FREQUENT LOSS OF HETEROZYGOSITY FOR RB, TP53, AND CHROMOSOME ARM 3P, BUT NOT NME1 IN SQUAMOUS-CELL CARCINOMAS OF THE SUPRAGLOTTIC LARYNX

Background. The inactivation of some tumor suppresser genes classicall y manifests itself through the loss of heterozygosity at nearby geneti c mapping markers. Inactivation of these genes appears to have diagnos tic/ prognostic significance in some types of tumors. Molecular geneti c tools based on suppressor inactivation might, therefore, have great utility in treatment planning. Methods. The polymerase chain reaction and highly informative microsatellite markers were used to compare DNA derived from matched sets of tumor and normal tissue samples from 37 supraglottic laryngeal squamous cell carcinomas. Tumor samples were mi crodissected free of contaminating normal tissue to maximize the detec tion of allelic loss. Polymerase chain reaction products were fraction ated by denaturing gel electrophoresis and were visualized by autoradi ography. Results. Allelic losses were frequent at TP53 (56% of the tum ors), the retinoblastoma gene (Rb, 59%), and the p13-14 region of chro mosome 3 (64%). In contrast, the putative metastasis suppressor, NME1 (also known as NM23), was lost infrequently (7%). NME1 allelic loss di d not correlate with the presence of lymph node metastases in these pa tients. Conclusions. The high frequencies of allelic loss at TP53, Rb, and 3p13-14 suggest that these suppressors play a major role in laryn geal carcinogenesis. In sharp contrast, the low frequency of loss at N ME1 and its equal distribution in nodal metastasis-positive and -negat ive patients suggests that inactivation of this gene by allelic loss p robably does not play a role in the development of regional metastases from these tumors. Allelic loss in 3p13-14 was found in tumors of all histopathologic grades.