Kanda Mitsuro, Terashima Masanori, Kinoshita Takahiro, Yabusaki Hiroshi, Tokunaga Masanori, Kodera Yasuhiro
Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showa-Ku, Nagoya, 466-8550, Japan.
Department of Gastric Surgery, Shizuoka Cancer Center, Shizuoka, Japan.
Gastric Cancer. 2023 Jan;26(1):108-115. doi: 10.1007/s10120-022-01351-4. Epub 2022 Nov 11.
Formalin-fixed, paraffin-embedded (FFPE) samples acquired and preserved adequately are expected to faithfully maintain tumor characteristics. Endoscopic biopsy tissues represent an attractive resource for identifying predictive biomarkers to evaluate pretreatment responses of patients with advanced gastric cancer (GC). However, whether genomic profiles obtained through next-generation sequencing (NGS) using biopsy samples match well with those gained from surgical FFPE samples remains a concern.
We collected 50 FFPE samples (26 biopsies and 24 surgical samples) from patients with GC who participated in phase III clinical trial JCOG1509. The quality and quantity of FFPE samples were determined for deep sequencing using NGS. We queried a 435-gene panel CANCERPLEX-JP to generate comprehensive genomic profiling data including the tumor mutation burden (TMB).
The median DNA yields and NGS success rates of biopsy samples compared with surgical samples were 879 ng and 80.8% vs 8523 ng and 100%, respectively. Epstein-Barr virus and microsatellite instability-high were detected in 9.5% of biopsy samples. Comparing the genomic profiles of 18 paired samples for which NGS data were available, we detected identical somatic mutations in paired biopsy and surgical samples (kappa coefficient, 0.8692). TMB positively correlated between paired biopsy and surgical samples (correlation coefficient, 0.6911).
NGS is applicable to the analysis of FFPE samples of GC acquired by the endoscopic biopsy, and the data were highly concordant with those obtained from surgical specimens of the same patients.
获取并妥善保存的福尔马林固定石蜡包埋(FFPE)样本有望忠实地保留肿瘤特征。内镜活检组织是鉴定预测性生物标志物以评估晚期胃癌(GC)患者预处理反应的一个有吸引力的资源。然而,通过对活检样本进行二代测序(NGS)获得的基因组图谱与从手术FFPE样本获得的图谱是否良好匹配仍令人担忧。
我们从参与III期临床试验JCOG1509的GC患者中收集了50份FFPE样本(26份活检样本和24份手术样本)。测定FFPE样本的质量和数量,以便使用NGS进行深度测序。我们查询了一个包含435个基因的CANCERPLEX-JP基因panel,以生成包括肿瘤突变负荷(TMB)在内的全面基因组图谱数据。
与手术样本相比,活检样本的DNA产量中位数和NGS成功率分别为879 ng和80.8%,而手术样本分别为8523 ng和100%。在9.5%的活检样本中检测到爱泼斯坦-巴尔病毒和微卫星高度不稳定。比较18对可获得NGS数据的配对样本的基因组图谱,我们在配对的活检样本和手术样本中检测到相同的体细胞突变(kappa系数,0.8692)。配对的活检样本和手术样本之间TMB呈正相关(相关系数,0.6911)。
NGS适用于分析通过内镜活检获得的GC的FFPE样本,且数据与从同一患者的手术标本获得的数据高度一致。