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.
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.
Cancer Cell. 2018 Aug 13;34(2):256-270.e5. doi: 10.1016/j.ccell.2018.07.002.
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.
Hürthle 细胞癌 (HCC) 的分子基础知之甚少。在这里，我们描述了对 56 例原发性 HCC 肿瘤的全面基因组特征分析，这些肿瘤涵盖了肿瘤行为的范围。我们阐明了突变特征和驱动突变，并表明这些肿瘤表现出广泛的复发性突变。值得注意的是，我们报告了大量对线粒体基因组的蛋白质编码和 tRNA 编码区域的破坏性突变。我们揭示了独特的染色体景观，包括染色体 5 和 7 的全染色体重复以及源于单倍体化和拷贝数中性单亲二体性的广泛杂合性丢失。我们还鉴定了可能导致疾病发病机制的融合基因和破坏的信号通路。
