Copy number and targeted mutational analysis reveals novel somatic events in metastatic prostate tumors

Christiane M. Robbins, Waibov A. Tembe, Angela Baker, Shripad Sinari, Tracy Y. Moses, Stephen Beckstrom-Sternberg, James Beckstrom-Sternberg, Michael Barrett, James Long, Arul Chinnaiyan, James Lowey, Edward Suh, John V. Pearson, David W. Craig, David B. Agus, Kenneth J. Pienta, John D. Carpten

Research output: Contribution to journalArticle

127 Citations (Scopus)

Abstract

Advanced prostate cancer can progress to systemic metastatic tumors, which are generally androgen insensitive and ultimately lethal. Here, we report a comprehensive genomic survey for somatic events in systemic metastatic prostate tumors using both high-resolution copy number analysis and targeted mutational survey of 3508 exons from 577 cancer-related genes using next generation sequencing. Focal homozygous deletions were detected at 8p22, 10q23.31, 13q13.1, 13q14.11, and 13q14.12. Key genes mapping within these deleted regions include PTEN, BRCA2, C13ORF15, and SIAH3. Focal high-level amplifications were detected at 5p13.2-p12, 14q21.1, 7q22.1, and Xq12. Key amplified genes mapping within these regions include SKP2, FOXA1, and AR. Furthermore, targeted mutational analysis of normal-tumor pairs has identified somatic mutations in genes known to be associated with prostate cancer including AR and TP53, but has also revealed novel somatic point mutations in genes including MTOR, BRCA2, ARHGEF12, and CHD5. Finally, in one patient where multiple independent metastatic tumors were available, we show common and divergent somatic alterations that occur at both the copy number and point mutation level, supporting a model for a common clonal progenitor with metastatic tumor-specific divergence. Our study represents a deep genomic analysis of advanced metastatic prostate tumors and has revealed candidate somatic alterations, possibly contributing to lethal prostate cancer.

Original languageEnglish (US)
Pages (from-to)47-55
Number of pages9
JournalGenome Research
Volume21
Issue number1
DOIs
StatePublished - Jan 2011
Externally publishedYes

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Prostate
Neoplasms
Prostatic Neoplasms
Chromosome Mapping
Point Mutation
Neoplasm Genes
Androgens
Genes
Exons
Mutation
Surveys and Questionnaires

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Robbins, C. M., Tembe, W. A., Baker, A., Sinari, S., Moses, T. Y., Beckstrom-Sternberg, S., ... Carpten, J. D. (2011). Copy number and targeted mutational analysis reveals novel somatic events in metastatic prostate tumors. Genome Research, 21(1), 47-55. https://doi.org/10.1101/gr.107961.110

Copy number and targeted mutational analysis reveals novel somatic events in metastatic prostate tumors. / Robbins, Christiane M.; Tembe, Waibov A.; Baker, Angela; Sinari, Shripad; Moses, Tracy Y.; Beckstrom-Sternberg, Stephen; Beckstrom-Sternberg, James; Barrett, Michael; Long, James; Chinnaiyan, Arul; Lowey, James; Suh, Edward; Pearson, John V.; Craig, David W.; Agus, David B.; Pienta, Kenneth J.; Carpten, John D.

In: Genome Research, Vol. 21, No. 1, 01.2011, p. 47-55.

Research output: Contribution to journalArticle

Robbins, CM, Tembe, WA, Baker, A, Sinari, S, Moses, TY, Beckstrom-Sternberg, S, Beckstrom-Sternberg, J, Barrett, M, Long, J, Chinnaiyan, A, Lowey, J, Suh, E, Pearson, JV, Craig, DW, Agus, DB, Pienta, KJ & Carpten, JD 2011, 'Copy number and targeted mutational analysis reveals novel somatic events in metastatic prostate tumors', Genome Research, vol. 21, no. 1, pp. 47-55. https://doi.org/10.1101/gr.107961.110
Robbins CM, Tembe WA, Baker A, Sinari S, Moses TY, Beckstrom-Sternberg S et al. Copy number and targeted mutational analysis reveals novel somatic events in metastatic prostate tumors. Genome Research. 2011 Jan;21(1):47-55. https://doi.org/10.1101/gr.107961.110
Robbins, Christiane M. ; Tembe, Waibov A. ; Baker, Angela ; Sinari, Shripad ; Moses, Tracy Y. ; Beckstrom-Sternberg, Stephen ; Beckstrom-Sternberg, James ; Barrett, Michael ; Long, James ; Chinnaiyan, Arul ; Lowey, James ; Suh, Edward ; Pearson, John V. ; Craig, David W. ; Agus, David B. ; Pienta, Kenneth J. ; Carpten, John D. / Copy number and targeted mutational analysis reveals novel somatic events in metastatic prostate tumors. In: Genome Research. 2011 ; Vol. 21, No. 1. pp. 47-55.
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