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.

Somatic Mutational Landscape of Splicing Factor Genes and Their Functional Consequences across 33 Cancer Types / Michael, Seiler; Shouyong, Peng; Anant A, Agrawal; James, Palacino; Teng, Teng; Ping, Zhu; Peter G, Smith; Alvaro, Domenico; Bragazzi, MARIA CONSIGLIA; Cardinale, Vincenzo; Gaudio, Eugenio; Silvia, Buonamici; Lihua, Yu. - In: CELL REPORTS. - ISSN 2211-1247. - 23:1(2018), pp. 282-296.e4-296.e4. [10.1016/j.celrep.2018.01.088]

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

Domenico, Alvaro;Maria C. , Bragazzi;Vincenzo, Cardinale;Eugenio, Gaudio;
2018

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 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.
2018
FUBP1; RBM10; SF3B1; SRSF2; U2AF1; cancer; mutation; splicing
01 Pubblicazione su rivista::01a Articolo in rivista
Somatic Mutational Landscape of Splicing Factor Genes and Their Functional Consequences across 33 Cancer Types / Michael, Seiler; Shouyong, Peng; Anant A, Agrawal; James, Palacino; Teng, Teng; Ping, Zhu; Peter G, Smith; Alvaro, Domenico; Bragazzi, MARIA CONSIGLIA; Cardinale, Vincenzo; Gaudio, Eugenio; Silvia, Buonamici; Lihua, Yu. - In: CELL REPORTS. - ISSN 2211-1247. - 23:1(2018), pp. 282-296.e4-296.e4. [10.1016/j.celrep.2018.01.088]
File allegati a questo prodotto
File Dimensione Formato  
Seiler_somatic-mutational_2018.pdf

accesso aperto

Tipologia: Documento in Post-print (versione successiva alla peer review e accettata per la pubblicazione)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 1.42 MB
Formato Adobe PDF
1.42 MB Adobe PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1106360
Citazioni
  • ???jsp.display-item.citation.pmc??? 137
  • Scopus 256
  • ???jsp.display-item.citation.isi??? 255
social impact