Familial nonsyndromic pheochromocytoma

Giuseppe Opocher, Francesca Schiavi, Maurizio Iacobone, Antonio Toniato, Sabina Sattarova, Zoran Erlic, Maddalena Martella, Caterina Mian, Isabella Merante Boschin, Laura Zambonin, Paola De Lazzari, Alessandra Murgia, Maria Rosa Pelizzo, Gennaro Favia, Franco Mantero

Research output: Chapter in Book/Report/Conference proceedingConference contribution

15 Citations (Scopus)

Abstract

Judging from recent data, heritable forms account for 30-40% of pheochromocytomas. The molecular basis for the familial pheochromocytoma has been largely elucidated and the role of germline mutation of the VHL, RET, SDHB, and SDHD genes has been established. However, on genotyping a group of 172 sporadic or familial pheochromocytomas, we characterized four unrelated probands with familial pheochromocytomas without any sequence variants of RET (exons 8, 10, 11, 13, 14, 15, and 16) or the entire coding sequence of VHL, SDHB, SDHC, SDHD, and EGLN3 (exon-intron boundaries included). The proband of family 1 is a man who had a bilateral pheochromocytoma at the age of 32 and a local recurrence at the age of 48 years. His brother died of malignant pheochromocytoma and his nephew died suddenly of an undiagnosed pheochromocytoma. The proband of family 2 is a female who had a 5-cm benign adrenal pheochromocytoma at the age of 34 years, while her cousin (maternal branch) had a monolateral pheochromocytoma at the age of 42 years. No other tumors had been reported in either family. The proband of family 3 is a female who had a bilateral pheochromocytoma at the age of 66 years. Her sister had a bilateral pheochromocytoma and breast cancer at the age of 54 years. Several other tumors were recorded in this family, including laryngeal cancer, leukemia, and a case of medullary thyroid carcinoma (MTC) in one brother. MTC was naturally ruled out in the proband and her sister. In family 4, the proband was a female who had a bilateral pheochromocytoma at the age of 46 years and a local recurrence a few years later, with liver metastases from the pheochromocytoma. Her brother had a monolateral benign pheochromocytoma. The proband also had a melanoma and bilateral renal cysts. This case revealed a VHL sequence variant IVS2 + 43 A>G, which was also found in one other unrelated sporadic pheochromocytoma. VHL mRNA integrity is currently being evaluated. The proband had no cerebellar or spinal NMR findings or retinal alterations. In family 5, the proband was a female who had a right adrenal pheochromocytoma at the age of 50 years and a breast cancer at 49 years of age. Her mother had had a right adrenal pheochromocytoma at 61 years of age. Although other molecular mechanisms, such as particular variants in untranslated regions or partial gene deletions, cannot be ruled out, we think finding families with nonsyndromic pheochromocytoma without any RET, VHL, SDHB, SDHC, SDHD, or EGLN3 mutation may argue in favor of the presence of other pheochromocytoma susceptibility genes.

Original languageEnglish
Title of host publicationAnnals of the New York Academy of Sciences
Pages149-155
Number of pages7
Volume1073
DOIs
Publication statusPublished - Aug 2006

Publication series

NameAnnals of the New York Academy of Sciences
Volume1073
ISSN (Print)00778923
ISSN (Electronic)17496632

Fingerprint

Pheochromocytoma
Genes
Tumors
Exons
Untranslated Regions
Liver
Introns
Siblings
Nuclear magnetic resonance
Messenger RNA
Islet cell tumor syndrome
Mothers
Breast Neoplasms
Recurrence
Laryngeal Neoplasms
Germ-Line Mutation
Gene Deletion
Cysts

Keywords

  • Familial pheochromocytoma
  • NF1 gene
  • RET gene
  • Succinate dehydrogenase
  • VHL gene

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Opocher, G., Schiavi, F., Iacobone, M., Toniato, A., Sattarova, S., Erlic, Z., ... Mantero, F. (2006). Familial nonsyndromic pheochromocytoma. In Annals of the New York Academy of Sciences (Vol. 1073, pp. 149-155). (Annals of the New York Academy of Sciences; Vol. 1073). https://doi.org/10.1196/annals.1353.015

Familial nonsyndromic pheochromocytoma. / Opocher, Giuseppe; Schiavi, Francesca; Iacobone, Maurizio; Toniato, Antonio; Sattarova, Sabina; Erlic, Zoran; Martella, Maddalena; Mian, Caterina; Boschin, Isabella Merante; Zambonin, Laura; De Lazzari, Paola; Murgia, Alessandra; Pelizzo, Maria Rosa; Favia, Gennaro; Mantero, Franco.

Annals of the New York Academy of Sciences. Vol. 1073 2006. p. 149-155 (Annals of the New York Academy of Sciences; Vol. 1073).

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Opocher, G, Schiavi, F, Iacobone, M, Toniato, A, Sattarova, S, Erlic, Z, Martella, M, Mian, C, Boschin, IM, Zambonin, L, De Lazzari, P, Murgia, A, Pelizzo, MR, Favia, G & Mantero, F 2006, Familial nonsyndromic pheochromocytoma. in Annals of the New York Academy of Sciences. vol. 1073, Annals of the New York Academy of Sciences, vol. 1073, pp. 149-155. https://doi.org/10.1196/annals.1353.015
Opocher G, Schiavi F, Iacobone M, Toniato A, Sattarova S, Erlic Z et al. Familial nonsyndromic pheochromocytoma. In Annals of the New York Academy of Sciences. Vol. 1073. 2006. p. 149-155. (Annals of the New York Academy of Sciences). https://doi.org/10.1196/annals.1353.015
Opocher, Giuseppe ; Schiavi, Francesca ; Iacobone, Maurizio ; Toniato, Antonio ; Sattarova, Sabina ; Erlic, Zoran ; Martella, Maddalena ; Mian, Caterina ; Boschin, Isabella Merante ; Zambonin, Laura ; De Lazzari, Paola ; Murgia, Alessandra ; Pelizzo, Maria Rosa ; Favia, Gennaro ; Mantero, Franco. / Familial nonsyndromic pheochromocytoma. Annals of the New York Academy of Sciences. Vol. 1073 2006. pp. 149-155 (Annals of the New York Academy of Sciences).
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AU - Opocher, Giuseppe

AU - Schiavi, Francesca

AU - Iacobone, Maurizio

AU - Toniato, Antonio

AU - Sattarova, Sabina

AU - Erlic, Zoran

AU - Martella, Maddalena

AU - Mian, Caterina

AU - Boschin, Isabella Merante

AU - Zambonin, Laura

AU - De Lazzari, Paola

AU - Murgia, Alessandra

AU - Pelizzo, Maria Rosa

AU - Favia, Gennaro

AU - Mantero, Franco

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N2 - Judging from recent data, heritable forms account for 30-40% of pheochromocytomas. The molecular basis for the familial pheochromocytoma has been largely elucidated and the role of germline mutation of the VHL, RET, SDHB, and SDHD genes has been established. However, on genotyping a group of 172 sporadic or familial pheochromocytomas, we characterized four unrelated probands with familial pheochromocytomas without any sequence variants of RET (exons 8, 10, 11, 13, 14, 15, and 16) or the entire coding sequence of VHL, SDHB, SDHC, SDHD, and EGLN3 (exon-intron boundaries included). The proband of family 1 is a man who had a bilateral pheochromocytoma at the age of 32 and a local recurrence at the age of 48 years. His brother died of malignant pheochromocytoma and his nephew died suddenly of an undiagnosed pheochromocytoma. The proband of family 2 is a female who had a 5-cm benign adrenal pheochromocytoma at the age of 34 years, while her cousin (maternal branch) had a monolateral pheochromocytoma at the age of 42 years. No other tumors had been reported in either family. The proband of family 3 is a female who had a bilateral pheochromocytoma at the age of 66 years. Her sister had a bilateral pheochromocytoma and breast cancer at the age of 54 years. Several other tumors were recorded in this family, including laryngeal cancer, leukemia, and a case of medullary thyroid carcinoma (MTC) in one brother. MTC was naturally ruled out in the proband and her sister. In family 4, the proband was a female who had a bilateral pheochromocytoma at the age of 46 years and a local recurrence a few years later, with liver metastases from the pheochromocytoma. Her brother had a monolateral benign pheochromocytoma. The proband also had a melanoma and bilateral renal cysts. This case revealed a VHL sequence variant IVS2 + 43 A>G, which was also found in one other unrelated sporadic pheochromocytoma. VHL mRNA integrity is currently being evaluated. The proband had no cerebellar or spinal NMR findings or retinal alterations. In family 5, the proband was a female who had a right adrenal pheochromocytoma at the age of 50 years and a breast cancer at 49 years of age. Her mother had had a right adrenal pheochromocytoma at 61 years of age. Although other molecular mechanisms, such as particular variants in untranslated regions or partial gene deletions, cannot be ruled out, we think finding families with nonsyndromic pheochromocytoma without any RET, VHL, SDHB, SDHC, SDHD, or EGLN3 mutation may argue in favor of the presence of other pheochromocytoma susceptibility genes.

AB - Judging from recent data, heritable forms account for 30-40% of pheochromocytomas. The molecular basis for the familial pheochromocytoma has been largely elucidated and the role of germline mutation of the VHL, RET, SDHB, and SDHD genes has been established. However, on genotyping a group of 172 sporadic or familial pheochromocytomas, we characterized four unrelated probands with familial pheochromocytomas without any sequence variants of RET (exons 8, 10, 11, 13, 14, 15, and 16) or the entire coding sequence of VHL, SDHB, SDHC, SDHD, and EGLN3 (exon-intron boundaries included). The proband of family 1 is a man who had a bilateral pheochromocytoma at the age of 32 and a local recurrence at the age of 48 years. His brother died of malignant pheochromocytoma and his nephew died suddenly of an undiagnosed pheochromocytoma. The proband of family 2 is a female who had a 5-cm benign adrenal pheochromocytoma at the age of 34 years, while her cousin (maternal branch) had a monolateral pheochromocytoma at the age of 42 years. No other tumors had been reported in either family. The proband of family 3 is a female who had a bilateral pheochromocytoma at the age of 66 years. Her sister had a bilateral pheochromocytoma and breast cancer at the age of 54 years. Several other tumors were recorded in this family, including laryngeal cancer, leukemia, and a case of medullary thyroid carcinoma (MTC) in one brother. MTC was naturally ruled out in the proband and her sister. In family 4, the proband was a female who had a bilateral pheochromocytoma at the age of 46 years and a local recurrence a few years later, with liver metastases from the pheochromocytoma. Her brother had a monolateral benign pheochromocytoma. The proband also had a melanoma and bilateral renal cysts. This case revealed a VHL sequence variant IVS2 + 43 A>G, which was also found in one other unrelated sporadic pheochromocytoma. VHL mRNA integrity is currently being evaluated. The proband had no cerebellar or spinal NMR findings or retinal alterations. In family 5, the proband was a female who had a right adrenal pheochromocytoma at the age of 50 years and a breast cancer at 49 years of age. Her mother had had a right adrenal pheochromocytoma at 61 years of age. Although other molecular mechanisms, such as particular variants in untranslated regions or partial gene deletions, cannot be ruled out, we think finding families with nonsyndromic pheochromocytoma without any RET, VHL, SDHB, SDHC, SDHD, or EGLN3 mutation may argue in favor of the presence of other pheochromocytoma susceptibility genes.

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