Genotyping of adrenocortical tumors: Very frequent deletions of the MEN1 locus in 11q13 and of a 1-centimorgan region in 2p16

To identify chromosomal regions that may contain loci for tumor suppressor genes involved in adrenocortical tumor development, a panel of 60 tumors (3 9 carcinomas and 21 adenomas) were screened for loss of heterozygosity. Alt hough the vast majority of loss of heterozygosity (LOH) were detected in th e carcinomas and involved chromosomes 2, 4, 11, and 18, only few were found in the adenomas. Therefore, 2 loci that harbor the familial cancer syndrom es Carney complex in 2p16 and the multiple endocrine neoplasia type 1 gene in 11q13 were further studied in 27 (13 carcinomas and 14 adenomas) of the 60 tumors. Detailed analysis of the 2p16 region mapped a minimal area of ov erlapping deletions to a l-centimorgan region, which is separate from the C arney complex locus. LOH for a micro-satellite marker (PYGM), very close to the MEN1 gene, was detected the 27 cases analyzed in detail, 13 cases (11 carcinomas and 2 adenomas) showed LOH on chromosome 11 and was therefore se lected for MEN1 gene mutation analysis. In 6 cases a common polymorphism (A sp(418)Asp) was found, but no mutation was detected. In conclusion, our dat a indicate the existence of tumor suppressor genes at multiple chromosomal locations, whose inactivations are involved in the development of adrenocor tical carcinomas. Loss of genetic material from 2p16 was strongly associate d with the malignant phenotype, as it was seen in almost all carcinomas but not in any of the adenomas. LOH in 11q13 also occurred frequently in the c arcinomas, but was not associated with a MEN1 mutation, suggesting the invo lvement of a different tumor suppressor gene on this chromosome.