TY - JOUR
T1 - Somatic Mutational Landscape of Splicing Factor Genes and Their Functional Consequences across 33 Cancer Types
AU - The Cancer Genome Atlas Research Network
AU - Seiler, Michael
AU - Peng, Shouyong
AU - Agrawal, Anant A.
AU - Palacino, James
AU - Teng, Teng
AU - Zhu, Ping
AU - Liu, Yuexin
AU - Zhang, Wei
AU - Akbani, Rehan
AU - Broom, Bradley M.
AU - Ju, Zhenlin
AU - Kanchi, Rupa Sridevi
AU - Korkut, Anil
AU - Li, Jun
AU - Liang, Han
AU - Ling, Shiyun
AU - Liu, Wenbin
AU - Lu, Yiling
AU - Mills, Gordon B
AU - Uppore Kukkillaya, Arvind Rao
AU - Weinstein, John N.
AU - Zhang, Jiexin
AU - Liu, Xiuping
AU - Wang, Linghua
AU - Carvalho, André L.
AU - Fregnani, José Humberto T. G.
AU - Reis, Rui M. V.
AU - Scapulatempo, Cristovam Neto
AU - Ajani, Jaffer A.
AU - Behrens, Carmen
AU - Bondaruk, Jolanta
AU - Broaddus, Russell
AU - Czerniak, Bogdan
AU - Esmaeli, Bita
AU - Fujimoto, Junya
AU - Gershenwald, Jeffrey
AU - Guo, Charles
AU - Lazar, Alexander J.
AU - Logothetis, Christopher
AU - Meric-Bernstam, Funda
AU - Moran, Cesar
AU - Ramondetta, Lois
AU - Rice, David
AU - Sood, Anil
AU - Tamboli, Pheroze
AU - Thompson, Timothy
AU - Troncoso, Patricia
AU - Tsao, Anne
AU - Wistuba, Ignacio
AU - von Deimling, Andreas
N1 - Publisher Copyright:
© 2018 The Authors
PY - 2018/4/3
Y1 - 2018/4/3
N2 - 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. 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.
AB - 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. 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.
KW - FUBP1
KW - RBM10
KW - SF3B1
KW - SRSF2
KW - U2AF1
KW - cancer
KW - mutation
KW - splicing
UR - http://www.scopus.com/inward/record.url?scp=85044920109&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85044920109&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2018.01.088
DO - 10.1016/j.celrep.2018.01.088
M3 - Article
C2 - 29617667
AN - SCOPUS:85044920109
SN - 2211-1247
VL - 23
SP - 282-296.e4
JO - Cell Reports
JF - Cell Reports
IS - 1
ER -