期刊
PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE
卷 32, 期 5-6, 页码 276-283出版社
WILEY
DOI: 10.1111/phpp.12251
关键词
skin cancer; sun sensitivity; xeroderma pigmentosum; XP complementation group C; XPC
类别
资金
- Heinz und Heide Durr Stiftung
- Niedersachsische Krebsgesellschaft e.V.
- Claudia von Schilling Breast Cancer Foundation
- Deutsche Krebshilfe e.V.
- RSCF [14-15-00396]
- Russian Science Foundation [14-15-00396] Funding Source: Russian Science Foundation
BackgroundThe nucleotide excision repair (NER) pathway, defective in xeroderma pigmentosum (XP) patients, removes DNA photolesions in order to prevent carcinogenesis. Complementation group C (XP-C) is the most frequent group of XP patients worldwide. MethodsWe analyzed seven XP-C patients clinically and molecular-genetically applying: post-UV cell survival (MTT-assay), quantitative Real-time PCR, sequencing on chromosomal as well as cDNA level, and in silico interpretation of sequencing data. ResultsAll cases displayed diminished post-UV cell survival as well as reduced XPCmRNA levels. Five homozygous and two heterozygous disease causing mutations were identified. A large chromosomal deletion of similar to 5.8 kb identified in XP174MA leads to an unique in frame deletion of XPC exon 2 and exon 3. In silico analysis revealed the deletion of 102 amino acids in the N-terminal part of XPC while leaving the C-terminal domain intact. The novel c.361delA mutation in XP168MA leads to a frameshift in exon 3 resulting in a premature stop codon 27 codons downstream of the deleted adenine. ConclusionOur analysis confirms that XP-C patients without increased sun sensitivity develop non-melanoma skin cancers earlier than sun-sensitive XP-C patients. Reduced cellular mRNA levels are characteristic for XP complementation group C and qRT-PCR represents a rapid diagnostic tool.
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