Mutation analysis of the MEN1 tumour suppressor gene in malignant melanoma

During the initiation and progression of malignant melanoma a series of gen etic events accumulate, including alterations of chromosome 11q. Recently, an important tumour suppressor gene, the multiple endocrine neoplasia type 1 (MEN1) gene, has been mapped on 11q13 and has been cloned. To assess whet her the MEN1 region is involved in tumour initiation and progression, we an alysed 23 primary cutaneous melanomas and 17 metastases for loss of heteroz ygosity (LOH) using two informative polymorphic markers closely linked to t he MEN1 gene (PYGM and D11S449). To search for mutations within the gene, s ingle-strand conformation polymorphism (SSCP) analysis was performed using 13 primer sets with designed intronic sequences to amplify the MEN1 coding sequence exons 2 to 10. None of the cases showed LOH at the MEN1 gene locus . By SSCP analysis, no aberrant bands were identified on exons 3 to 10, Ana lysis of exon 2 revealed the presence of aberrant bands in two of the analy sed melanomas. Sequencing analysis revealed a genetic polymorphism at S145S (AGC-->ACT) in both sections. None of the cases analysed showed MEN1 gene mutations. This study represents the first genetic analysis of the MEN1 gen e in sporadic melanomas, our data demonstrate no evidence of deletion or mu tation of the MEN1 gene in primary or metastatic melanoma. Therefore, MEN1 gene alterations appear not to be associated with tumorigenesis of malignan t melanoma, The MEN1 gene appears to be a highly specific tumour suppressor gene only involving tumours within the spectrum of MEN1 disease. (C) 1999 Lippincott Williams & Wilkins.