Evolution and Impact of Subclonal Mutations in Chronic Lymphocytic Leukemia
Clonal evolution is a key feature of cancer progression and relapse. We studied intratumoral heterogeneity in 149 chronic lymphocytic leukemia (CLL) cases by integrating whole-exome sequence and copy number to measure the fraction of cancer cells harboring each somatic mutation. We identified driver...
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| Format: | Article |
| Language: | en_US |
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Elsevier
2014
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| Online Access: | http://hdl.handle.net/1721.1/85572 |
| _version_ | 1826192321974108160 |
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| author | Landau, Dan A. Carter, Scott L. Stojanov, Petar McKenna, Aaron Stevenson, Kristen Lawrence, Michael S. Sougnez, Carrie Stewart, Chip Sivachenko, Andrey Wang, Lili Wan, Youzhong Zhang, Wandi Shukla, Sachet A. Vartanov, Alexander Fernandes, Stacey M. Saksena, Gordon Cibulskis, Kristian Tesar, Bethany Gabriel, Stacey B. Hacohen, Nir Meyerson, Matthew L. Neuberg, Donna S. Brown, Jennifer R. Getz, Gad Wu, Catherine J. Lander, Eric Steven |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Landau, Dan A. Carter, Scott L. Stojanov, Petar McKenna, Aaron Stevenson, Kristen Lawrence, Michael S. Sougnez, Carrie Stewart, Chip Sivachenko, Andrey Wang, Lili Wan, Youzhong Zhang, Wandi Shukla, Sachet A. Vartanov, Alexander Fernandes, Stacey M. Saksena, Gordon Cibulskis, Kristian Tesar, Bethany Gabriel, Stacey B. Hacohen, Nir Meyerson, Matthew L. Neuberg, Donna S. Brown, Jennifer R. Getz, Gad Wu, Catherine J. Lander, Eric Steven |
| author_sort | Landau, Dan A. |
| collection | MIT |
| description | Clonal evolution is a key feature of cancer progression and relapse. We studied intratumoral heterogeneity in 149 chronic lymphocytic leukemia (CLL) cases by integrating whole-exome sequence and copy number to measure the fraction of cancer cells harboring each somatic mutation. We identified driver mutations as predominantly clonal (e.g., MYD88, trisomy 12, and del(13q)) or subclonal (e.g., SF3B1 and TP53), corresponding to earlier and later events in CLL evolution. We sampled leukemia cells from 18 patients at two time points. Ten of twelve CLL cases treated with chemotherapy (but only one of six without treatment) underwent clonal evolution, predominantly involving subclones with driver mutations (e.g., SF3B1 and TP53) that expanded over time. Furthermore, presence of a subclonal driver mutation was an independent risk factor for rapid disease progression. Our study thus uncovers patterns of clonal evolution in CLL, providing insights into its stepwise transformation, and links the presence of subclones with adverse clinical outcomes. |
| first_indexed | 2024-09-23T09:09:23Z |
| format | Article |
| id | mit-1721.1/85572 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:09:23Z |
| publishDate | 2014 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/855722022-09-30T13:50:58Z Evolution and Impact of Subclonal Mutations in Chronic Lymphocytic Leukemia Landau, Dan A. Carter, Scott L. Stojanov, Petar McKenna, Aaron Stevenson, Kristen Lawrence, Michael S. Sougnez, Carrie Stewart, Chip Sivachenko, Andrey Wang, Lili Wan, Youzhong Zhang, Wandi Shukla, Sachet A. Vartanov, Alexander Fernandes, Stacey M. Saksena, Gordon Cibulskis, Kristian Tesar, Bethany Gabriel, Stacey B. Hacohen, Nir Meyerson, Matthew L. Neuberg, Donna S. Brown, Jennifer R. Getz, Gad Wu, Catherine J. Lander, Eric Steven Massachusetts Institute of Technology. Department of Biology Lander, Eric S. Clonal evolution is a key feature of cancer progression and relapse. We studied intratumoral heterogeneity in 149 chronic lymphocytic leukemia (CLL) cases by integrating whole-exome sequence and copy number to measure the fraction of cancer cells harboring each somatic mutation. We identified driver mutations as predominantly clonal (e.g., MYD88, trisomy 12, and del(13q)) or subclonal (e.g., SF3B1 and TP53), corresponding to earlier and later events in CLL evolution. We sampled leukemia cells from 18 patients at two time points. Ten of twelve CLL cases treated with chemotherapy (but only one of six without treatment) underwent clonal evolution, predominantly involving subclones with driver mutations (e.g., SF3B1 and TP53) that expanded over time. Furthermore, presence of a subclonal driver mutation was an independent risk factor for rapid disease progression. Our study thus uncovers patterns of clonal evolution in CLL, providing insights into its stepwise transformation, and links the presence of subclones with adverse clinical outcomes. National Institute of General Medical Sciences (U.S.) (NHGRI-U54HG003067) 2014-03-10T16:15:55Z 2014-03-10T16:15:55Z 2013-02 Article http://purl.org/eprint/type/JournalArticle 00928674 1097-4172 http://hdl.handle.net/1721.1/85572 Landau, Dan A., Scott L. Carter, Petar Stojanov, Aaron McKenna, Kristen Stevenson, Michael S. Lawrence, Carrie Sougnez, et al. “Evolution and Impact of Subclonal Mutations in Chronic Lymphocytic Leukemia.” Cell 152, no. 4 (February 2013): 714–726. Copyright © 2013 Elsevier Inc. en_US http://dx.doi.org/10.1016/j.cell.2013.01.019 Cell Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier Elsevier Open Archive |
| spellingShingle | Landau, Dan A. Carter, Scott L. Stojanov, Petar McKenna, Aaron Stevenson, Kristen Lawrence, Michael S. Sougnez, Carrie Stewart, Chip Sivachenko, Andrey Wang, Lili Wan, Youzhong Zhang, Wandi Shukla, Sachet A. Vartanov, Alexander Fernandes, Stacey M. Saksena, Gordon Cibulskis, Kristian Tesar, Bethany Gabriel, Stacey B. Hacohen, Nir Meyerson, Matthew L. Neuberg, Donna S. Brown, Jennifer R. Getz, Gad Wu, Catherine J. Lander, Eric Steven Evolution and Impact of Subclonal Mutations in Chronic Lymphocytic Leukemia |
| title | Evolution and Impact of Subclonal Mutations in Chronic Lymphocytic Leukemia |
| title_full | Evolution and Impact of Subclonal Mutations in Chronic Lymphocytic Leukemia |
| title_fullStr | Evolution and Impact of Subclonal Mutations in Chronic Lymphocytic Leukemia |
| title_full_unstemmed | Evolution and Impact of Subclonal Mutations in Chronic Lymphocytic Leukemia |
| title_short | Evolution and Impact of Subclonal Mutations in Chronic Lymphocytic Leukemia |
| title_sort | evolution and impact of subclonal mutations in chronic lymphocytic leukemia |
| url | http://hdl.handle.net/1721.1/85572 |
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