Deletion mapping on the distal third region of chromosome 1p in multiple endocrine neoplasia type IIA.

Multiple endocrine neoplasia type IIA (MEN IIA) syndrome is an autosomal-dominant endocrine disorder that consists of medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid hyperplasia. The susceptibility gene to this disorder has been mapped to chromosome 10. However, molecular studies of tumor cells from patients with familial and sporadic MTC and/or pheochromocytoma have shown a high frequency (50%) of abnormalities on chromosome 1p. In the present study, we examined MTC or pheochromocytoma tumor specimens from eight patients (familial and nonfamilial cases) to investigate gene losses on chromosomes 1 and 10 as potential mechanisms for the tumors' development. The patients studies had homozygous genotypes in their leukocyte DNAs for the chromosome 10 marker used in this study, and the patients were, therefore, uninformative. However, the patients were informative for the chromosome 1 markers and five of the patients' tumor-cell DNAs (63%) had allelic deletions at one or multiple loci on chromosome 1p, and one tumor DNA had evidence of possible gene rearrangement; in all six cases, the abnormalities involved the distal third of chromosome 1p. Furthermore, we determined that the common break point for the 1p deletions was at 1p32. These results suggest that a tumor suppressor gene in this defined region is involved in the development/progression of MTC and pheochromocytoma by being either lost or inactivated.