Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Molecular Profiling of Metastatic Prostate Carcinoma Reveals Substantial Inter-individual and Limited Intra-individual Diversity: Implications for Precision Oncology

ABSTRACT: Prostate cancers exhibit a spectrum of molecular aberrations of which a substantial subset are amenable to targeted therapeutics. To determine the diversity of somatic alterations present in metastasis within and between individuals we characterized the genomic landscapes of 176 tumors acquired from 63 men. In contrast to the considerable variation across individuals, the molecular diversity of tumors within an individual was substantially less: alterations in putative drivers of cancer growth and cell cycle progression status were highly concordant. While androgen receptor activity was inversely related to proliferation, the expression of Fanconi Anemia complex genes was strongly associated with increased cell cycle progression. Inhibition of FANCA, FANCC, FANCD2 and BRCA2 expression reduced prostate cancer growth. The limited molecular diversity across metastases may result from bottlenecks imposed by the dissemination process, limited evolutionary time between metastatic seeding and tumor sampling, intermixing of tumor clones, and selection resulting from treatment pressures. Though exceptions exist, evaluating a single metastasis provides a reasonable assessment of the key molecular processes that occur throughout the spectrum of disseminated tumors within an individual, and may be used for selecting treatments based on predicted molecular vulnerabilities. Custom Agilent 44K whole human genome expression oligonucleotide microarrays were used to profile 171 CRPC tumors from 63 patients. RNA was amplified prior to hybridization against a common reference pool of prostate tumor cell lines.

ORGANISM(S): Homo sapiens

SUBMITTER: Ilsa Coleman

PROVIDER: E-GEOD-74685 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Epithelial mesenchymal-like transition occurs in a subset of cells in castration resistant prostate cancer bone metastases.

Haider Maahum M Zhang Xiaotun X Coleman Ilsa I Ericson Nolan N True Lawrence D LD Lam Hung-Ming HM Brown Lisha G LG Ketchanji Melanie M Nghiem Belinda B Lakely Bryce B Coleman Roger R Montgomery Bruce B Lange Paul H PH Roudier Martine M Higano Celestia S CS Bielas Jason H JH Nelson Peter S PS Vessella Robert L RL Morrissey Colm C

Clinical & experimental metastasis 20151214 3

TGFβ is a known driver of epithelial-mesenchymal transition (EMT) which is associated with tumor aggressiveness and metastasis. However, EMT has not been fully explored in clinical specimens of castration-resistant prostate cancer (CRPC) metastases. To assess EMT in CRPC, gene expression analysis was performed on 149 visceral and bone metastases from 62 CRPC patients and immunohistochemical analysis was performed on 185 CRPC bone and visceral metastases from 42 CRPC patients. In addition, to ass ...[more]

PMID: 26667932

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Dataset Information

Molecular Profiling of Metastatic Prostate Carcinoma Reveals Substantial Inter-individual and Limited Intra-individual Diversity: Implications for Precision Oncology

Publications

Epithelial mesenchymal-like transition occurs in a subset of cells in castration resistant prostate cancer bone metastases.

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