The parathyroid/pituitary variant of multiple endocrine neoplasia type 1 usually has causes other than p27Kip1 mutations

Atsushi Ozawa, Sunita K. Agarwal, Carmen M. Mateo, A. Lee Burns, Terri S. Rice, Patricia A. Kennedy, Caitlin M. Quigley, William F. Simonds, Lee S. Weinstein, Settara C. Chandrasekharappa, Francis S. Collins, Allen M. Spiegel, Stephen J. Marx

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Context: 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 p27Kip1/CDKN1B. Objective: The objective was to test p27 in germline DNA from cases with tumors of both the parathyroids and pituitary. Design: Medical record review and sequence analysis in DNA were performed. Setting: This study involved an inpatient and outpatient referral program for cases of endocrine tumors. Patients: 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. Interventions: 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. Main Outcome Measures: 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).

Original languageEnglish (US)
Pages (from-to)1948-1951
Number of pages4
JournalJournal of Clinical Endocrinology and Metabolism
Volume92
Issue number5
DOIs
StatePublished - May 2007
Externally publishedYes

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Multiple Endocrine Neoplasia Type 1
Tumors
Mutation
Neoplasms
Germ-Line Mutation
DNA Sequence Analysis
DNA
Genes
Pituitary Neoplasms
Polymorphism
Medical Records
Inpatients
Outpatients
Referral and Consultation
Nucleotides
Outcome Assessment (Health Care)
Substitution reactions
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

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The parathyroid/pituitary variant of multiple endocrine neoplasia type 1 usually has causes other than p27Kip1 mutations. / Ozawa, Atsushi; Agarwal, Sunita K.; Mateo, Carmen M.; Burns, A. Lee; Rice, Terri S.; Kennedy, Patricia A.; Quigley, Caitlin M.; Simonds, William F.; Weinstein, Lee S.; Chandrasekharappa, Settara C.; Collins, Francis S.; Spiegel, Allen M.; Marx, Stephen J.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 92, No. 5, 05.2007, p. 1948-1951.

Research output: Contribution to journalArticle

Ozawa, A, Agarwal, SK, Mateo, CM, Burns, AL, Rice, TS, Kennedy, PA, Quigley, CM, Simonds, WF, Weinstein, LS, Chandrasekharappa, SC, Collins, FS, Spiegel, AM & Marx, SJ 2007, 'The parathyroid/pituitary variant of multiple endocrine neoplasia type 1 usually has causes other than p27Kip1 mutations', Journal of Clinical Endocrinology and Metabolism, vol. 92, no. 5, pp. 1948-1951. https://doi.org/10.1210/jc.2006-2563
Ozawa, Atsushi ; Agarwal, Sunita K. ; Mateo, Carmen M. ; Burns, A. Lee ; Rice, Terri S. ; Kennedy, Patricia A. ; Quigley, Caitlin M. ; Simonds, William F. ; Weinstein, Lee S. ; Chandrasekharappa, Settara C. ; Collins, Francis S. ; Spiegel, Allen M. ; Marx, Stephen J. / The parathyroid/pituitary variant of multiple endocrine neoplasia type 1 usually has causes other than p27Kip1 mutations. In: Journal of Clinical Endocrinology and Metabolism. 2007 ; Vol. 92, No. 5. pp. 1948-1951.
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abstract = "Context: 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 p27Kip1/CDKN1B. Objective: The objective was to test p27 in germline DNA from cases with tumors of both the parathyroids and pituitary. Design: Medical record review and sequence analysis in DNA were performed. Setting: This study involved an inpatient and outpatient referral program for cases of endocrine tumors. Patients: 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. Interventions: 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. Main Outcome Measures: 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).",
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T1 - The parathyroid/pituitary variant of multiple endocrine neoplasia type 1 usually has causes other than p27Kip1 mutations

AU - Ozawa, Atsushi

AU - Agarwal, Sunita K.

AU - Mateo, Carmen M.

AU - Burns, A. Lee

AU - Rice, Terri S.

AU - Kennedy, Patricia A.

AU - Quigley, Caitlin M.

AU - Simonds, William F.

AU - Weinstein, Lee S.

AU - Chandrasekharappa, Settara C.

AU - Collins, Francis S.

AU - Spiegel, Allen M.

AU - Marx, Stephen J.

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N2 - Context: 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 p27Kip1/CDKN1B. Objective: The objective was to test p27 in germline DNA from cases with tumors of both the parathyroids and pituitary. Design: Medical record review and sequence analysis in DNA were performed. Setting: This study involved an inpatient and outpatient referral program for cases of endocrine tumors. Patients: 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. Interventions: 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. Main Outcome Measures: 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).

AB - Context: 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 p27Kip1/CDKN1B. Objective: The objective was to test p27 in germline DNA from cases with tumors of both the parathyroids and pituitary. Design: Medical record review and sequence analysis in DNA were performed. Setting: This study involved an inpatient and outpatient referral program for cases of endocrine tumors. Patients: 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. Interventions: 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. Main Outcome Measures: 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).

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