Li Zhongjun, Hao Ping, Wu Qingjian, Li Fengjie, Zhao Jiang, Wu Kaijin, Qu Cunye, Chen Yibu, Li Meng, Chen Xuelian, Stucky Andres, Zhong Jiangjian, Li Longkun, Zhong Jiang F
Department of Blood Transfusion, Second Affiliated Hospital, Third Military Medical University, Chongqing, P. R. China.
Ostrow School of Dentistry and Department of Pediatrics, School of Medicine, University of Southern California, Los Angeles, CA, USA.
Oncotarget. 2016 Mar 29;7(13):16172-9. doi: 10.18632/oncotarget.7473.
Metastasis is the major cause of death among cancer patients, yet early detection and intervention of metastasis could significantly improve their clinical outcomes. We have sequenced and analyzed RNA (Expression) and DNA (Mutations) from the primary tumor (PT), tumor extension (TE) and lymphatic metastatic (LM) sites of patients with clear cell renal cell carcinoma (CCRCC) before treatment. Here, we report a three-nucleotide deletion near the C-region of Plk5 that is specifically associated with the lymphatic metastasis. This mutation is un-detectable in the PT, becomes detectable in the TE and dominates the LM tissue. So while only a few primary cancer cells carry this mutation, the majority of metastatic cells have this mutation. The increasing frequency of this mutation in metastatic tissue suggests that this Plk5 deletion could be used as an early indicator of CCRCC metastasis, and be identified by low cost PCR assay. A large scale clinical trial could reveal whether a simple PCR assay for this mutation at the time of nephrectomy could identify and stratify high-risk CCRCC patients for treatments.
转移是癌症患者死亡的主要原因，然而转移的早期检测和干预可显著改善其临床结局。我们对接受治疗前的透明细胞肾细胞癌（CCRCC）患者的原发性肿瘤（PT）、肿瘤扩展（TE）和淋巴转移（LM）部位的RNA（表达）和DNA（突变）进行了测序和分析。在此，我们报告了Plk5基因C区域附近的一个三核苷酸缺失，该缺失与淋巴转移特异性相关。此突变在原发性肿瘤中无法检测到，在肿瘤扩展部位可检测到，并在淋巴转移组织中占主导。因此，虽然只有少数原发性癌细胞携带此突变，但大多数转移细胞都有此突变。该突变在转移组织中的频率增加表明，这种Plk5缺失可作为CCRCC转移的早期指标，并可通过低成本的PCR检测法进行识别。大规模临床试验可能会揭示，在肾切除时针对该突变进行简单的PCR检测是否能够识别高危CCRCC患者并对其进行分层治疗。
