ALLELOTYPE OF FOLLICULAR THYROID CARCINOMAS REVEALS GENETIC INSTABILITY CONSISTENT WITH FREQUENT NONDISJUNCTIONAL CHROMOSOMAL LOSS

Numerous studies aimed at the identification of chromosomal regions th at are frequently deleted in specific tumor types have pointed to the location and involvement of specific tumor suppressor genes. Previous studies of loss of heterozygosity (LOH) among thyroid tumors have reve aled frequent allelic deletions at a few chromosomal regions. A system atic genome-wide examination of LOH in a substantial number of follicu lar carcinomas, however, has not been performed previously. We assesse d LOH at polymorphic markers from each nonacrocentric autosomal arm in a panel of 28 follicular thyroid carcinoma tumor and normal pairs. In contrast to the results of previous allelotype studies, we found high rates of LOH at multiple chromosomal regions. The highest rate of los s in our study was at 2p (50.0%) and 2q (50.0%), and the mean rate of LOH was 20.4%. Marked genetic instability in a subset of tumors was de monstrated by high fractional allelic loss, which accounted for more t han 80% of observed LOH in this study. High fractional allelic loss wa s significantly associated with oxyphilic features and poor differenti ation of these tumors. Our data provide evidence of a prevalent phenot ype of nondisjunctional whole chromosomal loss in follicular thyroid c arcinomas. (C) 1997 Wiley-Liss, Inc.