SF3B1 and Other Novel Cancer Genes in Chronic Lymphocytic Leukemia

By Lili Wang, M. Lawrence, Youzhong Wan, P. Stojanov, C. Sougnez, K. Stevenson, L. Werner, A. Sivachenko, D. DeLuca, Li Zhang and 19 more. New England Journal of Medicine, 2011

1,266 citations recorded by the source corpus.

Background The somatic genetic basis of chronic lymphocytic leukemia, a common and clinically heterogeneous leukemia occurring in adults, remains poorly understood. Methods We obtained DNA samples from leukemia cells in 91 patients with chronic lymphocytic leukemia and performed massively parallel sequencing of 88 whole exomes and whole genomes, together with sequencing of matched germline DNA, to characterize the spectrum of somatic mutations in this disease. Results Nine genes that are mutated at significant frequencies were identified, including four with established roles in chronic lymphocytic leukemia (TP53 in 15% of patients, ATM in 9%, MYD88 in 10%, and NOTCH1 in 4%) and five with unestablished roles (SF3B1, ZMYM3, MAPK1, FBXW7, and DDX3X). SF3B1, which functions at the catalytic core of the spliceosome, was the second most frequently mutated gene (with mutations occurring in 15% of patients). SF3B1 mutations occurred primarily in tumors with deletions in chromosome 11q, which are associated with a poor prognosis in patients with chronic lymphocytic leukemia. We further discovered that tumor samples with mutations in SF3B1 had alterations in pre–messenger RNA (mRNA) splicing. Conclusions 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.

Subfields: Genetics, Molecular Biology, Pathology and Forensic Medicine

View Paper: https://www.semanticscholar.org/paper/74b2b0f6cd14263baca7f04c05d460a633265a1d

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Citations in the corpus

Three-year follow-up of treatment-naïve and previously treated patients with CLL and SLL receiving single-agent ibrutinib. (2015, neutral): “Median prior therapy, n (range) — 4 (1-12)”
Comprehensive molecular portraits of human breast tumors (2012, neutral): “Mutation of splicing factor SF3B1 , previously described in myelodysplastic syndromes 21 and chronic lymphocytic leukaemia 22 , was significant with 15 non-silent mutations, of which 4 were a recurrent K700E substitution.”
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