title: MEN1 mutations in Hürthle cell (oncocytic) thyroid carcinoma.
abstract: OBJECTIVE
  Oncocytic thyroid carcinoma, also known as 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Canada's Michael Smith Genome Sciences Centre (K.K., K.L.M., T.Z., K.T., J.E.S., A.J.M., R.A.M., M.A.M., S.J.M.J.), BC Cancer Agency, Vancouver, V5Z 4S6 Canada; Department of Otorhinolaryngology-Head and Neck Surgery (A.-M.C., J.D.C.), Mayo Clinic, Jacksonville, Florida 32224; Department of Surgery (S.M.W.), St. Paul's Hospital and University of British Columbia, Vancouver, V6Z 1Y6 Canada; Department of Laboratory Medicine and Pathology (M.R.), Mayo Clinic, Rochester, Minnesota 55905; Department of Cancer Biology (B.M.N., J.M.K., J.A.C., E.A.T., R.C.S.), Mayo Clinic, Jacksonville, Florida 32224; Department of Medical Genetics (M.A.M., S.J.M.J.), University of British Columbia, Vancouver, V6T 1Z4 Canada; Department of Medicine, Division of Endocrinology and Metabolism (R.C.S.), Mayo Clinic, Jacksonville, Florida 32224; and Department of Molecular Biology and Biochemistry (S.J.M.J.), Simon Fraser University, Burnaby, V5A 1S6 Canada.
authors.forename: Katayoon
authors.initials: K
authors.lastname: Kasaian
authors.forename: Ana-Maria
authors.initials: AM
authors.lastname: Chindris
authors.forename: Sam M
authors.initials: SM
authors.lastname: Wiseman
authors.forename: Karen L
authors.initials: KL
authors.lastname: Mungall
authors.forename: Thomas
authors.initials: T
authors.lastname: Zeng
authors.forename: Kane
authors.initials: K
authors.lastname: Tse
authors.forename: Jacqueline E
authors.initials: JE
authors.lastname: Schein
authors.forename: Michael
authors.initials: M
authors.lastname: Rivera
authors.forename: Brian M
authors.initials: BM
authors.lastname: Necela
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Kachergus
authors.forename: John D
authors.initials: JD
authors.lastname: Casler
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Mungall
authors.forename: Richard A
authors.initials: RA
authors.lastname: Moore
authors.forename: Marco A
authors.initials: MA
authors.lastname: Marra
authors.forename: John A
authors.initials: JA
authors.lastname: Copland
authors.forename: E Aubrey
authors.initials: EA
authors.lastname: Thompson
authors.forename: Robert C
authors.initials: RC
authors.lastname: Smallridge
authors.forename: Steven J M
authors.initials: SJ
authors.lastname: Jones
mesh_terms: D018249:Adenoma, Oxyphilic; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D018628:Gene Dosage; D006801:Humans; D008207:Lymphatic Metastasis; D016555:Matched-Pair Analysis; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D013961:Thyroid Gland / Q000473:pathology; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins