Abstract 3172: Detection of viral HPV DNA in sporadic colorectal cancers in relation to CpG island methylator phenotype (CIMP)

Background: There is evidence that insertion of viral DNA into a mammalian genome can lead to alterations of methylation patterns. To test the possible correlation between epigenetic modulations in colorectal cancer (CRC) and HPV infection, we conducted a MSP- PCR methylation analysis. The aim of the present study was to examine the presence of DNA sequences of human papillomavirus (HPV) in CRC and correlate this data with their CIMP status. Methods: Thirty-seven colorectal adenocarcinomas were screened for HPV infection using nested-PCR (PGMY09/11-GP5+/6+). HPV typing was performed by type-specific PCR for HPV 16 and HPV 18 DNA. Eight CpG island methylator phenotype (CIMP) genes specific to sporadic colorectal cancer (MLH1, CACNA1G, NEUROG1, IGF2, SOCS1, RUNX3, CDKN2A and CRABP1) were assessed by methylation-specific PCR. Results: Thirty-seven CRC cases (mean age at diagnosis 63.2 ± 11.7 years; 17 males) were evaluated. Tumors were mostly located in the left colon (73.0%), and moderate differentiated (61.1%). HPV's DNA was identified in 23 of 37 (62.2%) CRC studied cases. CRABP1 (59.5%), CDKN2A (37.8%), MLH1 (13.5%), and NEUROG1 (10.8%) were the most commonly methylated genes with a discrete clinic-pathological phenotype and gene methylation pattern. No statistical associations between HPV status and methylation patterns were found, after correlation with tumor staging, cell differentiation, tumor location, and life style. Discussion: We reported that the CIMP-hypermethylation may be less frequent among Puerto Ricans Hispanics than previously reported in other racial and/or ethnic groups. However, a correlation could not be established (p>0.5) between HPV infection and the aberrant methylation pattern in the genes panel. We observed the trend that HPV is more prevalent in CRC without aberrant methylation patterns. This might suggest that hypermethylation could be a protective factor for HPV infection. This inference may mean that HPV positive colorectal cancer could represent a distinctive clinical and epidemiological condition compared with HPV-negative CRC. Citation Format: Raul D. Bernabe-Dones, Wesley Villavicencio-Torres, Cristina Munoz-Masso, Yaritza Reyes -Medina, Lorena Marcano-Bonilla, Hector Perez-Cantalapiedra, Sharon Fonseca-Williams, Mercedes Y. Lacourt-Ventura, Yasuhiro Yamamura, Nayra Rodriguez, Marcia R. Cruz-Correa. Detection of viral HPV DNA in sporadic colorectal cancers in relation to CpG island methylator phenotype (CIMP). [abstract].