Dataset Information

Cells Comprising the Prostate Cancer Microenvironment Lack Recurrent Clonal Somatic Genomic Aberrations.

ABSTRACT:

Unlabelled

Prostate cancer-associated stroma (CAS) plays an active role in malignant transformation, tumor progression, and metastasis. Molecular analyses of CAS have demonstrated significant changes in gene expression; however, conflicting evidence exists on whether genomic alterations in benign cells comprising the tumor microenvironment (TME) underlie gene expression changes and oncogenic phenotypes. This study evaluates the nuclear and mitochondrial DNA integrity of prostate carcinoma cells, CAS, matched benign epithelium and benign epithelium-associated stroma by whole-genome copy-number analyses, targeted sequencing of TP53, and FISH. Array comparative genomic hybridization (aCGH) of CAS revealed a copy-neutral diploid genome with only rare and small somatic copy-number aberrations (SCNA). In contrast, several expected recurrent SCNAs were evident in the adjacent prostate carcinoma cells, including gains at 3q, 7p, and 8q, and losses at 8p and 10q. No somatic TP53 mutations were observed in CAS. Mitochondrial DNA (mtDNA) extracted from carcinoma cells and stroma identified 23 somatic mtDNA mutations in neoplastic epithelial cells, but only one mutation in stroma. Finally, genomic analyses identified no SCNAs, LOH, or copy-neutral LOH in cultured cancer-associated fibroblasts, which are known to promote prostate cancer progression in vivo

Implications

The gene expression changes observed in prostate cancer-adjacent stroma and the attendant contribution of the stroma to the development and progression of prostate cancer are not due to frequent or recurrent genomic alterations in the TME.

SUBMITTER: Bianchi-Frias D

PROVIDER: S-EPMC5582956 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cells Comprising the Prostate Cancer Microenvironment Lack Recurrent Clonal Somatic Genomic Aberrations.

Bianchi-Frias Daniella D Basom Ryan R Delrow Jeffrey J JJ Coleman Ilsa M IM Dakhova Olga O Qu Xiaoyu X Fang Min M Franco Omar E OE Ericson Nolan G NG Bielas Jason H JH Hayward Simon W SW True Lawrence L Morrissey Colm C Brown Lisha L Bhowmick Neil A NA Rowley David D Ittmann Michael M Nelson Peter S PS

Molecular cancer research : MCR 20160111 4

<h4>Unlabelled</h4>Prostate cancer-associated stroma (CAS) plays an active role in malignant transformation, tumor progression, and metastasis. Molecular analyses of CAS have demonstrated significant changes in gene expression; however, conflicting evidence exists on whether genomic alterations in benign cells comprising the tumor microenvironment (TME) underlie gene expression changes and oncogenic phenotypes. This study evaluates the nuclear and mitochondrial DNA integrity of prostate carcinom ...[more]

PMID: 26753621

Similar Datasets

Project description:Simple summarySomatic and germline aberrations in homologous recombinant repair (HHR) genes are associated with increased incidence and poor prognosis for prostate cancer. Through next-generation sequencing of prostate cancer patients across all clinical states from north China, here the authors identified a somatic mutational rate of 3% and a germline mutational rate of 3.9% for HRR genes using 200 tumor tissues and 714 blood specimens. Thus, mutational rates in HRR genes were lower compared with previous studies.BackgroundHomologous recombination repair deficiency is associated with higher risk and poorer prognosis for prostate cancer. However, the landscapes of somatic and germline mutations in these genes remain poorly defined in Chinese patients, especially for those with localized disease and those from north part of China. In this study, we explore the genomic profiles of these patients.MethodsWe performed next-generation sequencing with 200 tumor tissues and 714 blood samples from prostate cancer patients at Peking University First Hospital, using a 32 gene panel including 19 homologous recombination repair genes.ResultsTP53, PTEN, KRAS were the most common somatic aberrations; BRCA2, NBN, ATM were the most common germline aberrations. In terms of HRR genes, 3% (6/200) patients harbored somatic aberrations, and 3.8% (28/714) patients harbored germline aberrations. 98.0% (196/200) somatic-tested and 72.7% (519/714) germline tested patients underwent prostatectomy, of which 28.6% and 42.0% had Gleason scores ≥8 respectively. Gleason scores at either biopsy or prostatectomy were predictive for somatic aberrations in general and in TP53; while age of onset <60 years old, PSA at diagnosis, and Gleason scores at biopsy were clinical factors associated with positive germline aberrations in BRCA2/ATM.ConclusionsOur results showed a distinct genomic profile in homologous recombination repair genes for patients with prostate cancer across all clinical states from north China. Clinicians may consider to expand the prostate cancer patients receiving genetic tests to include more individuals due to the weak guiding role by the clinical factors currently available.

Dataset Information

Cells Comprising the Prostate Cancer Microenvironment Lack Recurrent Clonal Somatic Genomic Aberrations.

Unlabelled

Implications

Publications

Cells Comprising the Prostate Cancer Microenvironment Lack Recurrent Clonal Somatic Genomic Aberrations.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets