Margolis Benjamin, Dao Fanny, Licciardi Michael, Misirlioglu Selim, Olvera Narciso, Ramaswami Sitharam, Levine Douglas A
Laura and Isaac Perlmutter Comprehensive Cancer Center, NYU Langone Health, 550 1st Avenue, New York, NY 10016, USA.
Genome Technology Center, NYU Langone Health, 550 First Avenue, New York, NY 10016, USA.
Gynecol Oncol Rep. 2021 Aug 21;37:100850. doi: 10.1016/j.gore.2021.100850. eCollection 2021 Aug.
We sought to characterize the variability of amplification among metastatic sites of amplified high grade serous carcinoma (HGSC) cases to investigate the feasibility of targeting this alteration for therapeutic purposes.
Patients with amplified HGSC who underwent surgical cytoreduction with metastatic sites were identified from institutional molecular profiling reports and a population of HGSC cases screened using digital droplet PCR (ddPCR). Cases with normal copy number were included as controls. Slides from metastatic sites were cut from formalin-fixed paraffin-embedded tissue blocks, dissected for tumor of > 50% purity, and underwent DNA extraction. copy number was determined by ddPCR. Tumor purity was confirmed with mutant allele fraction from targeted massively parallel sequencing.
Four of 15 patients from an institutional database screened by ddPCR were found to have amplification. Three additional patients were identified from a query of institutional commercial clinical reports. Among these 7 amplified cases (2 uterine, 5 ovarian), 5 showed preservation of amplification (copy number > 5) among all metastatic sites. The remaining 2 cases had multiple metastatic sites without preserved amplification. Non-amplified cases had predominantly normal copy number across metastatic sites.
amplification is an early genomic event in HGSC and is preserved in most metastatic sites suggesting a uniform response to pathway targeting therapies.
我们试图描述高级别浆液性癌（HGSC）病例转移部位间扩增的变异性，以研究针对这种改变进行靶向治疗的可行性。
从机构分子谱分析报告以及使用数字液滴PCR（ddPCR）筛选的HGSC病例群体中，识别出接受过有转移部位的手术细胞减灭术的扩增HGSC患者。将拷贝数正常的病例作为对照。从福尔马林固定石蜡包埋组织块中切取转移部位的切片，解剖出纯度>50%的肿瘤组织，并进行DNA提取。通过ddPCR测定拷贝数。用靶向大规模平行测序的突变等位基因分数确认肿瘤纯度。
通过ddPCR筛选机构数据库中的15例患者，发现4例有扩增。通过查询机构商业临床报告又识别出另外3例患者。在这7例扩增病例（2例子宫，5例卵巢）中，5例在所有转移部位均显示扩增保留（拷贝数>5）。其余2例有多个转移部位但扩增未保留。非扩增病例在转移部位主要具有正常的拷贝数。
扩增是HGSC中的一个早期基因组事件，并且在大多数转移部位保留，提示对通路靶向治疗有一致反应。
