TP53 GENETIC ALTERATIONS IN HEAD-AND-NECK CARCINOMAS FROM BRAZIL

In this study we investigated the incidence of mutations and loss of h eterozygosity (LOH) of the TP53 gene in DNA samples from paired tumor and adjacent normal tissue from 90 patients with untreated squamous-ce ll carcinoma of the head and neck, Evidence for TP53 mutations were de monstrated in 53% (48/90) of the cases analyzed, All cases were also e xamined for loss of heterozygosity, using a PCR-based polymorphic mark er at TP53. LOH was found in 36 out of 72 (50%) informative cases, Dir ect sequencing of PCR products was performed in 45 cases with evidence of mutations. The sequencing results revealed the presence of base-su bstitutions (67%), deletions (29%) and insertions (4%). Of the base-su bstitutions, 70% were transitions and 30% were transversions, Demograp hic variables, tumor site, stage (TNM), family history of cancer, lymp h-node involvement and histological grade were not important predictor s of TP53 mutations, Nor did TP53 genetic alterations correlate with s urvival status, In conclusion, we show that TP53 genetic alterations a re frequent in head-and-neck tumors, but are not associated with clini copathological variables or disease progression, Our study provides an evaluation of the spectrum of TP53 mutations in the pathogenesis of h ead-and-neck carcinoma in Brazil. (C) 1998 Wiley-Liss, Inc.