TY - JOUR
T1 - MEN1 mutations in Hürthle cell (oncocytic) thyroid carcinoma
AU - Kasaian, Katayoon
AU - Chindris, Ana Maria
AU - Wiseman, Sam M.
AU - Mungall, Karen L.
AU - Zeng, Thomas
AU - Tse, Kane
AU - Schein, Jacqueline E.
AU - Rivera, Michael
AU - Necela, Brian M.
AU - Kachergus, Jennifer M.
AU - Casler, John D.
AU - Mungall, Andrew J.
AU - Moore, Richard A.
AU - Marra, Marco A.
AU - Copland, John A.
AU - Thompson, E. Aubrey
AU - Smallridge, Robert C.
AU - Jones, Steven J.M.
N1 - Publisher Copyright:
Copyright © 2015 by the Endocrine Society.
PY - 2015/4/1
Y1 - 2015/4/1
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.
AB - 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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U2 - 10.1210/jc.2014-3622
DO - 10.1210/jc.2014-3622
M3 - Article
C2 - 25625803
AN - SCOPUS:84927642742
SN - 0021-972X
VL - 100
SP - E611-E615
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 4
ER -