Somatic mutation of the MEN1 gene in parathyroid tumours

C. Heppner, M. B. Kester, S. K. Agarwal, L. V. Debelenko, M. R. Emmert-Buck, S. C. Guru, P. Manickam, S. E. Olufemi, M. C. Skarulis, J. L. Doppman, R. H. Alexander, Y. S. Kim, S. K. Saggar, I. A. Lubensky, Z. Zhuang, L. A. Liotta, S. C. Chandrasekharappa, F. S. Collins, Allen M. Spiegel, A. L. BurnsS. J. Marx

Research output: Contribution to journalArticle

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Abstract

Primary hyperparathyroidism is a common disorder with an annual incidencce of approximately 0.5 in 1,000 (ref. 1). In more than 95% of cases, the disease is caused by sporadic parathyroid adenoma or sporadic hyperplasia. Some cases are caused by inherited syndromes, such as multiple endocrine neoplasia type 1 (MEN1; ref. 2). In most cases, the molecular basis of parathyroid neoplasia is unknown. Parathyroid adenomas are usually monoclonal, suggesting that one important step in tumour development is a mutation in a progenitor cell. Approximately 30% of sporadic parathyroid turnouts show loss of heterozygosity (LOH) for polymorphic markers on 11q13, the site of the MEN1 tumour suppressor gene. This raises the question of whether such sporadic parathyroid tumours are caused by sequential inactivation of both alleles of the MEN1 gene. We recently cloned the MEN1 gene and identified MEN1 germline mutations in fourteen of fifteen kindreds with familial MEN1 (ref. 10). We have studied parathyroid tumours not associated with MEN1 to determine whether somatic mutations in the MEN1 gene are present. Among 33 tumours we found somatic MEN1 gene mutation in 7, white the corresponding MEN1 germline sequence was normal in each patient. All tumours with MEN1 gene mutation showed LOH on 11q13, making the tumour cells hemi- or homozygous for the mutant allele. Thus, somatic MEN1 gene mutation contributes to tumorigenesis in a substantial number of parathyroid tumours not associated with the MEN1 syndrome.

Original languageEnglish (US)
Pages (from-to)375-378
Number of pages4
JournalNature Genetics
Volume16
Issue number4
DOIs
StatePublished - 1997
Externally publishedYes

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Multiple Endocrine Neoplasia Type 1
Mutation
Genes
Neoplasms
Parathyroid Neoplasms
Loss of Heterozygosity
Alleles
Primary Hyperparathyroidism
Germ-Line Mutation
Tumor Suppressor Genes

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Heppner, C., Kester, M. B., Agarwal, S. K., Debelenko, L. V., Emmert-Buck, M. R., Guru, S. C., ... Marx, S. J. (1997). Somatic mutation of the MEN1 gene in parathyroid tumours. Nature Genetics, 16(4), 375-378. https://doi.org/10.1038/ng0897-375

Somatic mutation of the MEN1 gene in parathyroid tumours. / Heppner, C.; Kester, M. B.; Agarwal, S. K.; Debelenko, L. V.; Emmert-Buck, M. R.; Guru, S. C.; Manickam, P.; Olufemi, S. E.; Skarulis, M. C.; Doppman, J. L.; Alexander, R. H.; Kim, Y. S.; Saggar, S. K.; Lubensky, I. A.; Zhuang, Z.; Liotta, L. A.; Chandrasekharappa, S. C.; Collins, F. S.; Spiegel, Allen M.; Burns, A. L.; Marx, S. J.

In: Nature Genetics, Vol. 16, No. 4, 1997, p. 375-378.

Research output: Contribution to journalArticle

Heppner, C, Kester, MB, Agarwal, SK, Debelenko, LV, Emmert-Buck, MR, Guru, SC, Manickam, P, Olufemi, SE, Skarulis, MC, Doppman, JL, Alexander, RH, Kim, YS, Saggar, SK, Lubensky, IA, Zhuang, Z, Liotta, LA, Chandrasekharappa, SC, Collins, FS, Spiegel, AM, Burns, AL & Marx, SJ 1997, 'Somatic mutation of the MEN1 gene in parathyroid tumours', Nature Genetics, vol. 16, no. 4, pp. 375-378. https://doi.org/10.1038/ng0897-375
Heppner C, Kester MB, Agarwal SK, Debelenko LV, Emmert-Buck MR, Guru SC et al. Somatic mutation of the MEN1 gene in parathyroid tumours. Nature Genetics. 1997;16(4):375-378. https://doi.org/10.1038/ng0897-375
Heppner, C. ; Kester, M. B. ; Agarwal, S. K. ; Debelenko, L. V. ; Emmert-Buck, M. R. ; Guru, S. C. ; Manickam, P. ; Olufemi, S. E. ; Skarulis, M. C. ; Doppman, J. L. ; Alexander, R. H. ; Kim, Y. S. ; Saggar, S. K. ; Lubensky, I. A. ; Zhuang, Z. ; Liotta, L. A. ; Chandrasekharappa, S. C. ; Collins, F. S. ; Spiegel, Allen M. ; Burns, A. L. ; Marx, S. J. / Somatic mutation of the MEN1 gene in parathyroid tumours. In: Nature Genetics. 1997 ; Vol. 16, No. 4. pp. 375-378.
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abstract = "Primary hyperparathyroidism is a common disorder with an annual incidencce of approximately 0.5 in 1,000 (ref. 1). In more than 95{\%} of cases, the disease is caused by sporadic parathyroid adenoma or sporadic hyperplasia. Some cases are caused by inherited syndromes, such as multiple endocrine neoplasia type 1 (MEN1; ref. 2). In most cases, the molecular basis of parathyroid neoplasia is unknown. Parathyroid adenomas are usually monoclonal, suggesting that one important step in tumour development is a mutation in a progenitor cell. Approximately 30{\%} of sporadic parathyroid turnouts show loss of heterozygosity (LOH) for polymorphic markers on 11q13, the site of the MEN1 tumour suppressor gene. This raises the question of whether such sporadic parathyroid tumours are caused by sequential inactivation of both alleles of the MEN1 gene. We recently cloned the MEN1 gene and identified MEN1 germline mutations in fourteen of fifteen kindreds with familial MEN1 (ref. 10). We have studied parathyroid tumours not associated with MEN1 to determine whether somatic mutations in the MEN1 gene are present. Among 33 tumours we found somatic MEN1 gene mutation in 7, white the corresponding MEN1 germline sequence was normal in each patient. All tumours with MEN1 gene mutation showed LOH on 11q13, making the tumour cells hemi- or homozygous for the mutant allele. Thus, somatic MEN1 gene mutation contributes to tumorigenesis in a substantial number of parathyroid tumours not associated with the MEN1 syndrome.",
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T1 - Somatic mutation of the MEN1 gene in parathyroid tumours

AU - Heppner, C.

AU - Kester, M. B.

AU - Agarwal, S. K.

AU - Debelenko, L. V.

AU - Emmert-Buck, M. R.

AU - Guru, S. C.

AU - Manickam, P.

AU - Olufemi, S. E.

AU - Skarulis, M. C.

AU - Doppman, J. L.

AU - Alexander, R. H.

AU - Kim, Y. S.

AU - Saggar, S. K.

AU - Lubensky, I. A.

AU - Zhuang, Z.

AU - Liotta, L. A.

AU - Chandrasekharappa, S. C.

AU - Collins, F. S.

AU - Spiegel, Allen M.

AU - Burns, A. L.

AU - Marx, S. J.

PY - 1997

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N2 - Primary hyperparathyroidism is a common disorder with an annual incidencce of approximately 0.5 in 1,000 (ref. 1). In more than 95% of cases, the disease is caused by sporadic parathyroid adenoma or sporadic hyperplasia. Some cases are caused by inherited syndromes, such as multiple endocrine neoplasia type 1 (MEN1; ref. 2). In most cases, the molecular basis of parathyroid neoplasia is unknown. Parathyroid adenomas are usually monoclonal, suggesting that one important step in tumour development is a mutation in a progenitor cell. Approximately 30% of sporadic parathyroid turnouts show loss of heterozygosity (LOH) for polymorphic markers on 11q13, the site of the MEN1 tumour suppressor gene. This raises the question of whether such sporadic parathyroid tumours are caused by sequential inactivation of both alleles of the MEN1 gene. We recently cloned the MEN1 gene and identified MEN1 germline mutations in fourteen of fifteen kindreds with familial MEN1 (ref. 10). We have studied parathyroid tumours not associated with MEN1 to determine whether somatic mutations in the MEN1 gene are present. Among 33 tumours we found somatic MEN1 gene mutation in 7, white the corresponding MEN1 germline sequence was normal in each patient. All tumours with MEN1 gene mutation showed LOH on 11q13, making the tumour cells hemi- or homozygous for the mutant allele. Thus, somatic MEN1 gene mutation contributes to tumorigenesis in a substantial number of parathyroid tumours not associated with the MEN1 syndrome.

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