Pan-cancer patterns of somatic copy-number alteration

By Travis Zack, S. Schumacher, Scott L. Carter, A. Cherniack, G. Saksena, B. Tabak, M. Lawrence, Cheng-Zhong Zhang, J. Wala, Craig H. Mermel and 8 more. Nature Genetics, 2013

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Determining how somatic copy number alterations (SCNAs) promote cancer is an important goal. We characterized SCNA patterns in 4,934 cancers from The Cancer Genome Atlas Pan-Cancer data set. Whole-genome doubling, observed in 37% of cancers, was associated with higher rates of every other type of SCNA, TP53 mutations, CCNE1 amplifications and alterations of the PPP2R complex. SCNAs that were internal to chromosomes tended to be shorter than telomere-bounded SCNAs, suggesting different mechanisms underlying their generation. Significantly recurrent focal SCNAs were observed in 140 regions, including 102 without known oncogene or tumor suppressor gene targets and 50 with significantly mutated genes. Amplified regions without known oncogenes were enriched for genes involved in epigenetic regulation. When levels of genomic disruption were accounted for, 7% of region pairs were anticorrelated, and these regions tended to encompass genes whose proteins physically interact, suggesting related functions. These results provide insights into mechanisms of generation and functional consequences of cancer-related SCNAs.

Subfields: Cancer Research, Genetics, Pathology and Forensic Medicine

View Paper: https://www.semanticscholar.org/paper/c9e247f6ec9ccd1852690deb8da49386feb687b5

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Citations in the corpus

Comprehensive analyses of tumor immunity: implications for cancer immunotherapy (2016, methodology): “The percentage of total DNA for each tumor was estimated using DNA methylation data as previously described and compared with purity estimates derived from SNP data [20, 37].”
From Krebs to Clinic: Glutamine Metabolism to Cancer Therapy (2016, neutral): “BPTES inhibition of hGA(124-551), a truncated form of human kidneytype glutaminase.”
Integrative Analysis Identifies Four Molecular and Clinical Subsets in Uveal Melanoma. (2018, methodology): “…NA https://CRAN.R-project.org/package=heatmap.plus ImageMagick www.imagemagick.org In Silico Admixture Removal (ISAR) Zack et al., 2013 Integrative Genomics Viewer (IGV) Thorvaldsdottir et al., 2013 http://software.broadinstitute.org/software/igv/ Maftools Mayakonda…”
Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer. (2018, neutral): “As observed in a previous pancancer analysis, chromothripsis was not associated with an 6 Cell 174, 1–12, July 26, 2018 elevated mutation frequency genomewide (p > 0.05, Figure 3E) (Zack et al., 2013).”
DNA replication stress as a hallmark of cancer. (2015, background): “Of the top 49 recurrent internal chromosomal deletions, 21 target one of the 100 largest genes in the human genome (11).”
TSGene 2.0: an updated literature-based knowledgebase for tumor suppressor genes (2015, background): “The inactivation or reduced function of protein-coding TSGs can be induced in many ways including promoter methylation changes (4), copy number alterations (5), deregulated mRNA expression due to microRNA (miRNA) activities (6) and competing endogenous long non-coding RNAs (lncRNAs) (7).”
The Cancer Genome Atlas (TCGA): an immeasurable source of knowledge (2015, background): “Furthermore, Zack et al. expanded cancer studies to somatic copy number alteration (SCNA) patterns, delivering insights into mechanisms of generation and functional consequences of cancer-related SCNAs [79].”