Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, United States.
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, United States.
Elife. 2018 Sep 4;7:e37294. doi: 10.7554/eLife.37294.
The level of copy number alteration (CNA), termed CNA burden, in the tumor genome is associated with recurrence of primary prostate cancer. Whether CNA burden is associated with prostate cancer survival or outcomes in other cancers is unknown. We analyzed the CNA landscape of conservatively treated prostate cancer in a biopsy and transurethral resection cohort, reflecting an increasingly common treatment approach. We find that CNA burden is prognostic for cancer-specific death, independent of standard clinical prognosticators. More broadly, we find CNA burden is significantly associated with disease-free and overall survival in primary breast, endometrial, renal clear cell, thyroid, and colorectal cancer in TCGA cohorts. To assess clinical applicability, we validated these findings in an independent pan-cancer cohort of patients whose tumors were sequenced using a clinically-certified next generation sequencing assay (MSK-IMPACT), where prognostic value varied based on cancer type. This prognostic association was affected by incorporating tumor purity in some cohorts. Overall, CNA burden of primary and metastatic tumors is a prognostic factor, potentially modulated by sample purity and measurable by current clinical sequencing.
肿瘤基因组中的拷贝数改变（CNA）水平，称为 CNA 负担，与原发性前列腺癌的复发有关。CNA 负担是否与其他癌症的前列腺癌生存或结局有关尚不清楚。我们分析了活检和经尿道前列腺切除术队列中保守治疗的前列腺癌的 CNA 图谱，反映了一种越来越常见的治疗方法。我们发现 CNA 负担与癌症特异性死亡相关，独立于标准临床预后因素。更广泛地说，我们发现 CNA 负担与 TCGA 队列中原发性乳腺癌、子宫内膜癌、肾透明细胞癌、甲状腺癌和结直肠癌的无病生存和总生存显著相关。为了评估临床适用性，我们在一个独立的泛癌患者队列中验证了这些发现，这些患者的肿瘤使用经过临床认证的下一代测序检测（MSK-IMPACT）进行了测序，其中预后价值因癌症类型而异。这种预后相关性受到某些队列中肿瘤纯度的影响。总体而言，原发和转移肿瘤的 CNA 负担是一个预后因素，可能受到样本纯度的调节，并且可以通过当前的临床测序来衡量。
