The genomic landscape of mantle cell lymphoma is related to the epigenetically determined chromatin state of normal B cells.
In this study, we define the genetic landscape of mantle cell lymphoma (MCL) through exome sequencing of 56 cases of MCL. We identified 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 primary human mature B cells has been lacking. We defined, for the first time, the chromatin structure of primary human naïve, germinal center, and memory 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, naïve 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.
Duke Scholars
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- Tumor Suppressor Protein p53
- Transcription Factors
- Telomere-Binding Proteins
- Shelterin Complex
- Sequence Analysis, DNA
- Retinoblastoma Protein
- Repressor Proteins
- Nuclear Proteins
- Neoplasm Proteins
- Mutation
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Tumor Suppressor Protein p53
- Transcription Factors
- Telomere-Binding Proteins
- Shelterin Complex
- Sequence Analysis, DNA
- Retinoblastoma Protein
- Repressor Proteins
- Nuclear Proteins
- Neoplasm Proteins
- Mutation