Malignant melanoma in patients with multiple endocrine neoplasia type 1 and involvement of the MEN1 gene in sporadic melanoma

Brita Nord, Anton Platz, Kristina Smoczynski, Soili Kytölä, Gavin Robertson, Alain Calender, Arnaud Murat, Dominique Weintraub, John Burgess, Matthew Edwards, Britt Skogseid, David Owen, Norman Lassam, David Hogg, Catharina Larsson, Bin Tean Teh

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Abstract

Multiple endocrine neoplasia type 1 (MEN 1) is a familial cancer syndrome associated primarily with endocrine tumors of the parathyroids, enteropancreas and anterior pituitary. However, tumors of mesenchymal origin such as angiofibroma and collagenoma of the skin have also been associated with the syndrome. This highlights the possibility of an association between MEN 1 and some other types of tumors. Here we report 7 cases of primary malignant melanoma occurring in 7 MEN 1 families, all patients exhibiting classic features of MEN 1. Based on these findings and the previous implication of multiple melanoma tumor suppressor(s) in 11q, including the MEN 1 region, we have investigated the involvement of the MEN 1 gene in melanoma tumorigenesis. Mutation analysis was performed on a panel of 39 sporadic metastatic melanomas, 13 melanoma cell lines and 20 melanoma families without CDKN2A or CDK4 germline mutations. In addition, 19 sporadic metastatic tumors were screened for loss of heterozygosity (LOH) in 11q13. LOH was detected in 6 tumors (32%), and in 4 of the tumors the pattern of LOH suggested that the deletion included the MEN1 gene locus. A novel somatic nonsense mutation in exon 7 (Q349X) was identified in 1 sporadic tumor which also showed loss of the wild-type allele. We conclude that the MEN1 gene plays a role in the tumorigenesis of a small subgroup of melanoma. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish (US)
Pages (from-to)463-467
Number of pages5
JournalInternational Journal of Cancer
Volume87
Issue number4
DOIs
StatePublished - Sep 2 2000

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Multiple Endocrine Neoplasia Type 1
Melanoma
Genes
Neoplasms
Loss of Heterozygosity
Carcinogenesis
Angiofibroma
Germ-Line Mutation
Nonsense Codon
Exons
Alleles
Cell Line
Skin
Mutation

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Nord, Brita ; Platz, Anton ; Smoczynski, Kristina ; Kytölä, Soili ; Robertson, Gavin ; Calender, Alain ; Murat, Arnaud ; Weintraub, Dominique ; Burgess, John ; Edwards, Matthew ; Skogseid, Britt ; Owen, David ; Lassam, Norman ; Hogg, David ; Larsson, Catharina ; Teh, Bin Tean. / Malignant melanoma in patients with multiple endocrine neoplasia type 1 and involvement of the MEN1 gene in sporadic melanoma. In: International Journal of Cancer. 2000 ; Vol. 87, No. 4. pp. 463-467.
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abstract = "Multiple endocrine neoplasia type 1 (MEN 1) is a familial cancer syndrome associated primarily with endocrine tumors of the parathyroids, enteropancreas and anterior pituitary. However, tumors of mesenchymal origin such as angiofibroma and collagenoma of the skin have also been associated with the syndrome. This highlights the possibility of an association between MEN 1 and some other types of tumors. Here we report 7 cases of primary malignant melanoma occurring in 7 MEN 1 families, all patients exhibiting classic features of MEN 1. Based on these findings and the previous implication of multiple melanoma tumor suppressor(s) in 11q, including the MEN 1 region, we have investigated the involvement of the MEN 1 gene in melanoma tumorigenesis. Mutation analysis was performed on a panel of 39 sporadic metastatic melanomas, 13 melanoma cell lines and 20 melanoma families without CDKN2A or CDK4 germline mutations. In addition, 19 sporadic metastatic tumors were screened for loss of heterozygosity (LOH) in 11q13. LOH was detected in 6 tumors (32{\%}), and in 4 of the tumors the pattern of LOH suggested that the deletion included the MEN1 gene locus. A novel somatic nonsense mutation in exon 7 (Q349X) was identified in 1 sporadic tumor which also showed loss of the wild-type allele. We conclude that the MEN1 gene plays a role in the tumorigenesis of a small subgroup of melanoma. (C) 2000 Wiley-Liss, Inc.",
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Nord, B, Platz, A, Smoczynski, K, Kytölä, S, Robertson, G, Calender, A, Murat, A, Weintraub, D, Burgess, J, Edwards, M, Skogseid, B, Owen, D, Lassam, N, Hogg, D, Larsson, C & Teh, BT 2000, 'Malignant melanoma in patients with multiple endocrine neoplasia type 1 and involvement of the MEN1 gene in sporadic melanoma', International Journal of Cancer, vol. 87, no. 4, pp. 463-467. https://doi.org/10.1002/1097-0215(20000815)87:4<463::AID-IJC1>3.0.CO;2-8

Malignant melanoma in patients with multiple endocrine neoplasia type 1 and involvement of the MEN1 gene in sporadic melanoma. / Nord, Brita; Platz, Anton; Smoczynski, Kristina; Kytölä, Soili; Robertson, Gavin; Calender, Alain; Murat, Arnaud; Weintraub, Dominique; Burgess, John; Edwards, Matthew; Skogseid, Britt; Owen, David; Lassam, Norman; Hogg, David; Larsson, Catharina; Teh, Bin Tean.

In: International Journal of Cancer, Vol. 87, No. 4, 02.09.2000, p. 463-467.

Research output: Contribution to journalArticle

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T1 - Malignant melanoma in patients with multiple endocrine neoplasia type 1 and involvement of the MEN1 gene in sporadic melanoma

AU - Nord, Brita

AU - Platz, Anton

AU - Smoczynski, Kristina

AU - Kytölä, Soili

AU - Robertson, Gavin

AU - Calender, Alain

AU - Murat, Arnaud

AU - Weintraub, Dominique

AU - Burgess, John

AU - Edwards, Matthew

AU - Skogseid, Britt

AU - Owen, David

AU - Lassam, Norman

AU - Hogg, David

AU - Larsson, Catharina

AU - Teh, Bin Tean

PY - 2000/9/2

Y1 - 2000/9/2

N2 - Multiple endocrine neoplasia type 1 (MEN 1) is a familial cancer syndrome associated primarily with endocrine tumors of the parathyroids, enteropancreas and anterior pituitary. However, tumors of mesenchymal origin such as angiofibroma and collagenoma of the skin have also been associated with the syndrome. This highlights the possibility of an association between MEN 1 and some other types of tumors. Here we report 7 cases of primary malignant melanoma occurring in 7 MEN 1 families, all patients exhibiting classic features of MEN 1. Based on these findings and the previous implication of multiple melanoma tumor suppressor(s) in 11q, including the MEN 1 region, we have investigated the involvement of the MEN 1 gene in melanoma tumorigenesis. Mutation analysis was performed on a panel of 39 sporadic metastatic melanomas, 13 melanoma cell lines and 20 melanoma families without CDKN2A or CDK4 germline mutations. In addition, 19 sporadic metastatic tumors were screened for loss of heterozygosity (LOH) in 11q13. LOH was detected in 6 tumors (32%), and in 4 of the tumors the pattern of LOH suggested that the deletion included the MEN1 gene locus. A novel somatic nonsense mutation in exon 7 (Q349X) was identified in 1 sporadic tumor which also showed loss of the wild-type allele. We conclude that the MEN1 gene plays a role in the tumorigenesis of a small subgroup of melanoma. (C) 2000 Wiley-Liss, Inc.

AB - Multiple endocrine neoplasia type 1 (MEN 1) is a familial cancer syndrome associated primarily with endocrine tumors of the parathyroids, enteropancreas and anterior pituitary. However, tumors of mesenchymal origin such as angiofibroma and collagenoma of the skin have also been associated with the syndrome. This highlights the possibility of an association between MEN 1 and some other types of tumors. Here we report 7 cases of primary malignant melanoma occurring in 7 MEN 1 families, all patients exhibiting classic features of MEN 1. Based on these findings and the previous implication of multiple melanoma tumor suppressor(s) in 11q, including the MEN 1 region, we have investigated the involvement of the MEN 1 gene in melanoma tumorigenesis. Mutation analysis was performed on a panel of 39 sporadic metastatic melanomas, 13 melanoma cell lines and 20 melanoma families without CDKN2A or CDK4 germline mutations. In addition, 19 sporadic metastatic tumors were screened for loss of heterozygosity (LOH) in 11q13. LOH was detected in 6 tumors (32%), and in 4 of the tumors the pattern of LOH suggested that the deletion included the MEN1 gene locus. A novel somatic nonsense mutation in exon 7 (Q349X) was identified in 1 sporadic tumor which also showed loss of the wild-type allele. We conclude that the MEN1 gene plays a role in the tumorigenesis of a small subgroup of melanoma. (C) 2000 Wiley-Liss, Inc.

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