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XPC and Non-XPC Cutaneous Squamous Cell Carcinoma Mutation Rate Study

ABSTRACT:

Base mutations occur at higher frequencies within heterochromatin and late-replicating DNA. In this study, we show that regional differences in mutation frequency are absent in portions of the genome that are not transcribed within cutaneous squamous cell carcinomas (cSCCs) with an XPC-\- genetic background. The XPC-\- genetic background predicates a loss of global genome nucleotide excision repair (GG-NER), thus our data shows that regional differences in mutation frequency are a result of differential access of DNA repair protein. Unexpectedly, we also note that greater transcription reduces mutations on both strands of genes in heterochromatin, and only to those levels observed in euchromatin, in a XPC-dependent fashion. Therefore, transcription likely reduces mutation prevalence by increasing access to DNA repair proteins. This tripartite relationship between DNA repair, transcription, and chromatin state shows a new cancer risk factor in human populations.

PROVIDER: phs000830 | dbGaP |

SECONDARY ACCESSION(S): PRJNA266684PRJNA266683

REPOSITORIES: dbGaP

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			Action	DRS
	GapExchange_phs000830.v1.p1.xml	Xml
	dbGaPEx2.1.5.xsd	Other
	Study_Report.phs000830.CancerRegionalMutationRates.v1.p1.MULTI.pdf	Pdf
	manifest_phs000830.CancerRegionalMutationRates.v1.p1.c2.DS-SKCA-MDS.pdf	Pdf
	manifest_phs000830.CancerRegionalMutationRates.v1.p1.c3.DS-CA-MDS.pdf	Pdf

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