Assessment of tumor mutation burden calculation from gene panel sequencing data

Area of Science:

• Oncology
• Genomics
• Immunotherapy

Background:

• High tumor mutation burden (TMB) is a key biomarker for immune checkpoint blockade efficacy in cancers like melanoma and lung cancer.
• Traditionally, TMB is determined via whole genome or whole exome sequencing (WES).
• Targeted gene panels offer a clinically feasible alternative for TMB estimation.

Purpose of the Study:

• To systematically analyze TMB distribution and mutation patterns across 15 cancer types.
• To evaluate the correlation between TMB calculated from WES and targeted gene panels.
• To develop and validate a pan-cancer TMB panel for immunotherapy applications.

Main Methods:

• Utilized somatic mutation data from The Cancer Genome Atlas (TCGA) across 15 cancer types.
• Compared TMB calculations from whole exome sequencing (WES) with various targeted gene panels.
• Developed and assessed a novel pan-cancer TMB panel.

Main Results:

• Identified distinct TMB distributions and gene mutation preferences across different cancer types.
• Demonstrated that a proposed pan-cancer TMB panel exhibits a high correlation with WES-derived TMB.
• The developed panel outperformed other tested panels in TMB estimation accuracy.

Conclusions:

• Targeted gene panels can reliably estimate tumor mutation burden (TMB) for clinical use.
• The proposed pan-cancer panel serves as a valuable tool for designing TMB-based gene panels.
• This facilitates the identification of patients eligible for immunotherapy across diverse cancer types.