A comprehensive characterization of cis -acting splicing-associated variants in human cancer

Genome Research
Yuichi ShiraishiSatoru Miyano

Abstract

Although many driver mutations are thought to promote carcinogenesis via abnormal splicing, the landscape of splicing-associated variants (SAVs) remains unknown due to the complexity of splicing abnormalities. Here, we developed a statistical framework to systematically identify SAVs disrupting or newly creating splice site motifs and applied it to matched whole-exome and transcriptome sequencing data from 8976 samples across 31 cancer types, generating a catalog of 14,438 SAVs. Such a large collection of SAVs enabled us to characterize their genomic features, underlying mutational processes, and influence on cancer driver genes. In fact, ∼50% of SAVs identified were those disrupting noncanonical splice sites (non-GT-AG dinucleotides), including the third and fifth intronic bases of donor sites, or newly creating splice sites. Mutation signature analysis revealed that tobacco smoking is more strongly associated with SAVs, whereas ultraviolet exposure has less impact. SAVs showed remarkable enrichment of cancer-related genes, and as many as 14.7% of samples harbored at least one SAVs affecting them, particularly in tumor suppressors. In addition to intron retention, whose association with tumor suppressor inactivation has been p...Continue Reading

References

Apr 25, 1997·Journal of Molecular Biology·C Burge, S Karlin
Nov 25, 2003·Nucleic Acids Research·Marcel FreundHeiner Schaal
Aug 3, 2004·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Gene Yeo, Christopher B Burge
Sep 14, 2004·Oncogene·Jerry UsaryCharles M Perou
Nov 3, 2004·Cancer Research·Julian P Venables
Jan 14, 2005·Genes, Chromosomes & Cancer·Zane KalninaAija Linē
Feb 27, 2008·Proceedings of the National Academy of Sciences of the United States of America·Thomas D BarberPhilip Hieter
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
Jun 10, 2009·Bioinformatics·Heng LiUNKNOWN 1000 Genome Project Data Processing Subgroup
Apr 9, 2010·Nature Reviews. Genetics·Hadas KerenGil Ast
Jul 6, 2010·Nucleic Acids Research·Kai WangHakon Hakonarson
May 11, 2011·Nature Communications·Atsushi NishidaMasafumi Matsuo
Sep 13, 2011·Nature·Kenichi YoshidaSeishi Ogawa
Oct 30, 2012·Bioinformatics·Alexander DobinThomas R Gingeras
Dec 28, 2012·Cancer Research·Huei San LeongMarnie E Blewitt
Mar 9, 2013·Nucleic Acids Research·Yuichi ShiraishiSatoru Miyano
Mar 30, 2013·Science·Bert VogelsteinKenneth W Kinzler
Apr 2, 2013·Cell·Levi A Garraway, Eric S Lander
May 15, 2013·PLoS Genetics·Timothée FlutreMatthew Stephens
Aug 16, 2013·Nature·Ludmil B AlexandrovMichael R Stratton
Sep 24, 2013·Nature Genetics·Kenichi YoshidaSeishi Ogawa
Mar 19, 2015·Annual Review of Biochemistry·Yeon Lee, Donald C Rio
Jun 4, 2015·Annual Review of Biochemistry·Shiran NaftelbergAlberto R Kornblihtt
Sep 26, 2015·Science·Iñigo Martincorena, Peter J Campbell
Oct 6, 2015·Nature Genetics·Hyunchul JungEunjung Lee
Nov 26, 2015·Nature Reviews. Genetics·Marina M Scotti, Maurice S Swanson
Dec 3, 2015·PLoS Genetics·Yuichi ShiraishiMatthew Stephens
Jun 1, 2016·Nature Reviews. Genetics·Christopher R SibleyJernej Ule
Jun 11, 2016·Nature Reviews. Cancer·Heidi DvingeRobert K Bradley
Dec 23, 2016·Transcription·Babita Singh, Eduardo Eyras
Apr 5, 2018·Cell Reports·Reyka G JayasingheLi Ding

❮ Previous
Next ❯

Citations

Apr 18, 2019·Bioinformatics·Steven MongerEleni Giannoulatou
Oct 7, 2019·American Journal of Medical Genetics. Part a·Mamiko YamadaKenjiro Kosaki
Nov 28, 2018·Scientific Reports·Jian ZhangStephen Albert Johnston
Nov 2, 2019·Oncotarget·Esmee KoedootSylvia E Le Dévédec
May 7, 2019·Leukemia & Lymphoma·Reina TakedaArinobu Tojo
Feb 7, 2020·Nature·UNKNOWN PCAWG Transcriptome Core GroupUNKNOWN PCAWG Consortium
Feb 14, 2019·Human Genomics·Xin-Ying TangJian-Min Chen
Jul 1, 2020·Frontiers in Cell and Developmental Biology·Andrea CerasuoloMaria Lina Tornesello
Oct 15, 2019·Genomics & Informatics·Jiyeon Park, Yeun-Jun Chung
Nov 6, 2020·Nature Communications·Song CaoLi Ding
Jan 22, 2021·Seminars in Cancer Biology·Natalie Jäger
Jan 30, 2021·Clinical and Translational Gastroenterology·Shin-Ei KudoKoshi Mimori
Oct 14, 2020·Cancer Research·Geoffray MonteuuisJohn E J Rasko
Mar 18, 2021·Nature Reviews. Cancer·James R M Black, Nicholas McGranahan
Apr 7, 2021·Briefings in Bioinformatics·Yangjun ZhangHua Xu
Apr 14, 2021·Nature Biotechnology·Ira W DevesonUNKNOWN SEQC2 Oncopanel Sequencing Working Group
Jun 3, 2021·International Journal of Molecular Sciences·Maxime BlijlevensVictor W van Beusechem
Dec 11, 2021·Frontiers in Molecular Biosciences·Tülay KarakulakAbdullah Kahraman

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alternative splicing

Alternative splicing a regulated gene expression process that allows a single genetic sequence to code for multiple proteins. Here is that latest research.