( llaboration involving DePinho's Dana-Fa...)Scientists discover new genetic subtypes of common blood cancer

llaboration involving DePinho's Dana-Farber group, Cameron Brennan, MD, of Memorial Sloan-Kettering Cancer Center, and John Shaughnessy, MD, of the Myeloma Institute for Research and Therapy at the University of Arkansas for Medical Sciences. Lead authors are Daniel Carrasco, MD, PhD, and Giovanni Tonon, MD, PhD, of Dana-Farber, and Yongsheng Huang, MS, of the Myeloma Institute for Research and Therapy at the University of Arkansas for Medical Science.

Myeloma cells' genomes are scenes of rampant chaos: extra or missing chromosomes; pieces of broken chromosomes randomly reattached; genes that are mutated or amplified ?present in too many copies ?or are overexpressed or absent. The roles played by these myriad abnormalities in the initiation and progression of myeloma are only beginning to be understood, but it's been observed that different abnormalities are often found from one patient to the next.

Previously, scientists had identified two genetic subtypes of myeloma. One, called hyperdiploid MM, is characterized by extra copies of entire chromosomes, and patients with this subtype appear to fare better. The non-hyperdiploid form lacks these extra chromosomes and instead has abnormal rearrangements between different chromosomes, and the outlook is generally worse for these patients.

The collaborating researchers sought to cast a wide net to capture as many of the genetic flaws in myeloma cells as possible, creating a comprehensive atlas of this cancerous genome. First, they used a technique called high-resolution array CGH (comparative genomic hybridization) to analyze samples from 67 newly diagnosed patients provided by Shaughnessy in Arkansas. The CGH technique compared the genomes of a normal blood cell with various myeloma cells in search of differences. The goal was to identify recurrent copy number alterations ?hotspots on the chromosomes where genes were abnormally duplicated or lost across many different tumors.

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Source:Dana-Farber Cancer Institute

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