SF3B1 and Other Novel Cancer Genes in Chronic Lymphocytic Leukemia
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 paral...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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New England Journal of Medicine
2014
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| Online Access: | http://hdl.handle.net/1721.1/84659 |
| _version_ | 1826208812914180096 |
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| author | Wang, Lili Lawrence, Michael S. Wan, Youzhong Stojanov, Petar Sougnez, Carrie Stevenson, Kristen Werner, Lillian Sivachenko, Andrey DeLuca, David S. Zhang, Li Zhang, Wandi Vartanov, Alexander R. Fernandes, Stacey M. Goldstein, Natalie R. Folco, Eric G. Cibulskis, Kristian Tesar, Bethany Sievers, Quinlan L. Shefler, Erica Gabriel, Stacey B. Hacohen, Nir Reed, Robin Meyerson, Matthew L. Golub, Todd R. Neuberg, Donna S. Brown, Jennifer R. Getz, Gad Wu, Catherine J. Lander, Eric S. Lander, Eric Steven |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Wang, Lili Lawrence, Michael S. Wan, Youzhong Stojanov, Petar Sougnez, Carrie Stevenson, Kristen Werner, Lillian Sivachenko, Andrey DeLuca, David S. Zhang, Li Zhang, Wandi Vartanov, Alexander R. Fernandes, Stacey M. Goldstein, Natalie R. Folco, Eric G. Cibulskis, Kristian Tesar, Bethany Sievers, Quinlan L. Shefler, Erica Gabriel, Stacey B. Hacohen, Nir Reed, Robin Meyerson, Matthew L. Golub, Todd R. Neuberg, Donna S. Brown, Jennifer R. Getz, Gad Wu, Catherine J. Lander, Eric S. Lander, Eric Steven |
| author_sort | Wang, Lili |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T14:13:02Z |
| format | Article |
| id | mit-1721.1/84659 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:13:02Z |
| publishDate | 2014 |
| publisher | New England Journal of Medicine |
| record_format | dspace |
| spelling | mit-1721.1/846592022-10-01T19:49:33Z SF3B1 and Other Novel Cancer Genes in Chronic Lymphocytic Leukemia Wang, Lili Lawrence, Michael S. Wan, Youzhong Stojanov, Petar Sougnez, Carrie Stevenson, Kristen Werner, Lillian Sivachenko, Andrey DeLuca, David S. Zhang, Li Zhang, Wandi Vartanov, Alexander R. Fernandes, Stacey M. Goldstein, Natalie R. Folco, Eric G. Cibulskis, Kristian Tesar, Bethany Sievers, Quinlan L. Shefler, Erica Gabriel, Stacey B. Hacohen, Nir Reed, Robin Meyerson, Matthew L. Golub, Todd R. Neuberg, Donna S. Brown, Jennifer R. Getz, Gad Wu, Catherine J. Lander, Eric S. Lander, Eric Steven Massachusetts Institute of Technology. Department of Biology Lander, Eric S. 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. National Institutes of Health (U.S.). National Human Genome Research Institute (Grant U54HG003067) National Cancer Institute (U.S.) (Grant 5R21CA115043-2) 2014-02-03T20:27:29Z 2014-02-03T20:27:29Z 2011-12 Article http://purl.org/eprint/type/JournalArticle 0028-4793 1533-4406 http://hdl.handle.net/1721.1/84659 Wang, Lili, Michael S. Lawrence, Youzhong Wan, Petar Stojanov, Carrie Sougnez, Kristen Stevenson, Lillian Werner, et al. “SF3B1 and Other Novel Cancer Genes in Chronic Lymphocytic Leukemia.” New England Journal of Medicine 365, no. 26 (December 29, 2011): 2497-2506. en_US http://dx.doi.org/10.1056/NEJMoa1109016 New England Journal of Medicine Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf New England Journal of Medicine PMC |
| spellingShingle | Wang, Lili Lawrence, Michael S. Wan, Youzhong Stojanov, Petar Sougnez, Carrie Stevenson, Kristen Werner, Lillian Sivachenko, Andrey DeLuca, David S. Zhang, Li Zhang, Wandi Vartanov, Alexander R. Fernandes, Stacey M. Goldstein, Natalie R. Folco, Eric G. Cibulskis, Kristian Tesar, Bethany Sievers, Quinlan L. Shefler, Erica Gabriel, Stacey B. Hacohen, Nir Reed, Robin Meyerson, Matthew L. Golub, Todd R. Neuberg, Donna S. Brown, Jennifer R. Getz, Gad Wu, Catherine J. Lander, Eric S. Lander, Eric Steven SF3B1 and Other Novel Cancer Genes in Chronic Lymphocytic Leukemia |
| title | SF3B1 and Other Novel Cancer Genes in Chronic Lymphocytic Leukemia |
| title_full | SF3B1 and Other Novel Cancer Genes in Chronic Lymphocytic Leukemia |
| title_fullStr | SF3B1 and Other Novel Cancer Genes in Chronic Lymphocytic Leukemia |
| title_full_unstemmed | SF3B1 and Other Novel Cancer Genes in Chronic Lymphocytic Leukemia |
| title_short | SF3B1 and Other Novel Cancer Genes in Chronic Lymphocytic Leukemia |
| title_sort | sf3b1 and other novel cancer genes in chronic lymphocytic leukemia |
| url | http://hdl.handle.net/1721.1/84659 |
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