Widespread Chromosomal Losses and Mitochondrial DNA Alterations as Genetic Drivers in Hürthle Cell Carcinoma.

Autor:	Gopal RK; Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA; Harvard Medical School, Boston, MA 02115, USA., Kübler K; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA., Calvo SE; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA., Polak P; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA., Livitz D; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Rosebrock D; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Sadow PM; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA., Campbell B; Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA., Donovan SE; Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA., Amin S; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA., Gigliotti BJ; Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA., Grabarek Z; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA., Hess JM; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Stewart C; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Braunstein LZ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Arndt PF; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Mordecai S; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA., Shih AR; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA., Chaves F; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA., Zhan T; Institute for Technology Assessment, Massachusetts General Hospital, Boston, MA 02114, USA., Lubitz CC; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA; Institute for Technology Assessment, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA., Kim J; Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Iafrate AJ; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA., Wirth L; Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA., Parangi S; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA., Leshchiner I; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Daniels GH; Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Thyroid Unit, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA., Mootha VK; Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA., Dias-Santagata D; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA., Getz G; Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA. Electronic address: gadgetz@broadinstitute.org., McFadden DG; Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Thyroid Unit, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Internal Medicine, Division of Endocrinology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: david.mcfadden@utsouthwestern.edu.
Jazyk:	angličtina
Zdroj:	Cancer cell [Cancer Cell] 2018 Aug 13; Vol. 34 (2), pp. 242-255.e5.
DOI:	10.1016/j.ccell.2018.06.013
Abstrakt:	Hürthle cell carcinoma of the thyroid (HCC) is a form of thyroid cancer recalcitrant to radioiodine therapy that exhibits an accumulation of mitochondria. We performed whole-exome sequencing on a cohort of primary, recurrent, and metastatic tumors, and identified recurrent mutations in DAXX, TP53, NRAS, NF1, CDKN1A, ARHGAP35, and the TERT promoter. Parallel analysis of mtDNA revealed recurrent homoplasmic mutations in subunits of complex I of the electron transport chain. Analysis of DNA copy-number alterations uncovered widespread loss of chromosomes culminating in near-haploid chromosomal content in a large fraction of HCC, which was maintained during metastatic spread. This work uncovers a distinct molecular origin of HCC compared with other thyroid malignancies. (Copyright © 2018 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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