Malignant melanoma in patients with multiple endocrine neoplasia type 1 and involvement of the MEN1 gene in sporadic melanoma

Multiple endocrine neoplasia type 1 (MEN 1) is a familial cancer syndrome a ssociated primarily with endocrine tumors of the parathyroids, enteropancre as and anterior pituitary. However, tumors of mesenchymal origin such as an giofibroma and collagenoma of the skin have also been associated with the s yndrome. This highlights the possibility of an association between MEN 1 an d some other types of tumors. Here we report 7 cases of primary malignant m elanoma occurring in 7 MEN 1 families, all patients exhibiting classic feat ures of MEN 1. Based on these findings and the previous implication of mult iple melanoma tumor suppressor(s) in 11q, including the MEN1 region, we hav e investigated the involvement of the MEN1 gene in melanoma tumorigenesis. Mutation analysis was performed on a panel of 39 sporadic metastatic melano mas, 13 melanoma cell lines and 20 melanoma families without CDKN2A or CDK4 germline mutations. In addition, 19 sporadic metastatic tumors were screen ed for loss of heterozygosity (LOH) in 11q13. LOH was detected in 6 tumors (32%), and in 4 of the tumors the pattern of LOH suggested that the deletio n included the MEN1 gene locus. A novel somatic nonsense mutation in exon 7 (Q349X) was identified in 1 sporadic tumor which also showed loss of the w ild-type allele. We conclude that the MEN1 gene plays a role in the tumorig enesis of a small subgroup of melanoma. Int. J. Cancer 87:463-467, 2000. (C ) 2000 Wiley-Liss, Inc.