Somatic mutations of STK11 gene in human papillomavirus positive and negative penile cancer
A partir d'échantillons tumoraux de 26 patients atteints d'un carcinome épidermoïde du pénis, cette étude évalue l'association entre des mutations du gène STK11, une infection par le papillomavirus humain et le risque de cancer du pénis
BACKGROUND:Human papillomavirus (HPV) infection accounts for about 40--50% of all cases of penile carcinoma suggesting that other factors, including host genetic status, are involved in neoplastic transformation. In this perspective, STK11 gene, which has been found frequently mutated in HPV-related cervical carcinoma, has been analyzed in HPV-positive and HPV-negative invasive penile cancers to establish its mutational status and the possible correlation of HPV infection with specific genetic alterations. METHODS:Genomic DNAs extracted from 26 cases of penile squamous cell carcinoma were analyzed for genetic alterations in the exons 1 to 9 of STK11 gene by quantitative real-time PCR. Ratios of potentially deleted and non-deleted exons were indicative of specific loss of STK11 coding regions. DNA samples of 5 cancer cases were subjected to standard PCR amplification of STK11 exons 1 to 9 and analyzed for somatic mutations by direct nucleotide sequencing analysis. RESULTS:Heterozygous deletions of STK11 exon 1and 2 were identified in 2 out of 14 HPV-positive (14.3%) and 1 out of 12 HPV-negative cases (8.3%). Complete nucleotide sequencing analysis of exons 1 to 9 showed a single nucleotide change upstream the exon 2 coding region in one out of 5 penile carcinoma samples. CONCLUSIONS:The present results suggest that single nucleotide mutations and/or deletions of STK11 gene are rare events in penile cancer. Moreover, no significant association was observed between STK11 alterations and HPV infection in these tumors.