al., 2010
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Metadata
- Authors
- Beroukhim, R., Mermel, C. H., Porter, D., Wei, G., Raychaudhuri, S., Donovan, J., Barretina, J., Boehm, J. S., Dobson, J., Urashima, M., Mc Henry, K. T., Pinchback, R. M., Ligon, A. H., Cho, Y.-J., Haery, L., Greulich, H., Reich, M., Winckler, W., Lawrence, M. S., Weir, B. A., Tanaka, K. E., Chiang, D. Y., Bass, A. J., Loo, A., Hoffman, C., Prensner, J., Liefeld, T., Gao, Q., Yecies, D., Signoretti, S., Maher, E., Kaye, F. J., Sasaki, H., Tepper, J. E., Fletcher, J. A., Tabernero, J., Baselga, J., Tsao, M.-S., Demichelis, F., Rubin, M. A., Janne, P. A., Daly, M. J., Nucera, C., Levine, R. L., Ebert, B. L., Gabriel, S., Rustgi, A. K., Antonescu, C. R., Ladanyi, M., Letai, A., Garraway, L. A., Loda, M., Beer, D. G., True, L. D., Okamoto, A., Pomeroy, S. L., Singer, S., Golub, T. R., Lander, E. S., Getz, G., Sellers, W. R., & Meyerson, M.
- Affiliations
- Broad Institute (US)
- Jikei University School of Medicine (JP)
- Brigham and Women's Hospital (US)
- Boston Children's Hospital (US)
- Dana-Farber Cancer Institute (US)
- The University of Texas Southwestern Medical Center (US)
- Walter Reed National Military Medical Center (US)
- Nagoya City University (JP)
- University of North Carolina at Chapel Hill (US)
- Universitat Autònoma de Barcelona (ES)
- University Health Network (CA)
- Weill Cornell Medicine (US)
- Beth Israel Deaconess Medical Center (US)
- Memorial Sloan Kettering Cancer Center (US)
- Abramson Cancer Center (US)
- University of Michigan (US)
- University of Washington Medical Center (US)
- Corresponding author
- Lander, Eric S.
- Getz, Gad
- Sellers, William R.
- Meyerson, Matthew
- ORCID
- Beroukhim, Rameen
- Mermel, Craig H.
- Raychaudhuri, Soumya
- Donovan, Jerry
- Barretina, Jordi
- Boehm, Jesse S.
- Urashima, Mitsuyoshi
- Ligon, Azra H.
- Cho, Yoon-Jae
- Greulich, Heidi
- Reich, Michael
- Winckler, Wendy
- Lawrence, Michael S.
- Tanaka, Kumiko E.
- Chiang, Derek Y.
- Bass, Adam J.
- Hoffman, Carter
- Prensner, John
- Liefeld, Ted
- Gao, Qing
- Yecies, Derek
- Signoretti, Sabina
- Maher, Elizabeth
- Kaye, Frederic J.
- Tepper, Joel E.
- Fletcher, Jonathan A.
- Tabernero, Josep
- Tsao, Ming-Sound
- Demichelis, Francesca
- Rubin, Mark A.
- Janne, Pasi A.
- Daly, Mark J.
- Nucera, Carmelo
- Levine, Ross L.
- Ebert, Benjamin L.
- Gabriel, Stacey
- Rustgi, Anil K.
- Antonescu, Cristina R.
- Ladanyi, Marc
- Letai, Anthony
- Garraway, Levi A.
- Loda, Massimo
- Beer, David G.
- True, Lawrence D.
- Okamoto, Aikou
- Pomeroy, Scott L.
- Singer, Samuel
- Golub, Todd R.
- Lander, Eric S.
- Getz, Gad
- Sellers, William R.
- Meyerson, Matthew
- Venue
- Nature
- Published
- 2010-02
- Volume
- 463
- Issue
- 7283
- Pages
- 899-905
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2826709
- OpenAlex
- W2153056550
- Cited by
- 4,017
- References
- 98
- Citations by year
- 2026: 160 · 2025: 215 · 2024: 268 · 2023: 257 · 2022: 266 · 2021: 287 · 2020: 283 · 2019: 222 · 2018: 278 · 2017: 261 · 2016: 253 · 2015: 262 · 2014: 232 · 2013: 278 · 2012: 221
- FWCI
- 77.79
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
- Institutional Research Information System (Università degli Studi di Trento) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Human Genome Research Institute (U54HG003067)
- National Cancer Institute (P50CA90578, K08CA134931, R01CA109038, P01CA098101, P01CA085859, U24CA126546, R01CA109467, P50CA090578, K08CA122833)
- National Institute of General Medical Sciences (T32GM007753)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (K08AR055688)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- somatic copy number alterations, focal copy number alterations, cancer genomics, Mcl-1, Bcl-xL, Bcl-2 family proteins, apoptosis, NF-κB signaling, anti-apoptotic genes, oncogene amplification, fragile sites, homozygous deletion, hemizygous deletion
- MeSH terms
- Cell Survival, Gene Amplification, Multigene Family, Humans, Neoplasms, Signal Transduction, Apoptosis, Gene Dosage, Proto-Oncogene Proteins c-bcl-2, Genomics, Cell Line, Tumor, bcl-X Protein, DNA Copy Number Variations, Myeloid Cell Leukemia Sequence 1 Protein
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