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.
Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland 20892, USA. rweil@box-r.nih.gov
R J
RJ
Weil
A O
AO
Vortmeyer
S
S
Huang
R
R
Boni
I A
IA
Lubensky
S
S
Pack
S J
SJ
Marx
Z
Z
Zhuang
E H
EH
Oldfield
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*