title: Alternative genetic pathways in parathyroid tumorigenesis.
abstract: In this study 44 parathyroid tumors from 26 sporadic cases, 10 cases previously given irradiation to the neck, and 8 familial cases were screened for sequence copy number alterations by comparative genomic hybridization. In the sporadic adenomas, commonly occurring minimal regions of loss could be defined to chromosome 11 (38%), 15q15-qter (27%), and 1p34-pter (19%), whereas gains preferentially involved 19p13.2-pter (15%) and 7pter-qter (12%). Multiple aberrations were found in sporadic tumors with a somatic mutation and/or loss of heterozygosity of the MEN1 gene. The irradiation-associated tumors also showed multiple comparative genomic hybridization alterations and frequent losses of 11q (50%), and subsequent analysis of the MEN1 gene demonstrated mutations in 4 of 8 cases (50%). The adenomas from familial cases showed few alterations, and in 3 of these tumors a gain of 19p13.2-pter was seen as the only aberration. In this study numerical copy number alterations were frequently detected in sporadic and irradiation-associated parathyroid adenomas, although these tumors are benign. The majority of these alterations were found in tumors with confirmed involvement of the MEN1 gene locus in agreement with a role of the MEN1 gene in genomic stability. Furthermore, the frequent occurrence of MEN1 mutations (50%) in irradiation-associated parathyroid tumors suggests that inactivation of the MEN1 gene is an important genetic alteration involved in the development of parathyroid tumors in postirradiation patients.
authors.affiliation: Department of Molecular Medicine Endocrine Tumor Unit, Karolinska Hospital, Stockholm, Sweden.
authors.forename: F
authors.initials: F
authors.lastname: Farnebo
authors.forename: S
authors.initials: S
authors.lastname: Kytölä
authors.forename: B T
authors.initials: BT
authors.lastname: Teh
authors.forename: T
authors.initials: T
authors.lastname: Dwight
authors.forename: F K
authors.initials: FK
authors.lastname: Wong
authors.forename: A
authors.initials: A
authors.lastname: Höög
authors.forename: M
authors.initials: M
authors.lastname: Elvius
authors.forename: W S
authors.initials: WS
authors.lastname: Wassif
authors.forename: N W
authors.initials: NW
authors.lastname: Thompson
authors.forename: L O
authors.initials: LO
authors.lastname: Farnebo
authors.forename: K
authors.initials: K
authors.lastname: Sandelin
authors.forename: C
authors.initials: C
authors.lastname: Larsson
mesh_terms: D000236:Adenoma / Q000235:genetics; D000328:Adult; D000368:Aged; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009333:Neck / Q000528:radiation effects; D009381:Neoplasms, Radiation-Induced / Q000235:genetics; D009693:Nucleic Acid Hybridization; D010282:Parathyroid Neoplasms / Q000235:genetics*