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. DESIGN 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. SUBJECTS 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.

[1]  F. Prósper,et al.  Promoter hypermethylation of cancer-related genes: a strong independent prognostic factor in acute lymphoblastic leukemia. , 2004, Blood.

[2]  E. İskender,et al.  Hypermethylation of tumor suppressor genes (p16INK4A, p14ARF and APC) in adenocarcinomas of the upper gastrointestinal tract , 2004, International journal of cancer.

[3]  Hyeon Joo Lee,et al.  Aberrant CpG island hypermethylation of multiple genes in colorectal neoplasia , 2004, Laboratory Investigation.

[4]  Y. Shim,et al.  Tumor-specific methylation in bronchial lavage for the early detection of non-small-cell lung cancer. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  R. Uzzo,et al.  Promoter Hypermethylation Profile of Kidney Cancer , 2004, Clinical Cancer Research.

[6]  R. Weber,et al.  Differential Methylation Status of Tumor-Associated Genes in Head and Neck Squamous Carcinoma , 2004, Clinical Cancer Research.

[7]  P. Cairns.  Detection of Promoter Hypermethylation of Tumor Suppressor Genes in Urine from Kidney Cancer Patients , 2004, Annals of the New York Academy of Sciences.

[8]  Shou‐Tung Chen,et al.  Promoter CpG methylation of caveolin-1 in sporadic colorectal cancer. , 2004, Anticancer research.

[9]  J. Rey,et al.  Aberrant CpG Island Methylation of Multiple Genes in Ependymal Tumors , 2004, Journal of Neuro-Oncology.

[10]  J. Rey,et al.  Methylation status of TP73 in meningiomas. , 2004, Cancer genetics and cytogenetics.

[11]  A. Hui,et al.  Epigenetic inactivation of TSLC1 gene in nasopharyngeal carcinoma , 2003, Molecular carcinogenesis.

[12]  M. Imamura,et al.  Involvement of TSLC1 in progression of esophageal squamous cell carcinoma. , 2003, Cancer research.

[13]  Tsung-Teh Wu,et al.  Prognostic importance of promoter hypermethylation of multiple genes in esophageal adenocarcinoma. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[14]  J. Schouten,et al.  Delineating genetic pathways of disease progression in head and neck squamous cell carcinoma. , 2003, Archives of otolaryngology--head & neck surgery.

[15]  N. Tsuchida,et al.  Promoter hypermethylation profile of tumor‐associated genes p16, p15, hMLH1, MGMT and E‐cadherin in oral squamous cell carcinoma , 2003, International journal of cancer.

[16]  D. Kwong,et al.  Differential gene methylation in undifferentiated nasopharyngeal carcinoma. , 2003, International journal of oncology.

[17]  C. Plass,et al.  Differential targets of CpG island hypermethylation in primary and metastatic head and neck squamous cell carcinoma (HNSCC) , 2003, Journal of medical genetics.

[18]  K. Kelsey,et al.  Patterns of gene promoter methylation in squamous cell cancer of the head and neck , 2002, Oncogene.

[19]  D. Zwijnenburg,et al.  Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification. , 2002, Nucleic acids research.

[20]  Peter A. Jones,et al.  The fundamental role of epigenetic events in cancer , 2002, Nature Reviews Genetics.

[21]  R. Lotan,et al.  Differential effects of chromosome 3p deletion on the expression of the putative tumor suppressor RARβ and on retinoid resistance in human squamous carcinoma cells , 2001, Oncogene.

[22]  K. Jung,et al.  Expression of the normal epithelial cell-specific 1 (NES1; KLK10) candidate tumour suppressor gene in normal and malignant testicular tissue , 2001, British Journal of Cancer.

[23]  C. Plass,et al.  Methylation matters , 2001, Journal of medical genetics.

[24]  J. Herman,et al.  A gene hypermethylation profile of human cancer. , 2001, Cancer research.

[25]  H. Fukuhara,et al.  TSLC1 is a tumor-suppressor gene in human non-small-cell lung cancer , 2001, Nature Genetics.

[26]  J. Jen,et al.  Promoter hypermethylation patterns of p16, O6-methylguanine-DNA-methyltransferase, and death-associated protein kinase in tumors and saliva of head and neck cancer patients. , 2001, Cancer research.

[27]  P. Laird,et al.  Fields of aberrant CpG island hypermethylation in Barrett's esophagus and associated adenocarcinoma. , 2000, Cancer research.

[28]  J. Herman,et al.  DNA hypermethylation in tumorigenesis: epigenetics joins genetics. , 2000, Trends in genetics : TIG.

[29]  J. Herman,et al.  Gene promoter hypermethylation in tumors and serum of head and neck cancer patients. , 2000, Cancer research.

[30]  M. Caligiuri,et al.  Aberrant CpG-island methylation has non-random and tumour-type–specific patterns , 2000, Nature Genetics.

[31]  M. Nagai,et al.  High prevalence of p16 genetic alterations in head and neck tumours , 1999, British Journal of Cancer.

[32]  Peter A. Jones,et al.  Cancer-epigenetics comes of age , 1999, Nature Genetics.

[33]  S. Hirohashi.  Inactivation of the E-cadherin-mediated cell adhesion system in human cancers. , 1998, The American journal of pathology.

[34]  P Hunt,et al.  Localization of tumor suppressor activity important in nonsmall cell lung carcinoma on chromosome 11q. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[35]  S. Nomoto,et al.  Search for mutations and examination of allelic expression imbalance of the p73 gene at 1p36.33 in human lung cancers. , 1998, Cancer research.

[36]  A. El‐Naggar,et al.  Methylation, a major mechanism of p16/CDKN2 gene inactivation in head and neck squamous carcinoma. , 1997, The American journal of pathology.

[37]  A. Yang,et al.  Monoallelically Expressed Gene Related to p53 at 1p36, a Region Frequently Deleted in Neuroblastoma and Other Human Cancers , 1997, Cell.

[38]  R. Lotan,et al.  Differential expression of nuclear retinoid receptors in normal, premalignant, and malignant head and neck tissues. , 1994, Cancer research.

[39]  Rudolf Jaenisch,et al.  Role for DNA methylation in genomic imprinting , 1993, Nature.

[40]  S. Baylin,et al.  Increased cytosine DNA-methyltransferase activity during colon cancer progression. , 1993, Journal of the National Cancer Institute.

[41]  Rudolf Jaenisch,et al.  Targeted mutation of the DNA methyltransferase gene results in embryonic lethality , 1992, Cell.

[42]  T. Carey,et al.  11p Deletions and breakpoints in squamous cell carcinoma: Association with altered reactivity with the UM‐E7 antibody , 1991, Genes, chromosomes & cancer.

[43]  A. Pegg,et al.  Mammalian O6-alkylguanine-DNA alkyltransferase: regulation and importance in response to alkylating carcinogenic and therapeutic agents. , 1990, Cancer research.

[44]  Robert L. Tanguay,et al.  In vivo footprint and methylation analysis by PCR-aided genomic sequencing: comparison of active and inactive X chromosomal DNA at the CpG island and promoter of human PGK-1. , 1990, Genes & development.

[45]  D. Schwartz,et al.  Characterization of human laryngeal primary and metastatic squamous cell carcinoma cell lines UM-SCC-17A and UM-SCC-17B. , 1989, Cancer research.

[46]  E. Tahara.  Genetic pathways of two types of gastric cancer. , 2004, IARC scientific publications.

[47]  A. Jemal,et al.  Cancer Statistics, 2004 , 2004, CA: a cancer journal for clinicians.

[48]  P. Johnson,et al.  Promoter hypermethylation of multiple genes in nasopharyngeal carcinoma. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[49]  G. Liang,et al.  Relationship between transcription and DNA methylation. , 2000, Current topics in microbiology and immunology.

[50]  J. Herman,et al.  Alterations in DNA methylation: a fundamental aspect of neoplasia. , 1998, Advances in cancer research.

[51]  C. Wittekind.  [Prognostic factors in liver tumors]. , 1995, Verhandlungen der Deutschen Gesellschaft fur Pathologie.

[52]  N. Dubrawsky.  Cancer statistics , 1989, CA: a cancer journal for clinicians.