title: Methylation of human papillomavirus 16, 18, 31, and 45 L2 and L1 genes and the cellular DAPK gene: Considerations for use as biomarkers of the progression of cervical neoplasia.
abstract: During progression of cervical cancer, human papillomavirus genomes and cellular tumor suppressor genes can become methylated. Toward a better understanding of these biomarkers, we studied 104 samples with HPV16, 18, 31, and 45 representing five pathological categories from asymptomatic infection to cancer. We grouped all samples by HPV type and pathology and measured the overall methylation of informative amplicons of HPV late genes and the cellular DAPK gene. Methylation of all four HPV types as well as of the DAPK gene is lowest in asymptomatic infection and increases successively in all four pathological categories during progression to cancer. 27 out of 28 cancer samples showed methylation both in the L2/L1 genes as well as in DAPK, but a much lower fraction in all other pathological categories. We discuss the problem to develop diagnostic tests based on complex methylation patterns that make it difficult to classify amplicons as "methylated" or "unmethylated".
authors: Department of Dermatology, University of California Irvine, Irvine, CA 92697, United States.
authors: Mina
authors: M
authors: Kalantari
authors: Kathryn
authors: K
authors: Osann
authors: Itzel E
authors: IE
authors: Calleja-Macias
authors: Seong
authors: S
authors: Kim
authors: Bing
authors: B
authors: Yan
authors: Sara
authors: S
authors: Jordan
authors: Dana M
authors: DM
authors: Chase
authors: Krishnansu S
authors: KS
authors: Tewari
authors: Hans-Ulrich
authors: HU
authors: Bernard
mesh_terms: D052685:Alphapapillomavirus / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D064550:Death-Associated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics / Q000378:metabolism; D052161:Human papillomavirus 18 / Q000235:genetics / Q000378:metabolism; D058952:Human papillomavirus 31 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D030361:Papillomavirus Infections / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000821:virology; D011401:Promoter Regions, Genetic; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; D009856:Oncogene Proteins, Viral; C579096:DAPK1 protein, human; D064550:Death-Associated Protein Kinases
keywords: Biomarker; Cancer progression; DAPK gene; DNA methylation; Epigenetics; Papillomaviruses