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Genome changes tracked during multiple myeloma initiation, progression and treatment

Scientists have made significant progress toward elucidating key genetic events associated with the development and progression of multiple myeloma (MM), an incurable malignancy that is the second most common cancer of the blood. The results, published in the April issue of Cancer Cell, provide new genetic and biological insights that open innovative directions for the discovery of effective therapeutics that can be targeted to specific MM patients based on genetic perturbations known to contribute to MM pathogenesis.

Although genetic screening studies have provided some insight into the pathogenesis that underlies MM, the full landscape of genomic events driving cancer initiation, progression, and response to treatment have remained hidden from view. Drs. Ron A. DePinho from the Dana-Farber Cancer Institute, Cameron Brennan of Memorial Sloan-Kettering Cancer Center, and John Shaughnessy of the Myeloma Institute for Research and Therapy at the University of Arkansas for Medical Sciences and their colleagues performed a high-resolution and integrated analysis of gene copy number alterations and expression profiles of outcome-annotated MM clinical specimens.

The researchers discovered a high level of molecular heterogeneity typified by many new recurrent amplifications and deletions that point to a large number of yet-to-be-discovered oncogenes and tumor suppressor genes. These amplification and deletion patterns define new disease subgroups of MM that are characterized by varied dysregulation of distinct cancer-relevant genes and can be correlated with different clinical outcomes. Importantly, several candidate genes identified in this study possess broad clinical and biological relevance, as they are also associated with histologically unrelated malignancies such as pancreatic, lung, breast, and ovarian cancer and may thus represent a rite of passage for many different cancers.

"This integrated and detailed view of the MM genome is consiste
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Contact: Heidi Hardman
hhardman@cell.com
617-397-2879
Cell Press
10-Apr-2006


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