title: Loss of heterozygosity at 11q23 in squamous cell carcinoma of the head and neck is associated with recurrent disease.
abstract: Loss of heterozygosity (LOH) at chromosome 11q23 has been found in a variety of epithelial human neoplasms, suggesting that this region contains a tumor suppressor gene(s) important to tumorigenesis. We investigated whether LOH at 11q23 could be detected in squamous cell carcinoma of the head and neck (SCCHN), and whether loss at this site was associated with specific clinical parameters. Fifty-six matched blood and SCCHN tumor samples taken at the time of diagnosis were evaluated for LOH at three microsatellite markers at 11q23. Multiplex PCRs with [alpha-32P]dCTP labeling of the amplified DNA strands were performed. Clinical data were obtained from medical record review. LOH at 11q23 was found in 13 of 52 (25%) evaluable tumors. There was no association between LOH at 11q23 and amplification of the CCND1 (cyclin D1) oncogene or inactivation of the p53 gene, which had been determined previously. With a mean follow-up of 24 months, an association independent of tumor size or stage was found between LOH at 11q23 and recurrent disease (P = 0.04). Among subjects who received radiotherapy (RT) as a component of their treatment, LOH at 11q23 was associated with persistent or recurrent locoregional disease (P = 0.05). LOH at 11q23 occurs in a subset of SCCHN. It is associated with a higher likelihood of recurrent disease, perhaps related to resistance to RT. The specific gene(s) and mechanism(s) responsible remain to be identified. Until then, LOH at 11q23 might become a marker identifying patients likely to do poorly with conventional therapy.
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Boston University Medical Center, Massachusetts 02118-2393, USA.
authors.forename: A D
authors.initials: AD
authors.lastname: Lazar
authors.forename: M R
authors.initials: MR
authors.lastname: Winter
authors.forename: C P
authors.initials: CP
authors.lastname: Nogueira
authors.forename: P S
authors.initials: PS
authors.lastname: Larson
authors.forename: E M
authors.initials: EM
authors.lastname: Finnemore
authors.forename: R W
authors.initials: RW
authors.lastname: Dolan
authors.forename: N
authors.initials: N
authors.lastname: Fuleihan
authors.forename: A
authors.initials: A
authors.lastname: Chakravarti
authors.forename: A
authors.initials: A
authors.lastname: Zietman
authors.forename: C L
authors.initials: CL
authors.lastname: Rosenberg
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000532:radiotherapy; D002880:Chromosomes, Human, Pair 11; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000532:radiotherapy; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D017063:Outcome Assessment, Health Care; D016019:Survival Analysis