Biallelic Inactivation of BRCA2 in Platinum-sensitive Metastatic Castration-resistant Prostate Cancer.
Biallelic Inactivation of BRCA2 in Platinum-sensitive Metastatic Castration-resistant Prostate Cancer.
复制标题
铂敏感转移性去势抵抗性前列腺癌中 BRCA2 的双等位基因失活。
DOI：
10.1016/j.eururo.2015.11.022
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发表时间：
2016-06
期刊：
影响因子：
23.4
通讯作者：
Montgomery B
中科院分区：
文献类型：
--
作者：
Cheng HH;Pritchard CC;Boyd T;Nelson PS;Montgomery B
了解特异性治疗敏感性的分子基础将推进前列腺癌精准医学的目标。我们确定了3例转移性去势抵抗性前列腺癌患者，尽管在先前的标准治疗中疾病进展，但他们对铂化疗（不是前列腺癌的一线治疗）取得了特殊的反应。通过对原发性和转移性肿瘤的靶向下一代测序，我们发现所有三名患者都有BRCA2双等位基因失活，BRCA2是一种对同源DNA修复至关重要的肿瘤抑制基因。值得注意的是，其中两人有种系BRCA2突变，包括一名没有引人注目的家族史的患者，他在66岁时被诊断出来。第三名患者有体细胞BRCA2纯合拷贝丢失。转移性去势抵抗性前列腺癌的双等位基因BRCA2失活值得进一步探索，作为对铂化疗敏感性的预测性生物标志物。
Understanding the molecular underpinnings of sensitivity to specific therapies will advance the goal of precision medicine in prostate cancer. We identified three patients with metastatic, castration resistant prostate cancer who achieved exceptional response to platinum chemotherapy (not frontline treatment for prostate cancer), despite disease progression on prior standard therapies. Using targeted next generation sequencing on primary and metastatic tumor, we found that all three patients had biallelic inactivation of BRCA2, a tumor suppressor gene critical for homologous DNA repair. Notably, two had germline BRCA2 mutations, including a patient without compelling family history who was diagnosed at age 66. The third patient had somatic BRCA2 homozygous copy loss. Biallelic BRCA2 inactivation in metastatic castration resistant prostate cancer warrants further exploration as a predictive biomarker for sensitivity to platinum chemotherapy.