Genomic Integration of High-Risk HPV Alters Gene Expression in Oropharyngeal Squamous Cell Carcinoma

In this study, viral factors were examined for possible clues to differences in tumor behavior. Oropharynx tumors that responded well to therapy were compared with those that persisted and recurred. Viral oncogene alternate transcripts were assessed, and cellular sites of viral integration were mapped and sequenced. Effects of integration on gene expression were assessed by transcript analysis at the integration sites. All of the tumors demonstrated active viral oncogenesis, indicated by expression of HPV E6 and E7 oncogenes and alternate E6 splicing. In the responsive tumors, HPV integration occurred exclusively in intergenic chromosome regions, except for one tumor with viral integration into TP63. Each recurrent tumor exhibited complex HPV integration patterns into cancer-associated genes, including TNFRSF13B, SCN2A, SH2B1, UBE2V2, SMOC1, NFIA, and SEMA6D. Disrupted cellular transcripts were identified in the region of integration in four of the seven affected genes.
Implications: Integration of transcriptionally active hrHPV into cellular intergenic regions associates with tumor behavior by altering gene expression. Mol Cancer Res; 14(10); 941–52. ©2016 AACR.

Source: Molecular Cancer Research - October 12, 2016 Category: Cancer & Oncology Authors: Walline, H. M., Komarck, C. M., McHugh, J. B., Bellile, E. L., Brenner, J. C., Prince, M. E., McKean, E. L., Chepeha, D. B., Wolf, G. T., Worden, F. P., Bradford, C. R., Carey, T. E. Tags: Genomics Source Type: research