Allelic imbalance of somatic mutations in cancer genomes and transcriptomes

Abstract Somatic mutations in cancer genomes often show allelic imbalance (AI) of mutation abundance between the genome and transcriptome, but there is not yet a systematic understanding of AI. In this study, we performed large-scale DNA and RNA AI analyses of >100,000 somatic mutations in >2,...

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Autores principales:	Je-Keun Rhee, Sejoon Lee, Woong-Yang Park, Young-Ho Kim, Tae-Min Kim
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d31a65fa049e4af980dc48a053f953c3
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spelling	oai:doaj.org-article:d31a65fa049e4af980dc48a053f953c32021-12-02T16:06:40ZAllelic imbalance of somatic mutations in cancer genomes and transcriptomes10.1038/s41598-017-01966-z2045-2322https://doaj.org/article/d31a65fa049e4af980dc48a053f953c32017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01966-zhttps://doaj.org/toc/2045-2322Abstract Somatic mutations in cancer genomes often show allelic imbalance (AI) of mutation abundance between the genome and transcriptome, but there is not yet a systematic understanding of AI. In this study, we performed large-scale DNA and RNA AI analyses of >100,000 somatic mutations in >2,000 cancer specimens across five tumor types using the exome and transcriptome sequencing data of the Cancer Genome Atlas consortium. First, AI analysis of nonsense mutations and frameshift indels revealed that nonsense-mediated decay is typical in cancer genomes, and we identified the relationship between the extent of AI and the location of mutations in addition to the well-recognized 50-nt rules. Second, the AI with splice site mutations may reflect the extent of intron retention and is frequently observed in known tumor suppressor genes. For missense mutations, we observed that mutations frequently subject to AI are enriched to genes related to cancer, especially those of apoptosis and the extracellular matrix, and C:G > A:T transversions. Our results suggest that mutations in known cancer-related genes and their transcripts are subjected to different levels of transcriptional or posttranscriptional regulation compared to wildtype alleles and may add an additional regulatory layer to the functions of cancer-relevant genes.Je-Keun RheeSejoon LeeWoong-Yang ParkYoung-Ho KimTae-Min KimNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Je-Keun Rhee Sejoon Lee Woong-Yang Park Young-Ho Kim Tae-Min Kim Allelic imbalance of somatic mutations in cancer genomes and transcriptomes
description	Abstract Somatic mutations in cancer genomes often show allelic imbalance (AI) of mutation abundance between the genome and transcriptome, but there is not yet a systematic understanding of AI. In this study, we performed large-scale DNA and RNA AI analyses of >100,000 somatic mutations in >2,000 cancer specimens across five tumor types using the exome and transcriptome sequencing data of the Cancer Genome Atlas consortium. First, AI analysis of nonsense mutations and frameshift indels revealed that nonsense-mediated decay is typical in cancer genomes, and we identified the relationship between the extent of AI and the location of mutations in addition to the well-recognized 50-nt rules. Second, the AI with splice site mutations may reflect the extent of intron retention and is frequently observed in known tumor suppressor genes. For missense mutations, we observed that mutations frequently subject to AI are enriched to genes related to cancer, especially those of apoptosis and the extracellular matrix, and C:G > A:T transversions. Our results suggest that mutations in known cancer-related genes and their transcripts are subjected to different levels of transcriptional or posttranscriptional regulation compared to wildtype alleles and may add an additional regulatory layer to the functions of cancer-relevant genes.
format	article
author	Je-Keun Rhee Sejoon Lee Woong-Yang Park Young-Ho Kim Tae-Min Kim
author_facet	Je-Keun Rhee Sejoon Lee Woong-Yang Park Young-Ho Kim Tae-Min Kim
author_sort	Je-Keun Rhee
title	Allelic imbalance of somatic mutations in cancer genomes and transcriptomes
title_short	Allelic imbalance of somatic mutations in cancer genomes and transcriptomes
title_full	Allelic imbalance of somatic mutations in cancer genomes and transcriptomes
title_fullStr	Allelic imbalance of somatic mutations in cancer genomes and transcriptomes
title_full_unstemmed	Allelic imbalance of somatic mutations in cancer genomes and transcriptomes
title_sort	allelic imbalance of somatic mutations in cancer genomes and transcriptomes
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/d31a65fa049e4af980dc48a053f953c3
work_keys_str_mv	AT jekeunrhee allelicimbalanceofsomaticmutationsincancergenomesandtranscriptomes AT sejoonlee allelicimbalanceofsomaticmutationsincancergenomesandtranscriptomes AT woongyangpark allelicimbalanceofsomaticmutationsincancergenomesandtranscriptomes AT younghokim allelicimbalanceofsomaticmutationsincancergenomesandtranscriptomes AT taeminkim allelicimbalanceofsomaticmutationsincancergenomesandtranscriptomes
_version_	1718384933166120960

Allelic imbalance of somatic mutations in cancer genomes and transcriptomes

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