Association Between Preanalytical Factors and Tumor Mutational Burden Estimated by Next-Generation Sequencing-Based Multiplex Gene Panel Assay

被引：9

作者：

Quy, Pham Nguyen ^{[1
]}

Kanai, Masashi ^{[1
]}

Fukuyama, Keita ^{[5
]}

Kou, Tadayuki ^{[1
]}

Kondo, Tomohiro ^{[1
]}

Yamamoto, Yoshihiro ^{[1
]}

Matsubara, Junichi ^{[1
]}

Hiroshima, Akinori ^{[6
]}

Mochizuki, Hiroaki ^{[6
]}

Sakuma, Tomohiro ^{[6
]}

Kamada, Mayumi ^{[2
]}

Nakatsui, Masahiko ^{[2
]}

Eso, Yuji ^{[3
]}

Seno, Hiroshi ^{[3
]}

Masui, Toshihiko ^{[5
]}

Takaori, Kyoichi ^{[5
]}

Minamiguchi, Sachiko ^{[4
]}

Matsumoto, Shigemi ^{[1
]}

Muto, Manabu ^{[1
]}

机构：

[1] Kyoto Univ, Grad Sch Med, Dept Med Oncol, Kyoto, Japan

[2] Kyoto Univ, Grad Sch Med, Dept Biomed Data Intelligence, Kyoto, Japan

[3] Kyoto Univ, Grad Sch Med, Dept Gastroenterol & Hepatol, Kyoto, Japan

[4] Kyoto Univ, Grad Sch Med, Dept Diagnost Pathol, Kyoto, Japan

[5] Kyoto Univ, Grad Sch Med, Div Hepatobiliary Pancreat Surg & Transplantat, Dept Surg, Kyoto, Japan

[6] Mitsui Knowledge Ind Co Ltd, Biomed Dept, Tokyo, Japan

来源：

ONCOLOGIST | 2019年 / 24卷 / 12期

基金：

日本学术振兴会;

关键词：

Mutational burden; Next‐ generation sequencing; DNA quality; Immune checkpoint inhibitors;

D O I：

10.1634/theoncologist.2018-0587

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background Tumor mutational burden (TMB) measured via next-generation sequencing (NGS)-based gene panel is a promising biomarker for response to immune checkpoint inhibitors (ICIs) in solid tumors. However, little is known about the preanalytical factors that can affect the TMB score. Materials and Methods Data of 199 patients with solid tumors who underwent multiplex NGS gene panel (OncoPrime), which was commercially provided by a Clinical Laboratory Improvement Amendments-licensed laboratory and covered 0.78 megabase (Mb) of capture size relevant to the TMB calculation, were reviewed. Associations between the TMB score and preanalytical factors, including sample DNA quality, sample type, sampling site, and storage period, were analyzed. Clinical outcomes of patients with a high TMB score (>= 10 mutations per megabase) who received anti-programmed cell death protein 1 antibodies (n = 22) were also analyzed. Results Low DNA library concentration (<5 nM), formalin-fixed paraffin-embedded tissue (FFPE), and the prolonged sample storage period (range, 0.9-58.1 months) correlated with a higher TMB score. After excluding low DNA library samples from the analysis, FFPE samples, but not the sample storage period, exhibited a marked correlation with a high TMB score. Of 22 patients with a high TMB score, we observed the partial response in 2 patients (9.1%). Conclusion Our results indicate that the TMB score estimated via NGS-based gene panel could be affected by the DNA library concentration and sample type. These factors could potentially increase the false-positive and/or artifactual variant calls. As each gene panel has its own pipeline for variant calling, it is unknown whether these factors have a significant effect in other platforms. Implications for Practice A high tumor mutational burden score, as estimated via next-generation sequencing-based gene panel testing, should be carefully interpreted as it could be affected by the DNA library concentration and sample type.

引用

页码：E1401 / E1408

页数：8

共 42 条

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