Por favor, use este identificador para citar o enlazar este ítem:
https://observatorio.fm.usp.br/handle/OPI/30118
Título: | Systematic Analysis of Splice-Site-Creating Mutations in Cancer |
Autor: | JAYASINGHE, Reyka G.; CAO, Song; GAO, Qingsong; WENDL, Michael C.; VO, Nam Sy; REYNOLDS, Sheila M.; ZHAO, Yanyan; CLIMENTE-GONZALEZ, Hector; CHAI, Shengjie; WANG, Fang; VARGHESE, Rajees; HUANG, Mo; LIANG, Wen-Wei; WYCZALKOWSKI, Matthew A.; SENGUPTA, Sohini; LI, Zhi; PAYNE, Samuel H.; FENYO, David; MINER, Jeffrey H.; WALTER, Matthew J.; VINCENT, Benjamin; EYRAS, Eduardo; CHEN, Ken; SHMULEVICH, Ilya; CHEN, Feng; DING, Li |
Citación: | CELL REPORTS, v.23, n.1, p.270-281.e3, 2018 |
Resumen: | For the past decade, cancer genomic studies have focused on mutations leading to splice-site disruption, overlooking those having splice-creating potential. Here, we applied a bioinformatic tool, MiSplice, for the large-scale discovery of splice-site-creating mutations (SCMs) across 8,656 TCGA tumors. We report 1,964 originally mis-annotated mutations having clear evidence of creating alternative splice junctions. TP53 and GATA3 have 26 and 18 SCMs, respectively, and ATRX has 5 from lower-grade gliomas. Mutations in 11 genes, including PARP1, BRCA1, and BAP1, were experimentally validated for splice-site-creating function. Notably, we found that neoantigens induced by SCMs are likely several folds more immunogenic compared to missense mutations, exemplified by the recurrent GATA3 SCM. Further, high expression of PD-1 and PD-L1 was observed in tumors with SCMs, suggesting candidates for immune blockade therapy. Our work highlights the importance of integrating DNA and RNA data for understanding the functional and the clinical implications of mutations in human diseases. |
Aparece en las colecciones: | Artigos e Materiais de Revistas Científicas - FM/Outros Artigos e Materiais de Revistas Científicas - IMT Artigos e Materiais de Revistas Científicas - LIM/14 Artigos e Materiais de Revistas Científicas - ODS/03 |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
art_JAYASINGHE_Systematic_Analysis_of_SpliceSiteCreating_Mutations_in_Cancer_2018.PDF | publishedVersion (English) | 10.34 MB | Adobe PDF | Visualizar/Abrir |
Los ítems de DSpace están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.