MEN1 gene analysis in sporadic adrenocortical neoplasms

Adrenocortical tumors occur as sporadic tumors, as part of the multiple end ocrine neoplasia type 1 (MEN1) syndrome or as part of other hereditary diso rders. We recently cloned the MEN1 gene, a tumor-suppressor gene located on chromosome 11q13. Subsequently, we showed that sequential somatic inactiva tion of both alleles of the MEN1 gene contributes to the development of som e sporadic endocrine neoplasms (parathyroid, enteropancreatic neuroendocrin e, branchial carcinoid, and pituitary tumors). We now studied whether somat ic inactivation of the MEN1 gene contributes to the pathogenesis of sporadi c adrenocortical neoplasms. Seven adrenocortical carcinomas, 2 adrenocortic al carcinoma cell Lines, and 11 aldosterone-secreting, 8 cortisol-secreting , and 5 nonsecreting benign adrenocortical tumors were studied. Seven tumor s (5 of 5 carcinomas, 2 of 21 nonsecreting benign adenomas; P < 0.001) exhi bited loss of heterozygosity on 11q13. All 33 tumors and cell lines were sc reened for mutation throughout the MEN1 open-reading frame and adjacent spl ice junctions. None exhibited a mutation within the MEN1-coding region. We conclude that somatic MEN1 mutation within the MEN1-coding region does not occur commonly in sporadic adrenocortical tumors, although the majority of adrenocortical carcinomas exhibit 11q13 loss of heterozygosity.