MEN1 mutations in Hürthle cell (oncocytic) thyroid carcinoma

Katayoon Kasaian, Ana Maria Chindris, Sam M. Wiseman, Karen L. Mungall, Thomas Zeng, Kane Tse, Jacqueline E. Schein, Michael Rivera, Brian M. Necela, Jennifer M. Kachergus, John D. Casler, Andrew J. Mungall, Richard A. Moore, Marco A. Marra, John A III Copland, E Aubrey Thompson, Robert Christian Smallridge, Steven J M Jones

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Context and Objective: Oncocytic thyroid carcinoma, alsoknownas Hürthle cell thyroid carcinoma, accounts for only a small percentage of all thyroid cancers. However, this malignancy often presents at an advanced stage and poses unique challenges to patients and clinicians. Surgical resection of the tumor accompanied in some cases by radioactive iodine treatment, radiation, and chemotherapy are the established modes of therapy. Knowledge of the perturbed oncogenic pathways can provide better understanding of the mechanism of disease and thus opportunities for more effective clinical management. Design and Patients: Initially, two oncocytic thyroid carcinomas and their matched normal tissues were profiled using whole genome sequencing. Subsequently, 72 oncocytic thyroid carcinomas, one cell line, and five Hürthle cell adenomas were examined by targeted sequencing for the presence of mutations in the multiple endocrine neoplasia I (MEN1) gene. Results: Here we report the identification of MEN1 loss-of-function mutations in 4% of patients diagnosed with oncocytic thyroid carcinoma. Whole genome sequence data also revealed large regions of copy number variation encompassing nearly the entire genomes of these tumors. Conclusion: Menin, a ubiquitously expressed nuclear protein, is a well-characterized tumor suppressor whose loss is the cause of MEN1 syndrome. Menin is involved in several major cellular pathways such as regulation of transcription, control of cell cycle, apoptosis, and DNA damage repair pathways. Mutations of this gene in a subset of Hürthle cell tumors point to a potential role for this protein and its associated pathways in thyroid tumorigenesis.

Original languageEnglish (US)
Pages (from-to)E611-E615
JournalJournal of Clinical Endocrinology and Metabolism
Volume100
Issue number4
DOIs
StatePublished - Apr 1 2015

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Multiple Endocrine Neoplasia Type 1
Thyroid Neoplasms
Genes
Tumors
Mutation
Genome
Neoplasms
Cells
Chemotherapy
Multiple Endocrine Neoplasia
Transcription
Nuclear Proteins
Iodine
Cell Cycle Checkpoints
Repair
DNA Repair
Adenoma
DNA Damage
Tissue
Apoptosis

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

Kasaian, K., Chindris, A. M., Wiseman, S. M., Mungall, K. L., Zeng, T., Tse, K., ... Jones, S. J. M. (2015). MEN1 mutations in Hürthle cell (oncocytic) thyroid carcinoma. Journal of Clinical Endocrinology and Metabolism, 100(4), E611-E615. https://doi.org/10.1210/jc.2014-3622

MEN1 mutations in Hürthle cell (oncocytic) thyroid carcinoma. / Kasaian, Katayoon; Chindris, Ana Maria; Wiseman, Sam M.; Mungall, Karen L.; Zeng, Thomas; Tse, Kane; Schein, Jacqueline E.; Rivera, Michael; Necela, Brian M.; Kachergus, Jennifer M.; Casler, John D.; Mungall, Andrew J.; Moore, Richard A.; Marra, Marco A.; Copland, John A III; Thompson, E Aubrey; Smallridge, Robert Christian; Jones, Steven J M.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 100, No. 4, 01.04.2015, p. E611-E615.

Research output: Contribution to journalArticle

Kasaian, K, Chindris, AM, Wiseman, SM, Mungall, KL, Zeng, T, Tse, K, Schein, JE, Rivera, M, Necela, BM, Kachergus, JM, Casler, JD, Mungall, AJ, Moore, RA, Marra, MA, Copland, JAIII, Thompson, EA, Smallridge, RC & Jones, SJM 2015, 'MEN1 mutations in Hürthle cell (oncocytic) thyroid carcinoma', Journal of Clinical Endocrinology and Metabolism, vol. 100, no. 4, pp. E611-E615. https://doi.org/10.1210/jc.2014-3622
Kasaian K, Chindris AM, Wiseman SM, Mungall KL, Zeng T, Tse K et al. MEN1 mutations in Hürthle cell (oncocytic) thyroid carcinoma. Journal of Clinical Endocrinology and Metabolism. 2015 Apr 1;100(4):E611-E615. https://doi.org/10.1210/jc.2014-3622
Kasaian, Katayoon ; Chindris, Ana Maria ; Wiseman, Sam M. ; Mungall, Karen L. ; Zeng, Thomas ; Tse, Kane ; Schein, Jacqueline E. ; Rivera, Michael ; Necela, Brian M. ; Kachergus, Jennifer M. ; Casler, John D. ; Mungall, Andrew J. ; Moore, Richard A. ; Marra, Marco A. ; Copland, John A III ; Thompson, E Aubrey ; Smallridge, Robert Christian ; Jones, Steven J M. / MEN1 mutations in Hürthle cell (oncocytic) thyroid carcinoma. In: Journal of Clinical Endocrinology and Metabolism. 2015 ; Vol. 100, No. 4. pp. E611-E615.
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N2 - Context and Objective: Oncocytic thyroid carcinoma, alsoknownas Hürthle cell thyroid carcinoma, accounts for only a small percentage of all thyroid cancers. However, this malignancy often presents at an advanced stage and poses unique challenges to patients and clinicians. Surgical resection of the tumor accompanied in some cases by radioactive iodine treatment, radiation, and chemotherapy are the established modes of therapy. Knowledge of the perturbed oncogenic pathways can provide better understanding of the mechanism of disease and thus opportunities for more effective clinical management. Design and Patients: Initially, two oncocytic thyroid carcinomas and their matched normal tissues were profiled using whole genome sequencing. Subsequently, 72 oncocytic thyroid carcinomas, one cell line, and five Hürthle cell adenomas were examined by targeted sequencing for the presence of mutations in the multiple endocrine neoplasia I (MEN1) gene. Results: Here we report the identification of MEN1 loss-of-function mutations in 4% of patients diagnosed with oncocytic thyroid carcinoma. Whole genome sequence data also revealed large regions of copy number variation encompassing nearly the entire genomes of these tumors. Conclusion: Menin, a ubiquitously expressed nuclear protein, is a well-characterized tumor suppressor whose loss is the cause of MEN1 syndrome. Menin is involved in several major cellular pathways such as regulation of transcription, control of cell cycle, apoptosis, and DNA damage repair pathways. Mutations of this gene in a subset of Hürthle cell tumors point to a potential role for this protein and its associated pathways in thyroid tumorigenesis.

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