SF3B1, with no prior established role in CLL” />

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ASH: Somatic Mutations ID’d in Chronic Lymphocytic Leukemia

Last Updated: December 12, 2011.

 

Mutations identified in nine genes, including SF3B1, with no prior established role in CLL

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Somatic mutations at significant frequencies have been identified in nine genes in patients with chronic lymphocytic leukemia, according to a study published online Dec. 12 in the New England Journal of Medicine to coincide with presentation at the annual meeting of the American Society of Hematology, held from Dec. 10 to 13 in San Diego.

MONDAY, Dec. 12 (HealthDay News) -- Somatic mutations at significant frequencies have been identified in nine genes in patients with chronic lymphocytic leukemia, according to a study published online Dec. 12 in the New England Journal of Medicine to coincide with presentation at the annual meeting of the American Society of Hematology, held from Dec. 10 to 13 in San Diego.

Lili Wang, M.D., Ph.D., from the Dana-Farber Cancer Institute in Boston, and colleagues investigated the somatic genetic basis of chronic lymphocytic leukemia, using DNA samples from leukemia cells of 91 patients. The spectrum of somatic mutations was characterized using massively parallel sequencing technology of 88 whole exomes and whole genomes, along with sequencing of matched germline DNA.

The investigators identified nine genes that were mutated at significant frequencies. Four of these genes, TP53, ATM, MYD88, and NOTCH1, have established roles in chronic lymphocytic leukemia and were mutated in 15, 9, 10, and 4 percent of patients, respectively. The remaining five genes, SF3B1, ZMYM3, MAPK1, FBXW7, and DDX3X, had unestablished roles. The second most frequently mutated gene was SF3B1 (mutated in 15 percent of patients). SF3B1 mutations mainly occurred in tumors with deletions in chromosome 11q. There were alterations in pre-messenger RNA (mRNA) splicing seen in tumor samples with mutations in SF3B1.

"Our study defines the landscape of somatic mutations in chronic lymphocytic leukemia, and highlights pre-mRNA splicing as a critical cellular process contributing to chronic lymphocytic leukemia," the authors write.

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