细胞学样本的肿瘤突变负担：一项初步研究。

Tumor mutational burden on cytological samples: A pilot study.

机构信息

Department of Public Health, University Federico II of Naples, Naples, Italy.

Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.

出版信息

Cancer Cytopathol. 2021 Jun;129(6):460-467. doi: 10.1002/cncy.22400. Epub 2020 Dec 30.

DOI:10.1002/cncy.22400

PMID:33378102

Abstract

BACKGROUND

Immune-checkpoint inhibitors (ICIs) represent an important treatment option for patients who have advanced stage non-small cell lung cancer (NSCLC). Currently, evaluation of the expression level of programmed death-ligand 1 (PD-L1) has proven highly successful as a positive predictive biomarker for ICIs. In addition to PD-L1, other promising predictive biomarkers are emerging, including high tumor mutational burden (TMB-H). However, measuring TMB-H remains challenging for several reasons, among which is the difficulty in obtaining adequate tissue material from NSCLC patients. There are no data in the current literature regarding the possibility of adopting cell blocks (CBs) for TMB evaluation; therefore, our goal was to evaluate the feasibility of analyzing TMB on CBs.

METHODS

For evaluation of differences in run metric parameters, 8 pairs of histological and CB samples from patients with NSCLC were analyzed using the Oncomine Tumor Mutational Load Assay on Ion Torrent S5 GS next-generation sequencing (NGS) platform.

RESULTS

Most CBs (6/8, 75.0%) were successfully analyzed by adopting the broad NGS panel approach. CBs provided results similar to those obtained on histological matched specimens in terms of median total reads (7207048.80 vs 7558817.80), median mapped reads (7075753.83 vs 7513822.00), median read lengths (115.50 vs. 113.00), median percentage of reads on-target (97.49% vs. 98.45%), median average reads per amplicon (454.67 vs 476.14), and median uniformity of amplicon coverage (83.52% vs 84.13%).

CONCLUSION

In this pilot study, we demonstrated the technical feasibility of assessing TMB on CBs.

摘要

背景

免疫检查点抑制剂（ICIs）是治疗晚期非小细胞肺癌（NSCLC）患者的重要选择。目前，程序性死亡配体 1（PD-L1）的表达水平已被证明是 ICIs 的一个有价值的阳性预测生物标志物。除了 PD-L1 之外，其他有前途的预测生物标志物也在不断涌现，包括高肿瘤突变负荷（TMB-H）。然而，由于多种原因，测量 TMB-H 仍然具有挑战性，其中包括从 NSCLC 患者中获得足够组织材料的困难。目前的文献中没有关于采用细胞块（CB）进行 TMB 评估的可能性的数据；因此，我们的目标是评估分析 CB 上的 TMB 的可行性。

方法

为了评估运行指标参数的差异，我们使用 Ion Torrent S5 GS 下一代测序（NGS）平台上的 Oncomine Tumor Mutational Load 检测对 8 对 NSCLC 患者的组织学和 CB 样本进行了分析。

结果

采用广泛的 NGS 面板方法，成功分析了 6/8（75.0%）的 CB。在中位数总读取数（7207048.80 对 7558817.80）、中位数映射读取数（7075753.83 对 7513822.00）、中位数读取长度（115.50 对 113.00）、中位数目标读取百分比（97.49% 对 98.45%）、中位数每个扩增子的平均读取数（454.67 对 476.14）和中位数扩增子覆盖均匀度（83.52% 对 84.13%）方面，CB 提供的结果与组织学匹配标本相似。