ORIGINAL ARTICLE

Differential targets of CpG island hypermethylation in primary and metastatic head and neck squamous cell carcinoma (HNSCC)

D J Smiraglia¹, L T Smith¹, J C Lang², L J Rush^1,3, Z Dai^1,4, D E Schuller², C Plass¹

¹ Division of Human Cancer Genetics, Department of Molecular Virology, Immunology and Medical Genetics, and Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA
² Department of Otolaryngology, and Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA
³ Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio 43210, USA
⁴ Department of Pathology, and Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA

Correspondence to:
Correspondence to:
Dr D J Smiraglia, The Ohio State University, Department of Molecular Virology, Immunology and Medical Genetics, Division of Human Cancer Genetics, 420 West 12th Avenue, Medical Research Facility, Room 470A, Columbus, OH 43210, USA;
Smiraglia.1{at}osu.edu

Head and neck squamous cell carcinomas (HNSCC) often metastasise to the cervical lymph nodes. It is known for HNSCC as well as other cancers that progression from normal tissue to primary tumour and finally to metastatic tumour is characterised by an accumulation of genetic mutations. DNA methylation, an epigenetic modification, can result in loss of gene function in cancer, similar to genetic mutations such as deletions and point mutations. We have investigated the DNA methylation phenotypes of both primary HNSCC and metastatic tumours from 13 patients using restriction landmark genomic scanning (RLGS). With this technique, we were able to assess the methylation status of an average of nearly 1300 CpG islands for each tumour. We observed that the number of CpG islands hypermethylated in metastatic tumours is significantly greater than what is found in the primary tumours overall, but not in every patient. Interestingly, the data also clearly show that many loci methylated in a patient’s primary tumour are no longer methylated in the metastatic tumour of the same patient. Thus, even though metastatic HNSCC methylate a greater proportion of CpG islands than do the primary tumours, they do so at different subsets of loci. These data show an unanticipated variability in the methylation state of loci in primary and metastatic HNSCCs within the same patient. We discuss two possible explanations for how different epigenetic events might arise between the primary tumour and the metastatic tumour of a person.

Keywords: DNA methylation; CpG island; HNSCC; primary tumour; metastatic tumour

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