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Seiler, Michael; Smith, Peter G.; Liu, Yuexin; Reynolds, Sheila; Phillips, Sarah M.; Spellman, Paul; Holt, Robert; Schein, Jacqueline E.; Sipahimalani, Payal; Thiessen, Nina; Van Den Berg, David J.; Weisenberger, Daniel J.; Bodenheimer, Tom; Mieczkowski, Piotr A.; Veluvolu, Umadevi; Zhou, Wanding; Bellair, Michelle; Gibbs, Richard A.; Li, Wei; Zhao, Fengmei; Ding, Li; Mardis, Elaine R.; Mallery, David; Paulauskis, Joseph; Corcoran, Niall; Carvalho, Andre L.; Vidal, Daniel O.; Ittmann, Michael; Lyadov, Vladimir; Shabunin, Alexey; Barrett, Wendi; De Rose, Agostino; Giuliante, Felice; Hagedorn, Curt H.; Hu, Hai; Bennett, Joseph; Hibshoosh, Hanina; Potapova, Olga; Voronina, Olga; Berchuck, Andrew; McCall, Shannon; Secord, Angeles; Olson, Jeffrey J.; Ramalingam, Suresh; Stoop, Hans; Cuppini, Lucia; Hanh, Phan Thi; Akeredolu, Teniola; Kang, Koo Jeong; Birrer, Michael; Castle, Erik; Kopp, Karla; Roberts, Lewis; Yang, Ju Dong; Angulo Gonzalez, Ana Maria; Bondaruk, Jolanta; Broaddus, Russell; Fujimoto, Junya; Guo, Charles; Ramondetta, Lois; Tsao, Anne; Wistuba, Ignacio; Haydu, Lauren; Scolyer, Richard; Thompson, John; Reuter, Victor; Drwiega, Paul; Metwalli, Adam R.; Pinto, Peter A.; Vocke, Cathy D.; Botnariuc, Natalia; Gorincioi, Ghenadie; Alexopoulou, Iakovina; Tamakawa, Raina; Chevalier, Simone; Schilero, Cathy; Smolenski, Kathy; Borgia, Jeffrey A.; Junker, Kerstin; Aziz, Dina; Hilty, Joe; Lehman, Norman L.; Tischler, Arthur; Henderson, Joel; Schadendorf, Dirk; Nelson, Mark; Carney, Michael; Hernandez, Brenda; Knutson, Tina; Godwin, Andrew K.; Saad, Fred; Valdivieso, Federico; Sankarankuty, Ajith; Catto, James; Creaney, Jenette; Prince, Mark; Fong, Kwun M.; Kovatich, Albert J.; Aredes, Natália D.; Yu, Lihua
Cell reports (Cambridge), 04/2018, Letnik: 23, Številka: 1Journal Article
Hotspot mutations in splicing factor genes have been recently reported at high frequency in hematological malignancies, suggesting the importance of RNA splicing in cancer. We analyzed whole-exome sequencing data across 33 tumor types in The Cancer Genome Atlas (TCGA), and we identified 119 splicing factor genes with significant non-silent mutation patterns, including mutation over-representation, recurrent loss of function (tumor suppressor-like), or hotspot mutation profile (oncogene-like). Furthermore, RNA sequencing analysis revealed altered splicing events associated with selected splicing factor mutations. In addition, we were able to identify common gene pathway profiles associated with the presence of these mutations. Our analysis suggests that somatic alteration of genes involved in the RNA-splicing process is common in cancer and may represent an underappreciated hallmark of tumorigenesis. Display omitted •119 splicing factor genes carry putative driver mutations in one or more cancer types•BLCA and UVM carry more driver splicing factor mutations than expected by chance•Common splicing factor mutations associated with lineage-independent altered splicing•Mutations are associated with deregulation of cell-autonomous pathways and immune infiltration Seiler et al. report that 119 splicing factor genes carry putative driver mutations over 33 tumor types in TCGA. The most common mutations appear to be mutually exclusive and are associated with lineage-independent altered splicing. Samples with these mutations show deregulation of cell-autonomous pathways and immune infiltration.
