广泛的染色体缺失和线粒体 DNA 改变作为 Hurthle 细胞癌的遗传驱动因素。
Widespread Chromosomal Losses and Mitochondrial DNA Alterations as Genetic Drivers in Hürthle Cell Carcinoma.
机构信息
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.
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.
出版信息
Cancer Cell. 2018 Aug 13;34(2):242-255.e5. doi: 10.1016/j.ccell.2018.06.013.
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.
甲状腺 Hurthle 细胞癌 (HCC) 是一种对放射性碘治疗具有抗性的甲状腺癌，其表现为线粒体的积累。我们对一组原发性、复发性和转移性肿瘤进行了全外显子组测序，发现了 DAXX、TP53、NRAS、NF1、CDKN1A、ARHGAP35 和 TERT 启动子的反复突变。对 mtDNA 的平行分析揭示了电子传递链复合物 I 亚基的反复同型突变。对 DNA 拷贝数改变的分析揭示了广泛的染色体丢失，最终导致 HCC 的大部分接近单倍体染色体含量，并且在转移扩散过程中得以维持。这项工作揭示了与其他甲状腺恶性肿瘤相比，HCC 的独特分子起源。
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