Epigenetic events of disease progression in head and neck squamous cell carcinoma.
OBJECTIVE
To examine the promoter methylation status of the 22 cancer genes and their contribution to disease progression in 6 head and neck squamous cell carcinoma (HNSCC) cell lines.


METHODS
A panel of 41 gene probes, designed to interrogate 35 unique genes with known associations to cancer including HNSCC, was interrogated for alterations in gene copy number and aberrant methylation status (22 genes) using the methylation-specific multiplex ligation-dependent probe amplification assay.


METHODS
Primary (A) and recurrent or metastatic (B) HNSCC cell lines UMSCC-11A/11B, UMSCC-17A/17B, and UMSCC-81A/81B are described.


RESULTS
Nine genes, TIMP3, APC, KLK10, TP73, CDH13, IGSF4, FHIT, ESR1, and DAPK1, were aberrantly methylated. The most frequently hypermethylated genes were APC and IGSF4, observed in 3 of 6 cell lines, and TP73 and DAPK1, observed in 2 of 6. For KLK10 and IGSF4, TIMP3 and FHIT, and TP73, in UMSCC-11B, UMSCC-17B, and UMSCC-81B, respectively, promoter hypermethylation was a disease progression event, indicating complete abrogation of tumor suppressor function for KLK10, IGSF4, and TIMP3 and gene silencing of 1 of 2 copies of TP73. Hypermethylation of IGSF4, TP73, CDH13, ESR1, DAPK1, and APC were primary events in UMSCC-17A.


CONCLUSIONS
Gene silencing through promoter hypermethylation was observed in 5 of 6 cell lines and contributed to primary and progressive events in HNSCC. In addition to genetic alterations of gains and losses, epigenetic events appear to further undermine a destabilized genomic repertoire in HNSCC.
Worsham
Maria J
MJ
Department of Otolaryngology-Head and Neck Surgery and Research Division, Henry Ford Health System, Detroit, Mich, USA. mworsha1@hfhs.org
Chen
Kang Mei
KM
Meduri
Venkata
V
Nygren
Anders O H
AO
Errami
Abdellatif
A
Schouten
Jan P
JP
Benninger
Michael S
MS
D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D002460:Cell Line; D019175:DNA Methylation; D018450:Disease Progression; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D014407:Tumor Cells, Cultured