Human papillomavirus DNA and oncogene alterations in colorectal tumors.
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.
Institute of Veterinary Genetics-National Council of Scientific and Technical Investigations, National University of La Plata, 60 and 118 street, La Plata, Buenos Aires, Argentina. perezlo@gmail.com
Luis Orlando
LO
Pérez
Gisela
G
Barbisan
Anabel
A
Ottino
Horacio
H
Pianzola
Carlos Daniel
CD
Golijow
D000230:Adenocarcinoma / Q000235:genetics* / Q000821:virology*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D016259:Genes, myc; D011905:Genes, ras; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009857:Oncogenes; D027383:Papillomaviridae / Q000235:genetics; D030361:Papillomavirus Infections / Q000235:genetics*; D016133:Polymerase Chain Reaction; D000090063:Proto-Oncogene Mas; D016662:Virus Integration / Q000235:genetics
D004279:DNA, Viral; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas