March 15, 2016

Genomic diversity of metastases among men with prostate cancer

At a Glance

  • A genomic analysis found that prostate cancer metastases differed greatly between men, but not within individuals.
  • The finding suggests that a single metastasis within a man can often provide molecular information to help guide therapy.
Older men socializing While most prostate cancers grow very slowly and don’t become life-threatening, prostate cancer that's spread can be difficult to treat. Fuse/Thinkstock

Prostate cancer is the second most common cancer in men in the United States. The prostate is a gland that makes fluid that forms part of semen. Lying just below the bladder in front of the rectum, it surrounds the urethra—the tube that carries urine and semen through the penis and out of the body.

Prostate cancer often has no early symptoms and usually grows very slowly. More than half of prostate cancers remain localized to the prostate and don’t become life-threatening.

Prostate cancer that’s spread (metastasized) is usually treated with radiation or surgery, often along with drugs that block the hormones the tumors rely on to grow and spread. The disease, however, almost always progresses from this stage at some point. These metastatic castration-resistant prostate cancers (mCRPC) have a spectrum of molecular aberrations. Some of the mutations make the cancer cells vulnerable to targeted drugs. The emerging field of precision oncology involves identifying molecular alterations in tumors that make them susceptible to specific drugs.

The success of such precision approaches requires that most or all tumor cells in a person have the same targeted molecular vulnerability. Recent studies have uncovered a remarkable genetic heterogeneity within many primary tumors. These tumors are usually treated with surgery or radiation, which don’t depend on specific molecular vulnerabilities. The genetic diversity of metastases within an individual, however, are largely unknown.

A team led by Dr. Peter S. Nelson at Fred Hutchinson Cancer Research Center in Seattle examined the molecular diversity of 171 tumors taken from 63 men with mCRPC. The extensive analysis included genomic copy number alterations, known oncogenic drivers (mutations tied to cancer), and gene expression. The study was funded by NIH’s National Cancer Institute (NCI). Results appeared online on February 29, 2016, in Nature Medicine.

The researchers observed some alterations that recurred in tumors across the men, but overall there was substantial genomic diversity among tumors from different men. In contrast, there was limited diversity among metastases within an individual. The driver aberrations identified in representative tumors from each man were generally shared by all the tumors in that individual.

These findings suggest that, in most cases, a single biopsy of a prostate cancer metastasis can usually provide useful molecular information to help guide therapy.

“If you look in multiple metastases within a given patient, they're actually very, very similar,” Nelson says. “They're not identical, but in terms of the key features of a cancer that would inform how best to treat that cancer we can feel generally confident, at least with prostate carcinoma, that if you did sample a single tumor, you could make clinical decisions based on what you find.”

This strategy has yet to be tested for its potential for guiding therapy.

—by Harrison Wein, Ph.D.

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Reference: Substantial interindividual and limited intraindividual genomic diversity among tumors from men with metastatic prostate cancer. Kumar A, Coleman I, Morrissey C, Zhang X, True LD, Gulati R, Etzioni R, Bolouri H, Montgomery B, White T, Lucas JM, Brown LG, Dumpit RF, DeSarkar N, Higano C, Yu EY, Coleman R, Schultz N, Fang M, Lange PH, Shendure J, Vessella RL, Nelson PS. Nat Med. 2016 Feb 29. doi: 10.1038/nm.4053. [Epub ahead of print]. PMID: 26928463.

Funding: NIH’s National Cancer Institute (NCI).