The genomic complexity of primary human prostate cancer

By M. Berger, M. Lawrence, F. Demichelis, Y. Drier, Kristian Cibulskis, A. Sivachenko, A. Sboner, Raquel Esgueva, D. Pflueger, C. Sougnez and 31 more. Nature, 2011

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Prostate cancer is the second most common cause of male cancer deaths in the United States. However, the full range of prostate cancer genomic alterations is incompletely characterized. Here we present the complete sequence of seven primary human prostate cancers and their paired normal counterparts. Several tumours contained complex chains of balanced (that is, ‘copy-neutral’) rearrangements that occurred within or adjacent to known cancer genes. Rearrangement breakpoints were enriched near open chromatin, androgen receptor and ERG DNA binding sites in the setting of the ETS gene fusion TMPRSS2–ERG, but inversely correlated with these regions in tumours lacking ETS fusions. This observation suggests a link between chromatin or transcriptional regulation and the genesis of genomic aberrations. Three tumours contained rearrangements that disrupted CADM2, and four harboured events disrupting either PTEN (unbalanced events), a prostate tumour suppressor, or MAGI2 (balanced events), a PTEN interacting protein not previously implicated in prostate tumorigenesis. Thus, genomic rearrangements may arise from transcriptional or chromatin aberrancies and engage prostate tumorigenic mechanisms.

Subfields: Cancer Research, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/e909b7e78460df2e579c030db3897183f0fd1d84

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Citations in the corpus

Absolute quantification of somatic DNA alterations in human cancer (2012, positive): “…and ploidy estimates with expression subtypes and to develop statistical power calculations and use them to select well-powered samples for whole-genome sequencing in several published 22, 23, 24 , and numerous ongoing projects, including breast, prostate, and skin cancer genome characterization.”
Lessons from the cancer genome. (2013, neutral): “Chromosomal Chains A whole-genome sequencing study of primary human prostate cancer (Berger et al., 2011) uncovered a distinct category of complex chromosomal rearrangements.”
Integrative Annotation of Variants from 1092 Humans: Application to Cancer Genomics (2013, background): “Patterns of somatic mutations were obtained from seven prostate cancer (17), three medulloblastoma (20), and 21 breast cancer genomes (19), whereas driver mutations were also identified in additional 57 prostate cancer genomes (18).”
Integrative clinical genomics of advanced prostate cancer (2015, neutral): “Multiple studies have identified recurrent somatic mutations, copy number alterations, and oncogenic structural DNA rearrangements (chromoplexy) in primary prostate cancer (Baca et al., 2013; Barbieri et al., 2012; Berger et al., 2011; Cooper et al., 2015; Pflueger et al., 2011; Taylor et al., 2010;”