The genomic landscape of mantle cell lymphoma is related to the epigenetically determined chromatin state of normal B cells

Jenny Zhang, Dereje Jima, Andrea B. Moffitt, Qingquan Liu, Magdalena Czader, Eric D. Hsi, Yuri Fedoriw, Cherie H. Dunphy, Kristy L. Richards, Javed I. Gill, Zhen Sun, Cassandra Love, Paula Scotland, Eric Lock, Shawn Levy, David S. Hsu, David Dunson, Sandeep S. Dave

Research output: Contribution to journalArticle

107 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2988-2996
Number of pages9
JournalBlood
Volume123
Issue number19
DOIs
StatePublished - May 8 2014

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Zhang, J., Jima, D., Moffitt, A. B., Liu, Q., Czader, M., Hsi, E. D., Fedoriw, Y., Dunphy, C. H., Richards, K. L., Gill, J. I., Sun, Z., Love, C., Scotland, P., Lock, E., Levy, S., Hsu, D. S., Dunson, D., & Dave, S. S. (2014). The genomic landscape of mantle cell lymphoma is related to the epigenetically determined chromatin state of normal B cells. Blood, 123(19), 2988-2996. https://doi.org/10.1182/blood-2013-07-517177