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

• Tipo: Artigo em Revista Científica Internacional
• Data: 2014

Autores

de Miranda, NFCC (Autor) Outra; Georgiou, K (Autor) Outra; Chen, LY (Autor) Outra; Wu, CL (Autor) Outra; Gao, ZB (Autor) Outra; Zaravinos, A (Autor) Outra; Lisboa, S (Autor) Outra; Enblad, G (Autor) Outra; Manuel R Teixeira (Autor) ICBAS; Zeng, YX (Autor) Outra; Peng, RJ (Autor) Outra; Pan Hammarstrom, Q (Autor) Outra

Revista

Título: Blood

Vol. 124

Páginas: 2544-2553

ISSN: 0006-4971

Editora: Elsevier

Indexação

ISI Web of Knowledge - 79 Citações

Scopus - 80 Citações

Outras Informações

ID Authenticus: P-009-WGF

DOI: 10.1182/blood-2013-12-546309

Abstract (EN): Next-generation sequencing studies on diffuse large B-cell lymphomas (DLBCLs) have revealed novel targets of genetic aberrations but also high intercohort heterogeneity. Previous studies have suggested that the prevalence of disease subgroups and cytogenetic profiles differ between Western and Asian patients. 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 was investigated in an 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 10