Department of Urology, Qilu Hospital of Shandong University, 107 Jinan Culture Road, Jinan, 250012 Shandong, China.
Life Healthcare Medical Laboratory Co., Ltd., Hangzhou, 310052 Zhejiang, China.
Biomed Res Int. 2020 Sep 30;2020:2495157. doi: 10.1155/2020/2495157. eCollection 2020.
Clear cell renal cell carcinoma (ccRCC) accounts for more than 75% of renal cell carcinoma. Nearly 25% of ccRCC patients were diagnosed with metastasis. Though the genomic profile of ccRCC has been widely studied, the difference between localized and metastatic ccRCC was not clarified. Primary tumor samples and matched whole blood were collected from 106 sporadic patients diagnosed with renal clear cell carcinoma at Qilu Hospital of Shandong University from January 2017 to November 2019, and 17 of them were diagnosed with metastasis. A hybridization capture-based next-generation sequencing of 618 cancer-related genes was performed to investigate the somatic and germline variants, tumor mutation burden (TMB), and microsatellite instability (MSI). Five genes with significantly different prevalence were identified in the metastatic group, especially (17.65% vs. 0%) and (17.65% vs. 0%). The altered frequency of (0% vs. 27%) and (24% vs. 10%) differed between the metastatic and nonmetastatic groups, which may relate to the prognosis. Of these 106 patients, 42 patients (39.62%) had at least one alteration in DNA damage repair (DDR) genes, including 58.82% of metastatic ccRCC patients and 35.96% of ccRCC patients without metastasis. Ten pathogenic or likely pathogenic (P/LP) variants were identified in 11 sporadic clear cell renal cell carcinoma patients (10.38%), including rarely reported (n=1), (n=1), (n=1), (n=1), and (n=1). No significant difference in the ratio of P/LP variant carriers or TMB was identified between the metastatic and nonmetastatic groups. We found a unique genomic feature of Chinese metastatic ccRCC patients with a higher prevalence of alterations in DDR, , and Further investigated studies and drug development are needed in the future.
透明细胞肾细胞癌（ccRCC）占肾细胞癌的 75%以上。近 25%的 ccRCC 患者被诊断为转移。尽管 ccRCC 的基因组特征已被广泛研究，但局部和转移性 ccRCC 之间的差异尚未阐明。本研究从 2017 年 1 月至 2019 年 11 月，收集了山东大学齐鲁医院 106 例散发性肾透明细胞癌患者的原发性肿瘤组织样本和配对全血，其中 17 例患者被诊断为转移。采用杂交捕获二代测序对 618 个与癌症相关的基因进行检测，以研究体细胞和种系变异、肿瘤突变负荷（TMB）和微卫星不稳定性（MSI）。在转移性组中鉴定出 5 个具有显著不同流行率的基因，特别是 （17.65% vs. 0%）和 （17.65% vs. 0%）。（0% vs. 27%）和 （24% vs. 10%）在转移性和非转移性组之间的改变频率不同，这可能与预后有关。在这 106 名患者中，42 名（39.62%）至少有一个 DNA 损伤修复（DDR）基因的改变，其中 58.82%的转移性 ccRCC 患者和 35.96%的无转移 ccRCC 患者有改变。在 11 例散发性透明细胞肾细胞癌患者中发现了 10 个致病性或可能致病性（P/LP）变异（10.38%），包括罕见报道的 （n=1）、 （n=1）、 （n=1）、 （n=1）和 （n=1）。在转移性和非转移性组之间，P/LP 变异携带者或 TMB 的比例没有差异。我们发现了中国转移性 ccRCC 患者独特的基因组特征，其 DDR 、 和 基因的改变更为常见。未来需要进一步的研究和药物开发。
