Gaining insights into relevance across cancers based on mutation features of TP53 gene

The tumor suppressor gene TP53, one of the most frequently mutated genes, is recognized as the guardian of genome and can provide a significant barrier to neoplastic transformation and tumor progression. Traditional theory believes that TP53 mutations are equal among cancer types. However, to date,...

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Autores principales:	Yue Mei, Dong Liang, Tengjiao Wang, Dong Yu
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	TP53 Mutation signature Unequal Tissue-selective Digestive cancers Biology (General) QH301-705.5 Biochemistry QD415-436
Acceso en línea:	https://doaj.org/article/8f2e5ce83ab247438f93d80c852c2760
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spelling	oai:doaj.org-article:8f2e5ce83ab247438f93d80c852c27602021-11-04T04:33:11ZGaining insights into relevance across cancers based on mutation features of TP53 gene2405-580810.1016/j.bbrep.2021.101165https://doaj.org/article/8f2e5ce83ab247438f93d80c852c27602021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2405580821002594https://doaj.org/toc/2405-5808The tumor suppressor gene TP53, one of the most frequently mutated genes, is recognized as the guardian of genome and can provide a significant barrier to neoplastic transformation and tumor progression. Traditional theory believes that TP53 mutations are equal among cancer types. However, to date, no study has explored the TP53 mutation profile from a holistic and systematic standpoint to discovery its relevance and feature with cancers. Mutation signature, an unbiased approach to identify the mutational processes, can be a potent indicator for exploring mutation-driven tumor occurrence and progression. In this research, several features such as hotspots, mutability and mutation signature of somatic TP53 mutations derived from 18 types of cancer tissues from cBioPortal were analyzed and manifested the organizational preference among cancers. Mutation signatures found in almost all cancer types were Signature 6 related to mismatch repair deficiency, and Signature 1 that reflects the natural decomposition of 5-methylcytosine into thymine associated with aging. Meanwhile, several signatures of TP53 mutations displayed tissue-selective. Mutations enriched in bladder, skin, lung cancer were associated with signatures of APOBEC activity (Signature 2 and 13), alkylating agents (Signature 11), and tobacco smoke (Signature 4), respectively. Moreover, Signature 4 and 29 associated with tobacco smoking or chewing found in lung, sarcoma, esophageal, and head and neck cancer may be related to their smoking history. In addition, several digestive cancers, including colorectal, stomach, pancreatic and esophageal cancers, showed the high correlation in context and mutation signature profiles. Our study suggests that the tissue-selective activity of mutational processes would reflect the tissue-specific enrichment of TP53 mutations and provides a new perspective to understand the relevance of diverse diseases based on the spectrum of TP53 mutations.Yue MeiDong LiangTengjiao WangDong YuElsevierarticleTP53Mutation signatureUnequalTissue-selectiveDigestive cancersBiology (General)QH301-705.5BiochemistryQD415-436ENBiochemistry and Biophysics Reports, Vol 28, Iss , Pp 101165- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	TP53 Mutation signature Unequal Tissue-selective Digestive cancers Biology (General) QH301-705.5 Biochemistry QD415-436
spellingShingle	TP53 Mutation signature Unequal Tissue-selective Digestive cancers Biology (General) QH301-705.5 Biochemistry QD415-436 Yue Mei Dong Liang Tengjiao Wang Dong Yu Gaining insights into relevance across cancers based on mutation features of TP53 gene
description	The tumor suppressor gene TP53, one of the most frequently mutated genes, is recognized as the guardian of genome and can provide a significant barrier to neoplastic transformation and tumor progression. Traditional theory believes that TP53 mutations are equal among cancer types. However, to date, no study has explored the TP53 mutation profile from a holistic and systematic standpoint to discovery its relevance and feature with cancers. Mutation signature, an unbiased approach to identify the mutational processes, can be a potent indicator for exploring mutation-driven tumor occurrence and progression. In this research, several features such as hotspots, mutability and mutation signature of somatic TP53 mutations derived from 18 types of cancer tissues from cBioPortal were analyzed and manifested the organizational preference among cancers. Mutation signatures found in almost all cancer types were Signature 6 related to mismatch repair deficiency, and Signature 1 that reflects the natural decomposition of 5-methylcytosine into thymine associated with aging. Meanwhile, several signatures of TP53 mutations displayed tissue-selective. Mutations enriched in bladder, skin, lung cancer were associated with signatures of APOBEC activity (Signature 2 and 13), alkylating agents (Signature 11), and tobacco smoke (Signature 4), respectively. Moreover, Signature 4 and 29 associated with tobacco smoking or chewing found in lung, sarcoma, esophageal, and head and neck cancer may be related to their smoking history. In addition, several digestive cancers, including colorectal, stomach, pancreatic and esophageal cancers, showed the high correlation in context and mutation signature profiles. Our study suggests that the tissue-selective activity of mutational processes would reflect the tissue-specific enrichment of TP53 mutations and provides a new perspective to understand the relevance of diverse diseases based on the spectrum of TP53 mutations.
format	article
author	Yue Mei Dong Liang Tengjiao Wang Dong Yu
author_facet	Yue Mei Dong Liang Tengjiao Wang Dong Yu
author_sort	Yue Mei
title	Gaining insights into relevance across cancers based on mutation features of TP53 gene
title_short	Gaining insights into relevance across cancers based on mutation features of TP53 gene
title_full	Gaining insights into relevance across cancers based on mutation features of TP53 gene
title_fullStr	Gaining insights into relevance across cancers based on mutation features of TP53 gene
title_full_unstemmed	Gaining insights into relevance across cancers based on mutation features of TP53 gene
title_sort	gaining insights into relevance across cancers based on mutation features of tp53 gene
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/8f2e5ce83ab247438f93d80c852c2760
work_keys_str_mv	AT yuemei gaininginsightsintorelevanceacrosscancersbasedonmutationfeaturesoftp53gene AT dongliang gaininginsightsintorelevanceacrosscancersbasedonmutationfeaturesoftp53gene AT tengjiaowang gaininginsightsintorelevanceacrosscancersbasedonmutationfeaturesoftp53gene AT dongyu gaininginsightsintorelevanceacrosscancersbasedonmutationfeaturesoftp53gene
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Gaining insights into relevance across cancers based on mutation features of TP53 gene

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