Loss of heterozygosity on the short arm of chromosome 1 in pheochromocytoma and abdominal paraganglioma.

Abstract

Pheochromocytomas and abdominal paragangliomas are catecholamine-producing tumors that arise from sympathetic paraganglia within and outside the adrenal medulla, respectively. Deletions of the short arm of chromosome 1 have been implicated as important genetic events in their tumorigenesis and suggest a common genetic etiology. The aim of this study was to define further the chromosomal regions on 1p that are involved in the development of these tumor types. We analyzed 46 pheochromocytomas (1 benign, 6 malignant, 9 hereditary) and 7 paragangliomas (3 benign, 4 malignant) from 50 patients for loss of heterozygosity (LOH) on 1p by genotyping 15 microsatellite markers spread over the chromosome arm. Overall, LOH was detected in 33 of 46 pheochromocytomas (72%) and in 6 of 7 (86%) paragangliomas. Three minimal regions of overlapping deletions were identified: one telomeric of D1S1612(1p36.2-pter), one centromeric of D1S429 (1cen-p13), and one in the 18 cM interval defined by D1S2134 andD1S1669 (1p32). The latter region harbors the leukocyte common antigen-related (LAR) gene, which shows altered expression in sporadic rat pheochromocytomas. In conclusion, chromosome 1p may be the site of at least three putative tumor-suppressor gene loci involved in the tumorigenesis of pheochromocytomas and abdominal paragangliomas. Further studies of these regions and of LARas a candidate gene would be valuable.