Alternative genetic pathways in parathyroid tumorigenesis.
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.
Farnebo
F
F
Department of Molecular Medicine Endocrine Tumor Unit, Karolinska Hospital, Stockholm, Sweden.
Kytölä
S
S
Teh
B T
BT
Dwight
T
T
Wong
F K
FK
Höög
A
A
Elvius
M
M
Wassif
W S
WS
Thompson
N W
NW
Farnebo
L O
LO
Sandelin
K
K
Larsson
C
C
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*