The landscape of somatic copy-number alteration across human cancers

By Rameen Beroukhim, Craig H. Mermel, D. Porter, G. Wei, Soumya Raychaudhuri, Jerry Donovan, J. Barretina, J. Boehm, Jennifer Dobson, M. Urashima and 52 more. Nature, 2010

3,892 citations recorded by the source corpus.

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-κΒ 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.

Subfields: Cancer Research, Genetics, Pathology and Forensic Medicine

View Paper: https://www.semanticscholar.org/paper/31bb581bccd676268e50ea4c18a970deec9514de

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Citations in the corpus

The Life History of 21 Breast Cancers (2012, background): “Trisomy 1q is one of the commonest copy number alterations seen in breast cancer (Beroukhim et al., 2010; Bignell et al., 2010).”
Lengthening and shortening of plasma DNA in hepatocellular carcinoma patients (2015, background): “CNA involving a whole chromosome arm or a large trunk of a chromosome arm is relatively common (35).”
GISTIC2.0 facilitates sensitive and confident localization of the targets of focal somatic copy-number alteration in human cancers (2011, methodology): “GISTIC has been applied to multiple cancer types, including glioblastoma [10,15], lung adenocarcinoma [16], melanoma [17], colorectal carcinoma [18], hepatocellular carcinoma [19], ovarian carcinoma [20], medulloblastoma [21], and lung and esophageal squamous carcinoma [22], and has helped identify ”
MYC on the Path to Cancer (2012, background): “MYC is frequently translocated in multiple myeloma (Shou et al., 2000) and is one of the most highly amplified oncogenes among many different human cancers (Beroukhim et al., 2010).”
Transcriptional Addiction in Cancer (2017, positive): “Thus, the majority of human cancers exhibit genetic amplification or transcriptional dysregulation of MYC, which is accompanied by an anabolic transcriptional response driving proliferation and metabolic adaptation (Beroukhim et al., 2010).”
Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development (2011, background): “(D) Genome-wide profile of rearrangements from the same patient 31 months later, at relapse after therapy. of which 80% were primary tumors (Beroukhim et al., 2010), we find evidence for chromothripsis in a similar proportion of cases (Figure S1T).”
Replication stress and cancer (2015, neutral): “Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint.”
An Integrated Approach to Uncover Drivers of Cancer (2010, methodology): “…been collected for thousands of tumors at high resolution using array comparative genomic hybridization (aCGH) (Pinkel et al., 1998), high-density single-nucleotide polymorphism (SNP) microarrays (Beroukhim et al., 2010; Lin et al., 2008), and massively parallel sequencing (Pleasance et al., 2010).”