Alternative genetic pathways in parathyroid tumorigenesis

In this study 44 parathyroid tumors from 26 sporadic cases, 10 cases previo usly given irradiation to the neck, and 8 familial cases were screened for sequence copy number alterations by comparative genomic hybridization. In t he sporadic adenomas, commonly occurring minimal regions of loss could be d efined to chromosome 11 (38%), 15q15-qter (27%), and 1p34-pter (19%), where as gains preferentially involved 19p13.2-pter (15%) and 7pter-qter (12%). M ultiple aberrations were found in sporadic tumors with a somatic mutation a nd/or loss of heterozygosity of the MEN1 gene. The irradiation-associated t umors also showed multiple comparative genomic hybridization alterations an d frequent losses of 11q (50%), and subsequent analysis of the MEN1 gene de monstrated mutations in 4 of 8 cases (50%). The adenomas from familial case s showed few alterations, and in 3 of these tumors a gain of 19p13.2-pter w as seen as the only aberration. In this study numerical copy number alterat ions were frequently detected in sporadic and irradiation-associated parath yroid adenomas, although these tumors are benign. The majority of these alt erations were found in tumors with confirmed involvement of the MEN1 gene l ocus in agreement with a role of the MEN1 gene in genomic stability. Furthe rmore, the frequent occurrence of MEN1 mutations (50%) in irradiation-assoc iated parathyroid tumors suggests that inactivation of the MEN1 gene is an important genetic alteration involved in the development of parathyroid tum ors in postirradiation patients.