¹Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9063, USA

²Department of Otolaryngology-Head and Neck Surgery, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9063, USA

³Department of Academic Computing Services, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9063, USA

^aAuthor for correspondence

Although genetic alterations of chromosome band 9p21 - 22 occur frequently in head and neck squamous cell carcinoma (HNSCC) cell lines, alterations of the cyclin-dependent kinase inhibitor p16^INK4a located in this region are less common in corresponding primary tumors. To further investigate genetic alterations at 9p21 - 22 and p16^INK4a in primary HNSCC, a paired set of 21 tumors and blood specimens that were shown previously to exhibit allelic loss at 3p and elsewhere, were tested for LOH at 9p21 - 22 using eight different highly polymorphic marker. Sixteen of the samples (81%) exhibited LOH for at least one marker. Frequent LOH was found surrounding p16^INK4a and at three additional non-contiguous regions of 9p21 - 22. No homozygous deletions were identified. SSCP screening and direct sequence analysis led to the identification of mutations the p16^INK4a gene in two tumors. p16^INK4a was not hypermethylated in any of the samples studied. Furthermore, there was no correlation between LOH at 9p21 - 22 and the RB1 tumor suppressor gene. These findings indicate that in the set of tumors that we tested, LOH at 9p21 - 22 is common in primary HNSCC but that genetic alterations of p16^INK4a located in this region are unusual. Additional tumor suppressor genes at 9p21 - 22 may therefore be involved in the pathogenesis of this tumor.

p16^INK4a; cyclin-dependent kinase inhibitors; chromosome 9; loss of heterozygosity; squamous cell carcinoma of the head and neck