DELETION MAPPING OF ENDOCRINE TUMORS LOCALIZES A 2ND TUMOR-SUPPRESSORGENE ON CHROMOSOME BAND 11Q13

Multiple endocrine neoplasia type I syndrome (MEN1, MIM 131100), an au tosomal dominant disease, is characterized by parathyroid hyperplasia, pancreatic endocrine tumors, and pituitary adenomas, These tumors als o occur sporadically. Both the familial (MEN I) and the sporadic tumor s reveal loss of heterozygosity (LOH) for chromosome band 11q13 sequen ces. Based on prior linkage and LOH analyses, the MEN1 gene was locali zed between PYGM and D11S460. Recently, the MEN1 gene(menin) has been cloned from sequences 30-kb distal to PYGM. We performed-deletion mapp ing on 25 endocrine tumors (5 MEN1 and 20 sporadic) by using 21 polymo rphic markers on chromosome band 11q13. Of these, two (137C7A, 137C7B) were derived from PYGM-containing BAC (bacterial artificial chromosom e-137C7) sequences, one from INT2-containing cosmid sequences and the marker D11S4748, a (CA)(20) repeat marker that was developed by us. Th e LOH analysis shows that the markers close to the MEN1 (menin) gene w ere not deleted in three of the tumors. These tumors, however, showed LOH for distal markers. Thus, the data suggest the existence of a seco nd tumor suppressor gene on chromosome band 11q13. (C) 1998 Wiley-Liss , Inc.