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Open Access Research article

Somatic mutations of STK11 gene in human papillomavirus positive and negative penile cancer

Clorinda Annunziata1, Luigi Buonaguro1, Simona Losito2, Franco M Buonaguro1 and Maria Lina Tornesello1*

Author Affiliations

1 Molecular Biology and Viral Oncology, National Cancer Institute "Fond. Pascale", Cappella Cangiani, 80131, Naples, Italy

2 Department of Pathology, National Cancer Institute "Fond. Pascale", Naples, Italy

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Infectious Agents and Cancer 2013, 8:2  doi:10.1186/1750-9378-8-2

Published: 10 January 2013

Abstract

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 1 and 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 1 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.

Keywords:
HPV; STK11; Somatic mutations; Penile cancer