THE HUMAN HNP36 GENE IS LOCALIZED TO CHROMOSOME 11Q13 AND PRODUCES ALTERNATIVE TRANSCRIPTS THAT ARE NOT MUTATED IN MULTIPLE ENDOCRINE NEOPLASIA, TYPE-1 (MEN-I) SYNDROME

Multiple endocrine neoplasia, type 1 (MEN I), is an autosomal dominant syndrome of selected endocrine neoplasms whose causative gene, a susp ected tumor suppressor, has been localized to chromosome 11q13, but ha s not been identified. Recently, the HNP36 cDNA was identified as a no vel growth factor responsive gene of undetermined biological function that is expressed in the pituitary and parathyroid glands. In studies seeking the function of the HNP36 gene product, the gene was localized by fluorescence in situ hybridization within the 11q13 segment. Furth er analysis of radiation-reduced hybrid DNAs and chromosome 11-specifi c YAC clones established that the HNP36 gene is within 80 kb of D11S91 3, a marker tightly linked to the MEN1 gene. Consequently, the HNP36 g ene was studied as a candidate for the MEN1 gene. The human HNP36 gene was cloned and determined to consist of 12 exons. Expression of the H NP36 gene from pituitary and parathyroid tissue and four patient tumor s or lymphoblasts was confirmed by RT-PCR amplification of the coding sequences, and HNP36 transcripts were analyzed for mutations. All tiss ues expressed three HNP36 gene transcripts that result from alternativ e splicing and appear to encode related, but distinct, proteins, Howev er, DNA sequence determination of the RT-PCR products from MEN I-assoc iated tumors found no deletions and identified a single nucleotide dif ference that may be a polymorphism. Thus, mutations in the coding segm ents of the HNP36 gene are not the cause of the MEN I syndrome. Nevert heless, the assignment of the HNP36 gene to 11q13 and identification o f new potential gene products provides a novel growth-regulated geneti c candidate for other disorders whose genes map to this locus. (C) 199 7 Academic Press.