Genomic Dissection of Hurthle Cell Carcinoma Reveals a Unique Class of Thyroid Malignancy

DOI PDF 被引用文献4件
  • Ian Ganly
    Human Oncology and Pathogenesis Program (I.G., J.R.F., S.E., L.G.T.M., Y.L., N.S., K.K., J.A.F., T.A.C.), New York, New York 10065;
  • Julio Ricarte Filho
    Human Oncology and Pathogenesis Program (I.G., J.R.F., S.E., L.G.T.M., Y.L., N.S., K.K., J.A.F., T.A.C.), New York, New York 10065;
  • Stephanie Eng
    Human Oncology and Pathogenesis Program (I.G., J.R.F., S.E., L.G.T.M., Y.L., N.S., K.K., J.A.F., T.A.C.), New York, New York 10065;
  • Ronald Ghossein
    Pathology (R.G.), New York, New York 10065;
  • Luc G. T. Morris
    Human Oncology and Pathogenesis Program (I.G., J.R.F., S.E., L.G.T.M., Y.L., N.S., K.K., J.A.F., T.A.C.), New York, New York 10065;
  • Yupu Liang
    Human Oncology and Pathogenesis Program (I.G., J.R.F., S.E., L.G.T.M., Y.L., N.S., K.K., J.A.F., T.A.C.), New York, New York 10065;
  • Nicholas Socci
    Human Oncology and Pathogenesis Program (I.G., J.R.F., S.E., L.G.T.M., Y.L., N.S., K.K., J.A.F., T.A.C.), New York, New York 10065;
  • Kasthuri Kannan
    Human Oncology and Pathogenesis Program (I.G., J.R.F., S.E., L.G.T.M., Y.L., N.S., K.K., J.A.F., T.A.C.), New York, New York 10065;
  • Qianxing Mo
    Department of Medicine and Dan L. Duncan Cancer Center (Q.M.), Baylor College of Medicine, Houston, Texas 77030
  • James A. Fagin
    Medicine (J.A.F.), Memorial Sloan-Kettering Cancer Center, New York, New York 10065;
  • Timothy A. Chan
    Departments of Radiation Oncology (T.A.C.), New York, New York 10065;

説明

<jats:sec><jats:title>Context:</jats:title><jats:p>Hurthle cell cancer (HCC) is an understudied cancer with poor prognosis.</jats:p></jats:sec><jats:sec><jats:title>Objective:</jats:title><jats:p>Our objective was to elucidate the genomic foundations of HCC.</jats:p></jats:sec><jats:sec><jats:title>Design and Setting:</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Conclusions:</jats:title><jats:p>Our data provide evidence that HCC may be a unique thyroid cancer distinct from papillary and follicular thyroid cancer.</jats:p></jats:sec>

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