Nonsense Mutation Of XPF Gene Is Associated With Carcinogenesis

The xeroderma pigmentosum, complementation group F (XPF) gene is a keycomponent of the nucleotide excision repair (NER) mechanism, which is essential forthe protection against genetic instability and carcinogenesis. The NER mechanismrequires structure-specific excision repair cross-complimentary group1(ERCC1)/XPFinteractions.Although XPF rs2020959single nucleotide polymorphism (C2169A) wasrecorded in HEPMAP-MEX，NIHPDR，HapMap-JPT and HAPMAP-LWK populationson the basis of SNP date base, our study demonstrated that the XPF C2169A rate(C>A) was50.0%in64gastric cancer samples and the C2169A mutation was notdetected in488tumour patients’ whole blood genomic DNA samples using the TaqmanMGB probe. Further reseach indicated that the C> A nonsense mutation at position2169of the XPF gene resulted in the loss of194C-terminal amin-acids residues in XPFprotein and formed truncated XPF protein (tXPF) using overexpression XPF protein ingastric cancer cell line. The tXPF protein was charasterized by inability of interactingwith ERCC1and rapid degradation through ubiquitination and reducing DNA repaircapability. As expected, laser microdissection (LCM) confirmed that XPF C2169Amutation was present in gastric cancer tissues but not in surrounding normal tissuesfrom the same patients. Immunohistochemistry of tumor showed that XPF C2169Amutation in gastric cancer tissue accompanied with XPF low expression.The XPF C2169A mutation seems to be closely associated with gastric carcinogenesis in the Chinese population. The nonsense mutation of XPF in gastriccancer is largely monoallelic, indicating that XPF is a haplo-insufficient DNA repairgene.