Reduced XPC DNA repair gene mRNA levels in clinically normal parents of xeroderma pigmentosum patients

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dc.authoridKraemer, Kenneth/0000-0002-2689-3316
dc.authoridKHAN, SIKANDAR/0000-0001-9957-4132
dc.authoridDiGiovanna, John J./0000-0002-2750-2313
dc.authorwosidMetin, Ahmet/ABB-7187-2020
dc.authorwosidMetin, Ahmet/HJY-7499-2023
dc.contributor.authorKhan, SG
dc.contributor.authorOh, KS
dc.contributor.authorShahlavi, T
dc.contributor.authorUeda, T
dc.contributor.authorBusch, DB
dc.contributor.authorInui, H
dc.contributor.authorEmmert, S
dc.date.accessioned2024-08-04T20:15:11Z
dc.date.available2024-08-04T20:15:11Z
dc.date.issued2006
dc.departmentİnönü Üniversitesien_US
dc.description.abstractXeroderma pigmentosum group C (XP-C) is a rare autosomal recessive disorder. Patients with two mutant alleles of the XPC DNA repair gene have sun sensitivity and a 1000-fold increase in skin cancers. Clinically normal parents of XP-C patients have one mutant allele and one normal allele. As a step toward evaluating cancer risk in these XPC heterozygotes we characterized cells from 16 XP families. We identified 15 causative mutations (5 frameshift, 6 nonsense and 4 splicing) in the XPC gene in cells from 16 XP probands. All had premature termination codons (PTC) and absence of normal XPC protein on western blotting. The cell lines from 26 parents were heterozygous for the same mutations. We employed a real-time quantitative reverse transcriptase-PCR assay as a rapid and sensitive method to measure XPC mRNA levels. The mean XPC mRNA levels in the cell lines from the XP-C probands were 24% (P < 10(-7)) of that in 10 normal controls. This reduced XPC mRNA level in cells from XP-C patients was caused by the PTC that induces nonsense-mediated mRNA decay. The mean XPC mRNA levels in cell lines from the heterozygous XP-C carriers were intermediate (59%, P = 10(-4)) between the values for the XP patients and the normal controls. This study demonstrates reduced XPC mRNA levels in XP-C patients and heterozygotes. Thus, XPC mRNA levels may be evaluated as a marker of cancer susceptibility in carriers of mutations in the XPC gene.en_US
dc.description.sponsorshipIntramural NIH HHS [Z01 BC004517-31] Funding Source: Medlineen_US
dc.identifier.doi10.1093/carcin/bgi204
dc.identifier.endpage94en_US
dc.identifier.issn0143-3334
dc.identifier.issn1460-2180
dc.identifier.issue1en_US
dc.identifier.pmid16081512en_US
dc.identifier.scopus2-s2.0-29744457502en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage84en_US
dc.identifier.urihttps://doi.org/10.1093/carcin/bgi204
dc.identifier.urihttps://hdl.handle.net/11616/94207
dc.identifier.volume27en_US
dc.identifier.wosWOS:000234219300008en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherOxford Univ Pressen_US
dc.relation.ispartofCarcinogenesisen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectNucleotide Excision-Repairen_US
dc.subjectC Protein Complexen_US
dc.subjectMutant Miceen_US
dc.subjectInformation-Contenten_US
dc.subjectMolecular Analysisen_US
dc.subjectCockayne-Syndromeen_US
dc.subjectSkin-Canceren_US
dc.subjectMutationsen_US
dc.subjectGenotypeen_US
dc.subjectDecayen_US
dc.titleReduced XPC DNA repair gene mRNA levels in clinically normal parents of xeroderma pigmentosum patientsen_US
dc.typeArticleen_US

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