Implementing tumor mutational burden (TMB) analysis in routine diagnostics-a primer for molecular pathologists and clinicians

被引：152

作者：

Allgaeuer, Michael ^{[1
]}

Budczies, Jan ^{[1
,2
,3
]}

Christopoulos, Petros ^{[4
,5
,6
]}

Endris, Volker ^{[1
]}

Lier, Amelie ^{[1
]}

Rempel, Eugen ^{[1
]}

Volckmar, Anna-Lena ^{[1
]}

Kirchner, Martina ^{[1
]}

von Winterfeld, Moritz ^{[1
]}

Leichsenring, Jonas ^{[1
]}

Neumann, Olaf ^{[1
]}

Froehling, Stefan ^{[3
,7
]}

Penzel, Roland ^{[1
]}

Thomas, Michael ^{[4
,5
,6
]}

Schirmacher, Peter ^{[1
,2
,3
]}

Stenzinger, Albrecht ^{[1
,2
,3
]}

机构：

[1] Univ Hosp Heidelberg, Inst Pathol, Neuenheimer Feld 224, D-69120 Heidelberg, Germany

[2] German Canc Consortium DKTK, Partner Site Heidelberg, Heidelberg, Germany

[3] German Canc Res Ctr, Heidelberg, Germany

[4] Heidelberg Univ Hosp, Thoraxklin, Dept Thorac Oncol, Heidelberg, Germany

[5] TLRC H, Heidelberg, Germany

[6] German Ctr Lung Res DZL, Giessen, Germany

[7] Natl Ctr Tumor Dis NCT, Dept Translat Oncol, Heidelberg, Germany

来源：

TRANSLATIONAL LUNG CANCER RESEARCH | 2018年 / 7卷 / 06期

关键词：

Tumor mutational burden (TMB); mutational load; panel; next-generation sequencing (NGS); sequencing; METASTATIC UROTHELIAL CARCINOMA; PD-1; BLOCKADE; LUNG-CANCER; T-CELL; OPEN-LABEL; INFILTRATING LYMPHOCYTES; CHECKPOINT BLOCKADE; CTLA-4; NEOANTIGEN LOAD; SINGLE-ARM;

D O I：

10.21037/tlcr.2018.08.14

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Tumor mutational burden (TMB) is a new biomarker for prediction of response to PD-(L) 1 treatment. Comprehensive sequencing approaches (i. e., whole exome and whole genome sequencing) are ideally suited to measure TMB directly. However, as their applicability in routine diagnostics is currently limited by high costs, long turnaround times and poor availability of fresh tissue, targeted next-generation sequencing (NGS) of formalin-fixed and paraffin-embedded (FFPE) samples appears to be a more feasible and straight-forward approach for TMB approximation, which can be seamlessly integrated in already existing diagnostic workflows and pipelines. In this work, we provide an overview of the clinical implications of TMB testing and highlight key parameters including pre-analysis, analysis and post-analytical steps that influence and shape TMB approximation by panel sequencing. Collectively, the data will not only serve as a field guide and state of the art knowledge source for molecular pathologists who consider implementation of TMB measurement in their lab, but also enable clinicians in understanding the specific parameters influencing TMB test results and reporting.

引用

页码：703 / 715

页数：13