Dissemin is shutting down on January 1st, 2025

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American Society of Hematology, Blood, 16(124), p. 2544-2553, 2014

DOI: 10.1182/blood-2013-12-546309

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Exome sequencing reveals novel mutation targets in diffuse large B-cell lymphomas derived from Chinese patients

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Preprint: archiving forbidden
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Postprint: archiving restricted
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Data provided by SHERPA/RoMEO

Abstract

Next generation sequencing studies on diffuse large B cell lymphomas (DLBCL) have revealed novel targets of genetic aberrations but also high inter-cohort heterogeneity. Previous studies have suggested that the prevalence of disease sub-groups and cytogenetic profiles differ between Western and Asian patients. In order to characterize the coding genome of Chinese DLBCL, we performed whole-exome sequencing of DNA derived from 31 tumors and respective peripheral blood samples. The mutation prevalence of B2M, CD70, DTX1, LYN, TMSB4X, and UBE2A were investigated in additional 105 tumor samples. We discovered 11 novel targets of recurrent mutations in DLBCL that included functionally relevant genes such as LYN and TMSB4X. Additional genes were found mutated at high frequency (≥10%) in the Chinese cohort including DTX1, which was the most prevalent mutation target in the Notch pathway. We furthermore demonstrated that mutations in DTX1 impair its function as a negative regulator of Notch. Novel and previous unappreciated targets of somatic mutations in DLBCL identified in this study support the existence of additional/alternative tumorigenic pathways in these tumors. The observed differences with previous reports might be explained by the genetic heterogeneity of DLBCL, the germline genetic makeup of Chinese individuals and/or exposure to distinct etiological agents.