Oncogene and growth factor expression in MEN 2 and related tumors.

Pheochromocytomas occur sporadically or in individuals affected by inherited syndromes including multiple endocrine neoplasia (MEN) type 2A and 2B, neurofibromatosis, and the von Hippel-Lindau syndrome (vHL). Medullary thyroid carcinomas (MTCs) also occur sporadically or as part of MEN 2A, MEN 2B, and familial MTC. Little is known of the molecular genetic background of these tumors. We have shown previously that activation of the N-ras, H-ras, and K-ras oncogenes does not occur in these tumors, but that deletions of the short arm of chromosome 1 are extremely common (> 60%) and may indicate loss of a suppressor gene in the chromosomal region 1p31-36. We have examined the structure and expression of N-myc, c-myc, L-myc, c-mos, nerve growth factor (beta-NGF), and the low affinity nerve growth factor receptor (LNGFR) in a series of pheochromocytomas and MTCs from patients with hereditary and sporadic diseases. Southern analysis, using radiolabeled DNA probes, revealed no evidence of amplification or rearrangement of these genes in any normal or tumor tissues except for loss of heterozygosity at the L-myc locus (1p32) in 9 pheochromocytomas from patients with MEN 2A or MEN 2B, in 5 of 11 non-MEN pheochromocytomas, and in 3 of 24 non-MEN MTCs. Gene expression at the RNA level was examined by Northern analysis or ribonuclease protection assay (RPA) using radiolabeled DNA or cRNA probes. C-myc transcripts were detectable at low levels in all tumors tested.(ABSTRACT TRUNCATED AT 250 WORDS)