Integrative genomic profiling of human prostate cancer

Description: GEO SuperSeries of expression profiling of prostatic neoplasms.
This SuperSeries is composed of the SubSeries GSE21034, GSE21035, and GSM525577. Each one concerns measuring prostate cancer genomes and different arrays of expression data, including DNA copy number, mRNA and microRNA. The prostate tumor samples originated from 218 patients.

Each dataset in the SubSeries share the same description: "Current knowledge of prostate cancer genomes is largely based on relatively small patient cohorts using single modality analysis platforms. Here we report concordant assessment of DNA copy number, mRNA and microRNA expression and focused exon resequencing in prostate tumors from 218 patients with primary or metastatic prostate cancer with a median of 5 years clinical follow-up, now made available as a public resource. Mutations in known, commonly mutated oncogenes and tumor suppressor genes such as PIK3CA, KRAS, BRAF and TP53 are present but generally rare. However, integrative analysis of mutations with copy number alterations (CNAs) and expression changes reveal alterations in the PI3K, RAS/RAF and androgen receptor (AR) pathways in nearly all metastatic samples and in a higher frequency of primary samples than previously suspected based on single-gene studies. Other new findings include evidence that the nuclear receptor coactivator NCOA2 functions as a driver oncogene in ~20 percent of primaries. Tumors with the androgen-driven TMPRSS2-ERG fusion were significantly associated with a small, previously unrecognized, prostate-specific 3p14 deletion that, through mRNA expression and resequencing analysis, implicates FOXP1, RYBP and SHQ1 as candidate cooperative tumor suppressors. Comparison of transcriptome and DNA copy number data from primary tumors for prognostic impact revealed that CNAs robustly define clusters of low- and high-risk disease beyond that achieved by Gleason score. In sum, this integrative genomic analysis of a substantial cohort of tumors clarifies the role of several known cancer pathways in prostate cancer, implicates several new ones, reveals a previously unappreciated role for CNAs in prognosis and provides a blueprint for clinical development of pathway inhibitors."

Subject of Study

Homo sapiens

Subject(s)

Mutation

Prostatic Neoplasms

OncoTree Cancer Type(s)

Prostate

Access via GEO
CEL and plain text sequencing data.
Accession #: GSE21032

Access via BioProject
Additional information about overall initiative.
Accession #: PRJNA126455
Access Restrictions: Free to All
Access Instructions: The NCBI Gene Expression Omnibus, SRA, and BioProject databases provide open access to these files.
Associated Publications: Adams E, Karthaus W, Hoover E, et al. FOXA1 mutations alter pioneering activity, differentiation and prostate cancer phenotypes. Nature. 2019; 571(7765):408-412.

Taylor B, Schultz N, Hieronymus H, et al. Integrative genomic profiling of human prostate cancer. Cancer Cell. 2010; 18(1):11-22.
Data Type: Genomic
Equipment Used: Affymetrix Human Exon 1.0 ST Array

Human Genome CGH Microarray 244A

Human miRNA Microarray 2.0 G4470B
Software Used: GEO2R
Use GEO2R to compare two or more groups of Samples in order to identify genes that are differentially expressed across experimental conditions. Results are presented as a table of genes ordered by significance.
Dataset Format(s): Plain Text, TAR, CEL
Dataset Size: 24.2 Gb (TAR of CEL, TXT)

Data Catalog Record Updated: 2023-11-28