Department of Clinical Oncology, Hospital Sirio Libanes, São Paulo, Brazil.
Foundation Medicine, Cambridge, Massachusetts, USA.
Oncologist. 2021 Apr;26(4):e715-e718. doi: 10.1002/onco.13694. Epub 2021 Feb 9.
The cyclin pathway may confer resistance to standard treatments but also offer novel therapeutic opportunities in prostate cancer. Herein, we analyzed prostate cancer samples (majority metastatic) using comprehensive genomic profiling performed by next-generation sequencing (315 genes, >500× coverage) for alterations in activating and sensitizing cyclin genes (CDK4 amplification, CDK6 amplification, CCND1, CCND2, CCND3, CDKN2B [loss], CDKN2A [loss], SMARCB1), androgen receptor (AR) gene, and coalterations in genes leading to cyclin inhibitor therapeutic resistance (RB1 and CCNE1). Overall, cyclin sensitizing pathway genomic abnormalities were found in 9.7% of the 5,356 tumors. Frequent alterations included CCND1 amplification (4.2%) and CDKN2A and B loss (2.4% each). Alterations in possible resistance genes, RB1 and CCNE1, were detected in 9.7% (up to 54.6% in neuroendocrine) and 1.2% of cases, respectively, whereas AR alterations were seen in 20.9% of tumors (~27.3% in anaplastic). Cyclin sensitizing alterations were also more frequently associated with concomitant AR alterations.
细胞周期通路可能导致对标准治疗产生耐药性，但也为前列腺癌提供了新的治疗机会。在此，我们使用下一代测序进行的全面基因组分析（315 个基因，>500×覆盖）分析了前列腺癌样本（多数为转移性），以检测激活和敏化细胞周期基因（CDK4 扩增、CDK6 扩增、CCND1、CCND2、CCND3、CDKN2B[缺失]、CDKN2A[缺失]、SMARCB1）、雄激素受体（AR）基因和导致细胞周期抑制剂治疗耐药的基因共突变（RB1 和 CCNE1）的改变。总的来说，在 5356 个肿瘤中发现了 9.7%的细胞周期敏化通路基因组异常。常见的改变包括 CCND1 扩增（4.2%）和 CDKN2A 和 B 缺失（各 2.4%）。可能导致耐药的基因 RB1 和 CCNE1 的改变分别在 9.7%（在神经内分泌肿瘤中高达 54.6%）和 1.2%的病例中检测到，而 AR 改变在 20.9%的肿瘤中可见（在间变性肿瘤中约为 27.3%）。细胞周期敏化改变也更常与同时存在的 AR 改变相关。
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