Bratic Hench Ivana, Roma Luca, Conticelli Floriana, Bubendorf Lenard, Calgua Byron, Le Magnen Clémentine, Piscuoglio Salvatore, Rubin Mark A, Chirindel Alin, Nicolas Guillaume P, Vlajnic Tatjana, Zellweger Tobias, Templeton Arnoud J, Stenner Frank, Ruiz Christian, Rentsch Cyrill, Bubendorf Lukas
Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, 4031 Basel, Switzerland.
Department of Public Health, University of Naples Federico II, 80131 Naples, Italy.
Cancers (Basel). 2023 Dec 21;16(1):45. doi: 10.3390/cancers16010045.
Most men with prostate cancer (PCa), despite potentially curable localized disease at initial diagnosis, progress to metastatic disease. Despite numerous treatment options, choosing the optimal treatment for individual patients remains challenging. Biomarkers guiding treatment sequences in an advanced setting are lacking. To estimate the diagnostic potential of liquid biopsies in guiding personalized treatment of PCa, we evaluated the utility of a custom-targeted next-generation sequencing (NGS) panel based on the AmpliSeq HD Technology. Ultra-deep sequencing on plasma circulating free DNA (cfDNA) samples of 40 metastatic castration-resistant PCa (mCRPC) and 28 metastatic hormone-naive PCa (mCSPC) was performed. CfDNA somatic mutations were detected in 48/68 (71%) patients. Of those 68 patients, 42 had matched tumor and cfDNA samples. In 21/42 (50%) patients, mutations from the primary tumor tissue were detected in the plasma cfDNA. In 7/42 (17%) patients, mutations found in the primary tumor were not detected in the cfDNA. Mutations from primary tumors were detected in all tested mCRPC patients (17/17), but only in 4/11 with mCSPC. AR amplifications were detected in 12/39 (31%) mCRPC patients. These results indicate that our targeted NGS approach has high sensitivity and specificity for detecting clinically relevant mutations in PCa.
大多数前列腺癌（PCa）患者尽管在初诊时可能患有可治愈的局限性疾病，但仍会进展为转移性疾病。尽管有多种治疗选择，但为个体患者选择最佳治疗方案仍然具有挑战性。目前缺乏在晚期情况下指导治疗顺序的生物标志物。为了评估液体活检在指导PCa个性化治疗中的诊断潜力，我们评估了基于AmpliSeq HD技术的定制靶向新一代测序（NGS）面板的效用。对40例转移性去势抵抗性PCa（mCRPC）和28例转移性激素初治PCa（mCSPC）的血浆循环游离DNA（cfDNA）样本进行了超深度测序。在48/68（71%）的患者中检测到cfDNA体细胞突变。在这68例患者中，42例有匹配的肿瘤和cfDNA样本。在21/42（50%）的患者中，在血浆cfDNA中检测到来自原发肿瘤组织的突变。在7/42（17%）的患者中，在cfDNA中未检测到原发肿瘤中发现的突变。在所有测试的mCRPC患者（17/17）中均检测到原发肿瘤的突变，但在mCSPC患者中仅在4/11中检测到。在12/39（31%）的mCRPC患者中检测到AR扩增。这些结果表明，我们的靶向NGS方法在检测PCa临床相关突变方面具有高灵敏度和特异性。
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