GENOMIC ANALYSIS OF PROSTATE CANCER ONLINE

June 30 2010 — In what its creators call a "unique public resource for the cancer research community," a genomic analysis of prostate cancer is now available online.

The immediate significance of this resource stems from the fact that the disease has a "high prevalence" and there is a "relative paucity of large comprehensive genomic datasets in prostate cancer," according to the authors of a review of the analysis published online June 24 in Cancer Cell.

There might be future significance as well, suggest the authors.

Other projects that characterize genomes for glioblastoma, lung, colon, pancreas, and breast cancers have "provided critical insights into the molecular classification of cancers" write the authors, led by Barry Taylor, PhD, from Memorial Sloan-Kettering Cancer Center in New York City.

These other projects have led to improvements in patient care and create a hope for the same in prostate cancer, suggested one of the study's other authors.

"Genomic studies in other cancer types have resulted in new drug targets and strategies to classify patients into clinically meaningful subgroups that improve treatment decisions," said coauthor Charles Sawyers, MD, PhD, in a press statement. "This first-ever database of its type brings us one step closer to achieving that goal in prostate cancer." Dr. Sawyers is from the Howard Hughes Medical Institute in Chevy Chase, Maryland.

The authors note that there have been fewer genomic studies in prostate cancer than in some other tumor types, in part because of the "special challenges" of prostate cancer, including the "relatively small tumor size and admixture with stroma that requires careful pathologist-guided dissection."

No Common Mutation

The new analysis used 218 primary and metastatic prostate cancer samples and 12 cell lines and xenografts. The samples were obtained from patients treated with radical prostatectomy at Memorial Sloan-Kettering. There was a 5-year median follow-up with the tumor set, which allowed the authors to attempt to address matters of prognosis using the various data.

The investigators defined transcriptomes, copy-number alterations, and exon resequencing and/or focused mutation detection for 157 "high-interest" genes.

One of the observations from the exon resequencing data is that somatic point mutations in prostate cancer might be rare relative to other tumor types, such as lung cancer and melanoma. "No single gene emerged as commonly mutated," write the authors.

Also, mutations in commonly mutated oncogenes and tumor suppressor genes, such as PIK3CA, KRAS, BRAF, and TP53, are present but rare, say the authors.

Nonetheless, an integrative analysis of mutations, copy-number alterations, and expression changes revealed changes in the PI3K, RAS/RAF, and androgen-receptor pathways in nearly all metastatic samples and a high frequency of primary samples, report the authors.

Finding such alterations in primary tumors — and not just metastatic tumors, as expected — extends the "potential importance of androgen-receptor pathway perturbation to disease initiation."

Dr. Sawyers summarized a number of the findings. "These data clarify the role of several known cancer pathways and provide important clues into others. We have gained insight into the importance of androgen-receptor status."

The genomic-profiling project is dedicated to the memory of Memorial Sloan-Kettering researcher William Gerald, who initiated it.

The research was supported in part by a Memorial Sloan-Kettering Cancer Center Prostate SPORE grant and by the David H. Koch Foundation.

Cancer Cell. Published online June 23, 2010. Abstract