TY - JOUR
T1 - The genomic landscape of mantle cell lymphoma is related to the epigenetically determined chromatin state of normal B cells
AU - Zhang, Jenny
AU - Jima, Dereje
AU - Moffitt, Andrea B.
AU - Liu, Qingquan
AU - Czader, Magdalena
AU - Hsi, Eric D.
AU - Fedoriw, Yuri
AU - Dunphy, Cherie H.
AU - Richards, Kristy L.
AU - Gill, Javed I.
AU - Sun, Zhen
AU - Love, Cassandra
AU - Scotland, Paula
AU - Lock, Eric
AU - Levy, Shawn
AU - Hsu, David S.
AU - Dunson, David
AU - Dave, Sandeep S.
PY - 2014/5/8
Y1 - 2014/5/8
N2 - In this study, we define the genetic landscape of mantle cell lymphoma (MCL) through exome sequencing of 56 cases of MCL.Weidentified recurrent mutations in ATM, CCND1, MLL2, and TP53. We further identified a number of novel genes recurrently mutated in patients with MCL including RB1, WHSC1, POT1, and SMARCA4. We noted that MCLs have a distinct mutational profile compared with lymphomas from other B-cell stages. The ENCODE project has defined the chromatin structure of many cell types. However, a similar characterization of primaryhumanmatureBcellshasbeenlacking.Wedefined, for the first time, the chromatin structureof primaryhuman na?̈ve,germinal center,andmemory B cells through chromatin immunoprecipitation and sequencing for H3K4me1, H3K4me3, H3Ac, H3K36me3, H3K27me3, and PolII.We found that somatic mutations that occur more frequently in either MCLs or Burkitt lymphomas were associated with open chromatin in their respective B cells of origin, na?̈ve B cells, and germinal center B cells. Our work thus elucidates the landscape of gene-coding mutations in MCL and the critical interplay between epigenetic alterations associated with B-cell differentiation and the acquisition of somatic mutations in cancer.
AB - In this study, we define the genetic landscape of mantle cell lymphoma (MCL) through exome sequencing of 56 cases of MCL.Weidentified recurrent mutations in ATM, CCND1, MLL2, and TP53. We further identified a number of novel genes recurrently mutated in patients with MCL including RB1, WHSC1, POT1, and SMARCA4. We noted that MCLs have a distinct mutational profile compared with lymphomas from other B-cell stages. The ENCODE project has defined the chromatin structure of many cell types. However, a similar characterization of primaryhumanmatureBcellshasbeenlacking.Wedefined, for the first time, the chromatin structureof primaryhuman na?̈ve,germinal center,andmemory B cells through chromatin immunoprecipitation and sequencing for H3K4me1, H3K4me3, H3Ac, H3K36me3, H3K27me3, and PolII.We found that somatic mutations that occur more frequently in either MCLs or Burkitt lymphomas were associated with open chromatin in their respective B cells of origin, na?̈ve B cells, and germinal center B cells. Our work thus elucidates the landscape of gene-coding mutations in MCL and the critical interplay between epigenetic alterations associated with B-cell differentiation and the acquisition of somatic mutations in cancer.
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U2 - 10.1182/blood-2013-07-517177
DO - 10.1182/blood-2013-07-517177
M3 - Article
C2 - 24682267
AN - SCOPUS:84903182870
SN - 0006-4971
VL - 123
SP - 2988
EP - 2996
JO - Blood
JF - Blood
IS - 19
ER -