title: Genomic dissection of Hurthle cell carcinoma reveals a unique class of thyroid malignancy.
abstract: BACKGROUND
  Hurthle cell cancer (HCC) is an understudied cancer with poor prognosis.
  
  
  OBJECTIVE
  Our objective was to elucidate the genomic foundations of HCC.
  
  
  METHODS
  We conducted a large-scale integrated analysis of mutations, gene expression profiles, and copy number alterations in HCC at a single tertiary-care cancer institution.
  
  
  METHODS
  Mass spectrometry-based genotyping was used to interrogate hot spot point mutations in the most common thyroid oncogenes: BRAF, RET, NRAS, HRAS, KRAS, PIK3CA, MAP2K1, and AKT1. In addition, common oncogenic fusions of RET and NTRK1 as well as PAX8/PPARγ and AKAP9-BRAF were also assessed by RT-PCR. Global copy number changes and gene expression profiles were determined in the same tumor set as the mutational analyses.
  
  
  RESULTS
  We report that the mutational, transcriptional, and copy number profiles of HCC were distinct from those of papillary thyroid cancer and follicular thyroid cancer, indicating HCC to be a unique type of thyroid malignancy. Unsupervised hierarchical clustering of gene expression showed the 3 groups of Hurthle tumors (Hurthle cell adenoma [HA], minimally invasive Hurthle cell carcinoma [HMIN], and widely invasive Hurthle cell carcinoma [HWIDE] clustered separately with a marked difference between HWIDE and HA. Global copy number analysis also indicated distinct subgroups of tumors that may arise as HWIDE and HMIN. Molecular pathways that differentiate HA from HWIDE included the PIK3CA-Akt-mTOR and Wnt/β-catenin pathways, potentially providing a rationale for new targets for this type of malignancy.
  
  
  CONCLUSIONS
  Our data provide evidence that HCC may be a unique thyroid cancer distinct from papillary and follicular thyroid cancer.
authors.affiliation: Memorial Sloan Kettering Cancer Center-Human Oncology and Pathogenesis Program, 1275 York Avenue, New York, New York 10065, USA.
authors.forename: Ian
authors.initials: I
authors.lastname: Ganly
authors.forename: Julio
authors.initials: J
authors.lastname: Ricarte Filho
authors.forename: Stephanie
authors.initials: S
authors.lastname: Eng
authors.forename: Ronald
authors.initials: R
authors.lastname: Ghossein
authors.forename: Luc G T
authors.initials: LG
authors.lastname: Morris
authors.forename: Yupu
authors.initials: Y
authors.lastname: Liang
authors.forename: Nicholas
authors.initials: N
authors.lastname: Socci
authors.forename: Kasthuri
authors.initials: K
authors.lastname: Kannan
authors.forename: Qianxing
authors.initials: Q
authors.lastname: Mo
authors.forename: James A
authors.initials: JA
authors.lastname: Fagin
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Chan
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D018249:Adenoma, Oxyphilic; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002173:Cancer Care Facilities; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D056915:DNA Copy Number Variations; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009519:New York City; D017354:Point Mutation; D062606:Tertiary Care Centers; D013961:Thyroid Gland / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000601:surgery
chemical_list: D009363:Neoplasm Proteins
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