The parathyroid/pituitary variant of multiple endocrine neoplasia type 1 usually has causes other than p27Kip1 mutations.
BACKGROUND
One variant of multiple endocrine neoplasia type 1 (MEN1) is defined by sporadic tumors of both the parathyroids and pituitary. The prevalence of identified MEN1 mutations in this variant is lower than in familial MEN1 (7% vs. 90%), suggesting different causes. Recently, one case of this variant had a germline mutation of p27(Kip1)/CDKN1B.


OBJECTIVE
The objective was to test p27 in germline DNA from cases with tumors of both the parathyroids and pituitary.


METHODS
Medical record review and sequence analysis in DNA were performed.


METHODS
This study involved an inpatient and outpatient referral program for cases of endocrine tumors.


METHODS
Sixteen index cases had sporadic tumors of two organs, both the parathyroids and the pituitary. There were 18 additional index cases with related features of familial tumors. Five subjects were normal controls. No case had an identified MEN1 mutation.


METHODS
Clinical status of endocrine tumors was tabulated. Sequencing of germline DNA from index cases and control cases for the p27 gene was performed by PCR.


METHODS
Endocrine tumor types and their expressions were measured, as were sequence changes in the p27 gene.


RESULTS
Tumor features were documented in index cases and families. One p27 germline single nucleotide change was identified. This predicted a silent substitution of Thr142Thr. Furthermore, there was a normal prevalence of heterozygosity for a common p27 polymorphism, making a large p27 deletion unlikely in all or most of these cases.


CONCLUSIONS
The MEN1 variant with sporadic parathyroid tumors, sporadic pituitary tumor, and no identified MEN1 mutation is usually not caused by p27 germline mutations. It is usually caused by as yet unknown process(es).
Ozawa
Atsushi
A
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1802, USA. ozawaa@niddk.nih.gov
Agarwal
Sunita K
SK
Mateo
Carmen M
CM
Burns
A Lee
AL
Rice
Terri S
TS
Kennedy
Patricia A
PA
Quigley
Caitlin M
CM
Simonds
William F
WF
Weinstein
Lee S
LS
Chandrasekharappa
Settara C
SC
Collins
Francis S
FS
Spiegel
Allen M
AM
Marx
Stephen J
SJ
D000328:Adult; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D018095:Germ-Line Mutation / Q000235:genetics; D006728:Hormones / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics*; D010282:Parathyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic / Q000235:genetics
D004273:DNA, Neoplasm; D006728:Hormones; D050760:Cyclin-Dependent Kinase Inhibitor p27