11q13 allelic loss in pituitary tumors in patients with multiple endocrine neoplasia syndrome type 1.
Pituitary adenomas may develop sporadically or as part of the multiple endocrine neoplasia type 1 (MEN 1) syndrome. The gene responsible for MEN 1 syndrome was recently identified and cloned. Low rates of MEN 1 gene mutations and deletions have been reported in sporadic pituitary adenomas. To elucidate the role of the MEN 1 gene in the pathogenesis of MEN 1-associated pituitary tumors, we examined pituitary adenomas from 11 MEN 1 patients for the presence of 11q13 allelic loss. Ten of the 11 pituitary tumors were informative by PCR-based loss of heterozygosity analysis. Using a combination of family pedigree analysis and restriction analysis directed at the mutated allele in 8 of the 10 informative cases, it was demonstrated in all 8 cases that it is the wild-type allele that undergoes deletion. All 11 tumors, 4 of which were growth hormone secreting, were additionally analyzed for mutation in the Gs alpha subunit (gsp) gene. None of the tumors (0 of 11 tumors) revealed a gsp gene mutation. Therefore, genetic alterations of the MEN 1 gene seem to play a dominant role in MEN 1-associated pituitary tumorigenesis, whereas gsp gene mutations do not seem to be a frequent event in either growth hormone-secreting or other types of MEN 1-associated pituitary tumors. These results suggest that MEN 1-associated pituitary tumors develop via genetic pathways that differ from those of most sporadic pituitary tumors.
Weil
R J
RJ
Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland 20892, USA. rweil@box-r.nih.gov
Vortmeyer
A O
AO
Huang
S
S
Boni
R
R
Lubensky
I A
IA
Pack
S
S
Marx
S J
SJ
Zhuang
Z
Z
Oldfield
E H
EH
D000236:Adenoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000483:Alleles; D002675:Child, Preschool; D005260:Female; D017353:Gene Deletion; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics*; D010911:Pituitary Neoplasms / Q000235:genetics*