黑料吃瓜资源

Cold Spring Harbor, NY — The facts about prostate cancer can be confusing. It鈥檚 the third most common cancer type among Americans—161,000 men will be diagnosed this year, the National Cancer Institute estimates. Yet according to the NCI, 98.6% will be alive in 5 years.

While it鈥檚 often not lethal, prostate cancer still kills lots of men—21,000 this year—because it鈥檚 so common. Many of its victims have metastatic disease at the time of diagnosis; their cancer has already spread. Can we catch potentially lethal cancers earlier to save some of these men?

This week, a team at 黑料吃瓜资源 (CSHL) publishes encouraging results of a pilot study testing a new way of pinpointing the minority who have aggressive disease at the time of diagnosis, a fact that usually determines whether they will have surgery or not. Current procedure calls for a predictive diagnostic biopsy, in which a needle is inserted into the organ at various locations, sometimes guided by MRI and ultrasound.

The new method, which is proposed as a way of augmenting pre-surgical biopsy results, not replacing them, uses advanced genomic tools to analyze what doctors call 鈥渂iopsy cores.鈥� In standard diagnostic biopsies, pathologists examine the tissue collected in these cores, usually a dozen, and assign an overall grade called a Gleason score, based on changes in glandular architecture. A score of 6 or lower is usually interpreted to mean a cancer is slow-growing or 鈥渋ndolent.鈥� Yet some men with borderline Gleason scores undergo surgery and are found to have aggressive cancers. Other times, men with high Gleason scores are found to have indolent cancers upon surgery.

The newly tested method, devised by CSHL Professor Michael Wigler and Associate Professor Alexander Krasnitz, draws the raw material for further analysis from the standard pre-surgical biopsy. The team sequences the genomes of several hundred single cells sampled from each patient鈥檚 diagnostic biopsy cores. They search for certain patterns—for the presence of DNA disturbances called copy-number variations (CNVs). Using computational methods to compare CNV patterns, the team looks for cells whose CNV profiles harbor the same irregularities. This is a sign of clonality. Cancerous tumors are composed of clonal cells—genetically aberrant cells that derive from a single wayward ancestor.

The CSHL method assigns a number to each set of biopsy cores, based on how many of the cores contain clonal cells, how many clonal cells each contains, and how far such cells have dispersed within the prostate. In tests on 8 patients based on collaborations with NYU and Cornell University medical centers, the CSHL testing method yielded assessments of tumors that more closely matched the verdict of post-surgical pathological analysis (which reveal actual pathology) than the corresponding pre-surgical predictive biopsies, according to first author Joan Alexander, M.D.

鈥淭his is important because treatment decisions in such cases depend on the pre-surgical biopsy, not the surgical specimen,鈥� Krasnitz comments. 鈥淲e think single-cell analysis could potentially augment traditional biopsy-core histopathology, significantly improving risk assessment and informing treatment decisions, especially in borderline cases.鈥�

Written by: Peter Tarr, Senior Science Writer | [email protected] | 516-367-8455

Funding

Simons Foundation; National Cancer Institute; Department of the Army; Global Prostate Cancer Research Foundation; Long Island Cruizin鈥� for a Cure

Citation

Alexander J et al, 鈥淯tility of single cell genomics in diagnostic evaluation of prostate cancer鈥� was published online in Cancer Research November 27, 2017.