Deletion and mutation of WWOX exons 6–8 in human non-small cell lung cancer

Abstract

To examine the deletion and point mutation of WWOX (WW domain containing oxidoreductase) exons 6–8 in human non-small cell lung cancer and their possible relationship with pathological stages, tumor tissues and the corresponding normal tissues were obtained from 44 Chinese patients who had undergone surgery for non-small cell lung cancer. RNA was extracted from each sample and deletion and mutation of WWOX exons 6–8 were analyzed by RT-PCR and DNA sequencing. Our results showed that 28 of 44 (63.6%) lung cancer samples showed loss of WWOX exons 6–8 transcript and the deletion was detected in only 3 of 44 (6.8%) corresponding adjacent normal tissues (P<0.05). The transcript sequencing analyses of the 16 lung cancer samples without transcript loss of WWOX exons 6–8 revealed no difference from the sequence of Gen-Bank. Moreover, the deletion of WWOX exons 6–8 was significantly higher in the smokers when compared with the non-smokers. It is also higher in the men and squamous carcinomas than in women and adenocarcinomas (P<0.05). The deletion, however, was not found to be associated with pathological stages of the tumors. Our study documented a high incidence of deletion of WWOX exons 6–8 in non-small cell lung cancer in Chinese patients and suggested that the frequent loss of WWOX exons 6–8 might play an important role in the tumorigenesis of non-small cell lung cancer in Chinese. WWOX exons 6–8 may serves as a candidate molecular target of smoking carcinogenesis, and point mutation is not a predominant way of alteration of WWOX exons 6–8.

Keywords

non-small cell lung cancer / WWOX gene / exon / point mutation / RT-PCR / cDNA-sequencing

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