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Cancer Cell. 2018 Aug 13;34(2):256-270.e5. doi: 10.1016/j.ccell.2018.07.002.

Integrated Genomic Analysis of Hürthle Cell Cancer Reveals Oncogenic Drivers, Recurrent Mitochondrial Mutations, and Unique Chromosomal Landscapes.

Author information

1
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Surgery, Head and Neck Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: ganlyi@mskcc.org.
2
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
3
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
4
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
5
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
6
Molecular Cytogenetics Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
7
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Surgery, Head and Neck Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
8
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
9
Department of Surgery, Division of Endocrine Surgery, New York University Langone Medical Center, New York, NY, USA.
10
Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
11
Endocrine Oncology Branch, National Cancer Institute, Bethesda, MD, USA.
12
Department of Medicine, Head and Neck Medical Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
13
Department of Pathology, Head and Neck Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
14
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: chant@mskcc.org.

Abstract

The molecular foundations of Hürthle cell carcinoma (HCC) are poorly understood. Here we describe a comprehensive genomic characterization of 56 primary HCC tumors that span the spectrum of tumor behavior. We elucidate the mutational profile and driver mutations and show that these tumors exhibit a wide range of recurrent mutations. Notably, we report a high number of disruptive mutations to both protein-coding and tRNA-encoding regions of the mitochondrial genome. We reveal unique chromosomal landscapes that involve whole-chromosomal duplications of chromosomes 5 and 7 and widespread loss of heterozygosity arising from haploidization and copy-number-neutral uniparental disomy. We also identify fusion genes and disrupted signaling pathways that may drive disease pathogenesis.

KEYWORDS:

Hurthle cell carcinoma; copy-number alterations; fusion genes; genomics; mitochondrial mutations; transcriptome

PMID:
30107176
PMCID:
PMC6247912
[Available on 2019-08-13]
DOI:
10.1016/j.ccell.2018.07.002

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