Human papillomavirus DNA and oncogene alterations in colorectal tumors

Pathol Oncol Res. 2010 Sep;16(3):461-8. doi: 10.1007/s12253-010-9246-x. Epub 2010 Mar 17.

Abstract

The aim of the present study is to determine the presence and molecular integrity of high-risk HPV types in colorectal adenocarcinomas and to assess whether viral DNA is related to common proto-oncogene alterations, such as k-ras mutations and c-myc gene amplification, in colorectal cancer. Seventy-five colorectal adenocarcinomas were screened for HPV infection using nested-PCR (MY09/11-GP5+/6+). HPV typing was performed by type-specific PCR for HPV 16 and HPV 18 DNA. Unidentified samples were subsequently sequenced to determine the viral genotype. The physical status of HPV was determined by a nested PCR approach for type-specific E2 sequences. C-myc amplification was assessed by co-amplification with β-globin as control locus, and mutation in k-ras codons 12 and 13 by ARMS-PCR. Overall, HPV was detected in thirty-three colorectal specimens (44%). HPV 16 was the prevalent type (16/75), followed by HPV 18 (15/75), HPV 31 (1/75) and HPV 66 (1/75). E2 disruption was detected in 56.3% of HPV 16 and in 40% of HPV 18 positive tumors. C-myc amplification was detected in 29.4% of cases, while k-ras mutations in 30.7%. There was no significant trend for HPV infection in tumors harboring either k-ras or c-myc alterations. This study demonstrates HPV DNA and viral integration in colorectal tumors, suggesting a potential role of this virus in colorectal carcinogenesis. There was no concurrence, however, of k-ras and c-myc activation with viral infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / virology*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / virology*
  • DNA, Viral / analysis
  • DNA, Viral / genetics
  • Female
  • Gene Amplification
  • Genes, myc
  • Genes, ras
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Oncogenes
  • Papillomaviridae / genetics
  • Papillomavirus Infections / genetics*
  • Polymerase Chain Reaction
  • Virus Integration / genetics

Substances

  • DNA, Viral