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Updated: May 12, 2026

Establishment and Characterization of Patient-Derived Xenograft Models of Anaplastic Thyroid Carcinoma and Head and Neck Squamous Cell Carcinoma
Published on: June 2, 2023
Genomic dissection of Hurthle cell carcinoma reveals a unique class of thyroid malignancy
Ian Ganly1, Julio Ricarte Filho, Stephanie Eng
1Memorial Sloan Kettering Cancer Center-Human Oncology and Pathogenesis Program, 1275 York Avenue, New York, New York 10065, USA.
Context:
Hurthle cell cancer (HCC) is an understudied cancer with poor prognosis.
Objective:
Our objective was to elucidate the genomic foundations of HCC.
Design And Setting:
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.
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