A comprehensive assessment of a newly designed non-exonic SNP-based NGS panel for HRD detection

Ovarian cancer is a global problem, is typically diagnosed at a late stage and has no effective screening strategy. Platinum-based chemotherapy or Poly(ADP-ribose) polymerase inhibitors (PARPis) treatment are most frequently applied for ovarian cancer patients who are inoperable and in the advanced stage. The recognition of homologous recombination deficiency (HRD) as a biomarker to predict the effect of Platinum-based or PARPis treatment. WGS and WES can detect tumor HRD status but have several disadvantages which restrict their clinical application. My choice HRD CDx and Foundation Focus CDx are approved by FDA for HRD detection, however, whether they are applicable to the Chinese population or not is unknown. In this study, we created an SNP-based Tg-NGS panel to fill in gaps in Chinese patients’ HRD screening. Our results showed that the panel is cost and time-saving compared with WGS, but equivalent with SNP microarray on CNV and HRD detection. In summary, this newly developed kit is promising in clinical application to guide ovarian cancer and even other cancer types therapy. 27 Ovarian cancer samples were tested by OncoScan® CNV FFPE Arrays to detect whole genome copy number variation.

卵巢癌是全球性公共健康难题，通常于晚期确诊，且尚无有效的临床筛查策略。对于不可手术的晚期卵巢癌患者，铂类化疗或聚腺苷二磷酸核糖聚合酶抑制剂（PARP抑制剂，PARPis）是最常用的治疗方案。同源重组缺陷（homologous recombination deficiency, HRD）作为一类生物标志物，可用于预测铂类化疗或PARP抑制剂的治疗响应效果。全基因组测序（whole genome sequencing, WGS）与全外显子测序（whole exome sequencing, WES）可检测肿瘤HRD状态，但存在诸多局限性，限制了其临床转化应用。本研究选用的HRD CDx与Foundation Focus CDx两款试剂盒均已获美国食品药品监督管理局（FDA）批准用于HRD检测，但二者是否适用于中国人群仍不明确。本研究开发了一款基于单核苷酸多态性（single nucleotide polymorphism, SNP）的Tg-NGS测序panel，以填补中国卵巢癌患者HRD筛查领域的空白。研究结果显示，相较于WGS，该检测方法成本更低、耗时更短；在拷贝数变异（copy number variation, CNV）与HRD检测性能上，则与SNP芯片相当。综上，这款新开发的检测试剂盒在指导卵巢癌乃至其他癌种的临床治疗方面具有良好的应用前景。本研究采用OncoScan® CNV福尔马林固定石蜡包埋（FFPE）组织阵列对27例卵巢癌样本进行了全基因组拷贝变异检测。