ALLELIC LOSS AND REPLICATION ERRORS AT MICROSATELLITE LOCI ON CHROMOSOME 11P IN HEAD AND NECK SQUAMOUS CARCINOMA - ASSOCIATION WITH AGGRESSIVE BIOLOGICAL FEATURES

The frequent loss of heterozygosity (LOH) demonstrated at chromosome 1 1p regions in several sporadic malignancies has suggested the presence of tumor suppressor genes at these locations, To obtain detailed mapp ed incidence of the microsatellite alterations at these regions and to investigate the possible correlation between the genotype and the pat hobiological characteristics of head and neck squamous carcinoma, we a nalyzed paired DNA samples from normal mucosa and primary tumor specim ens from 56 patients with these tumors, Our results show that 50.9% of the tumors had microsatellite alterations at one or more of these loc i, LOH was manifested in 45.5% and instability in 5.5% of the tumors, 11p15 loci showed more frequent LOH (39.6%) than those of 11p13 (29.3% ) and 11p11-12 (18.8%); the D11S988 (11p15) marker showed the highest single locus incidence of LOH (29.7%), Eight tumors (22.2%) demonstrat ed simultaneous LOH at both the 11p15 and 11p13 regions, LOH was signi ficantly associated with poor histological differentiation, DNA aneupl oids, and high proliferative activity in these neoplasms, Our study ex tends the involvement of the 11p13 and 11p15 regions to head and neck squamous tumorigenesis and indicates that the terminal loci of 11p may harbor a tumor suppressor gene(s) associated with the progression of these tumors.