Somatic Mutational Landscape of Splicing Factor Genes and Their Functional Consequences across 33 Cancer Types

M Seiler; S Peng; AA Agrawal; J Palacino; T Teng; P Zhu; PG Smith; SJ Caesar-Johnson; JA Demchok; I Felau; M Kasapi; ML Ferguson; CM Hutter; HJ Sofia; R Tarnuzzer; Z Wang; L Yang; JC Zenklusen; J Zhang; S Chudamani; J Liu; L Lolla; R Naresh; T Pihl; Q Sun; Y Wan; Y Wu; J Cho; T DeFreitas; S Frazer; N Gehlenborg; G Getz; DI Heiman; J Kim; MS Lawrence; P Lin; S Meier; MS Noble; G Saksena; D Voet; H Zhang; B Bernard; N Chambwe; V Dhankani; T Knijnenburg; R Kramer; K Leinonen; Y Liu; M Miller; S Reynolds; I Shmulevich; V Thorsson; W Zhang; R Akbani; BM Broom; AM Hegde; Z Ju; RS Kanchi; A Korkut; J Li; H Liang; S Ling; W Liu; Y Lu; GB Mills; KS Ng; A Rao; M Ryan; J Wang; JN Weinstein; J Zhang; A Abeshouse; J Armenia; D Chakravarty; WK Chatila; I de Bruijn; J Gao; BE Gross; ZJ Heins; R Kundra; K La; M Ladanyi; A Luna; MG Nissan; A Ochoa; SM Phillips; E Reznik; F Sanchez-Vega; C Sander; N Schultz; R Sheridan; SO Sumer; Y Sun; BS Taylor; J Wang; H Zhang; P Anur; M Peto; P Spellman; C Benz

Journal article

Somatic Mutational Landscape of Splicing Factor Genes and Their Functional Consequences across 33 Cancer Types

M Seiler, S Peng, AA Agrawal, J Palacino, T Teng, P Zhu, PG Smith, SJ Caesar-Johnson, JA Demchok, I Felau, M Kasapi, ML Ferguson, CM Hutter, HJ Sofia, R Tarnuzzer, Z Wang, L Yang, JC Zenklusen, J Zhang, S Chudamani Show all

Cell Reports | Published : 2018

DOI: 10.1016/j.celrep.2018.01.088

Open access

Abstract

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 wi..

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University of Melbourne Researchers

Christopher Hovens Author

Anthony Costello Author

Michael Lawrence Author

Alex Boussioutas Author

Grants

Awarded by National Institutes of Health

Funding Acknowledgements

We thank all H3 Biomedicine employees for their support in this project. We would also like to thank Collin Tokheim for his help and insight regarding the use of 20/20+. The results shown here are in whole or part based upon data generated by The Cancer Genome Atlas (TCGA) Research Network (https://cancergenome.nih.gov). The members of The Cancer Genome Atlas Research Network for this project are listed in the Supplemental Information. TCGA Research Network is supported by the following NIH grants: U54 HG003273 (Richard A. Gibbs), U54 HG003067 (Stacey Gabriel; Eric S. Lander [contact]), U54 HG003079 (Richard K. Wilson), U24 CA143799 (Terence Paul Speed; Paul T. Spellman [contact]), U24 CA143835 (Ilya Shmulevich), U24 CA143840 (Marc Ladanyi; Chris Sander [contact]), U24 CA143843 (Richard A. Gibbs; David Andrew Wheeler [contact]), U24 CA143845 (Lynda Chin [contact]; Gad Getz), U24 CA143848 (David N. Hayes; Charles M. Perou [contact]), U24 CA143858 (Joshua Stuart; Christopher Benz; David H. Haussler [contact]), U24 CA143866 (Marco Antonio Marra), U24 CA143867 (Stacey Gabriel; Matthew L. Meyerson [contact]), U24 CA143882 (Stephen B. Baylin; Peter W. Laird [contact]), U24 CA143883 (Gordon B. Mills; John N. Weinstein [contact]; W. K. Alfred Yung), U24 CA144025 (Raju S. Kucherlapati), and P30 CA016672 (Gordon B. Mills).