Tumor Mutation Burden NGS Panel

Tumor Mutational Burden (TMB), defined as the number of somatic non-synonymous mutations per megabase (mut/Mb) of genomic sequence, reflects a tumor's potential to generate neoantigens and is closely associated with DNA repair deficiencies such as dMMR/MSI-H and POLE/POLD1 mutations. A high TMB (TMB-H) indicates greater immunogenicity and serves as a predictive biomarker for response to immune checkpoint inhibitors (ICIs).

As the second pan-tumor immunotherapy biomarker after MSI-H/dMMR, TMB holds significant potential for broad application. Combining TMB with other biomarkers such as PD-L1/MSI/TNB can improve the accuracy of identifying samples with immunotherapy-related biomarker profiles. Research into TMB's relationship with DNA repair pathways, tumor heterogeneity, and neoantigen generation further advances our understanding of the tumor immune microenvironment.

Key Features:

• Advanced Genomic Analysis Tool: Supports high-throughput analysis of tumor genomic instability markers TMB and MSI.
• Drug Development Accelerator: Accelerates immunotherapy drug development and biomarker discovery.
• Big Data Compatibility: Seamlessly integrates with multi-omics research ecosystems.

Variability of TMB Across Solid Tumors

TMB is a continuous variable exhibiting wide variation both between and within different cancer types. Certain cancers, such as lung cancer and head and neck cancer, demonstrate lower variability in TMB, while colon, bladder, and uterine cancers show higher variability. Cancers associated with chronic mutagen exposure (e.g., lung cancer and melanoma) generally exhibit high TMB, whereas leukemias and certain childhood cancers typically have low TMB.

• Relationship with MSI-H/dMMR: MSI-H tumors frequently display high TMB due to deficient DNA mismatch repair, with most MSI-H/dMMR cancers being colorectal or endometrial carcinomas. TMB and MSI-H status are strongly correlated across many cancer types, though exceptions exist in some cancers.
• Relationship with PD-L1 Expression: TMB and PD-L1 status are largely independent variables in most cancer types, although significant correlations exist between them in specific cancers. TMB and PD-L1 likely capture distinct tumor characteristics, and their combined use may better characterize samples with potential response profiles to ICIs than either biomarker alone.

TMB Workflow

Library Preparation

Comprehensive Gene Panel detects 641 cancer genes. Integrates biomarkers (TMB/MSI/MMR) for immunotherapy prediction.

Sequencing

illumina system

Data Anylysis

Analyze results using the CD Genomics Comprehensive TMB analysis module.