Genomic landscape of human papillomavirus-associated cancers
#MMPMID25779941
Rusan M
; Li YY
; Hammerman PS
Clin Cancer Res
2015[May]; 21
(9
): 2009-19
PMID25779941
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Recent next-generation sequencing studies have generated a comprehensive overview
of the genomic landscape of human papillomavirus (HPV)-associated cancers. This
review summarizes these findings to provide insight into the tumor biology of
these cancers and potential therapeutic opportunities for HPV-driven
malignancies. In addition to the tumorigenic properties of the HPV oncoproteins,
integration of HPV DNA into the host genome is suggested to be a driver of the
neoplastic process. Integration may confer a growth and survival advantage via
enhanced expression of viral oncoproteins, alteration of critical cellular genes,
and changes in global promoter methylation and transcription. Alteration of
cellular genes may lead to loss of function of tumor suppressor genes, enhanced
oncogene expression, loss of function of DNA repair genes, or other vital
cellular functions. Recurrent integrations in RAD51B, NR4A2, and TP63, leading to
aberrant forms of these proteins, are observed in both HPV-positive head and neck
squamous cell carcinoma (HNSCC) and cervical carcinoma. Additional genomic
alterations, independent of integration events, include recurrent PIK3CA
mutations (and aberrations in other members of the PI3K pathway), alterations in
receptor tyrosine kinases (primarily FGFR2 and FGFR3 in HPV-positive HNSCC, and
ERBB2 in cervical squamous cell carcinoma), and genes in pathways related to
squamous cell differentiation and immune responses. A number of the alterations
identified are potentially targetable, which may lead to advances in the
treatment of HPV-associated cancers.
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