Tumor mutational burden on cytological samples: A pilot study

Area of Science:

• Oncology
• Genomics
• Biomarker Discovery

Background:

• Immune-checkpoint inhibitors (ICIs) are crucial for advanced non-small cell lung cancer (NSCLC).
• Programmed death-ligand 1 (PD-L1) and high tumor mutational burden (TMB-H) are key predictive biomarkers for ICIs.
• Assessing TMB-H is challenging due to limited tissue availability from NSCLC patients.

Purpose of the Study:

• To evaluate the feasibility of analyzing tumor mutational burden (TMB) on cell blocks (CBs) from NSCLC patients.
• To determine if CBs can serve as a viable alternative to traditional tissue samples for TMB assessment.
• To explore the potential of CBs in improving biomarker-driven NSCLC treatment selection.

Main Methods:

• Eight pairs of NSCLC histological and cell block (CB) samples were analyzed.
• The Oncomine Tumor Mutational Load Assay was used on the Ion Torrent S5 GS next-generation sequencing (NGS) platform.
• Run metric parameters were compared between histological samples and CBs.

Main Results:

• Seventy-five percent (6/8) of CBs were successfully analyzed using a broad NGS panel.
• CBs yielded comparable results to matched histological specimens across various sequencing metrics.
• Key parameters like median total reads, mapped reads, and on-target read percentage were similar between CBs and histological samples.

Conclusions:

• This pilot study demonstrates the technical feasibility of assessing TMB on cell blocks (CBs).
• Cell blocks represent a promising alternative for TMB evaluation in NSCLC.
• This approach could overcome tissue acquisition challenges and facilitate the use of TMB as a predictive biomarker for ICIs.