Somatic Mutation Analysis of the MEN1 Gene in Adrenocortical Tumors using Denaturing Gradient Gel Electrophoresis (DGGE)

Adrenocortical tumors are rare neoplasms, encountered either sporadically or as a familial cluster, notably in the context of multiple endocrine neoplasia type 1 (MEN1). Allelic loss of IIqI3 markers has been described in a few adrenal tumors, implicating the involvement of the MEN1 gene in the pathogenesis of these tumors. To assess the extent of the involvement of the MEN1 gene in adrenocortical tumorigenesis, we analyzed 26 sporadically occurring adrenocortical tumors for somatic mutations in the MEN I gene. PCR amplification of all MEN1 gene coding exons was followed by denaturing gradient gel electrophoresis (DGGE) analysis, and complemented by DNA sequencing of abnormally migrating fragments. Six of 26 tumors displayed distinct, novel sequence altERαtions: two frameshift and two missense mutations in exon 10, one missense mutation in exon 6, and an intronic altERαtion at -41 from the splice site at intron 9, of unknown significance. We conclude that the MEN1 gene is involved in adrenocortical tumor development. KEY WORDS adrenal tumors, DGGE, somatic mutations, MEN1.