Effects of sequencing parameters and panel size on mutational burden calculations

Ramifications of varying cancer panel sizes and read depths on the calculation of TMB scores

Immunotherapies are an emerging approach for cancer treatment that leverage the power of the immune system to attack cancer cells. By targeting immune check-point pathways such as PD-1, these treatments have been highly effective for some patients diagnosed with skin, bladder, lung, or kidney cancer. However, response rates for these treatments vary, making it beneficial to identify patients who are likely to respond to the treatment.

Qualitative methods for predicting immunotherapy response are available but are technically challenging and subjective. An emerging quantitative predictor of immunotherapy response, tumor mutational burden (TMB), measures the number of somatic mutations per Mb of the genome. TMB calculations using whole exome data have been shown to correlate with patient response to immunotherapies. However, derivation of this score is not well characterized, nor is the score universally performed across laboratories.

In this poster, we describe the ramifications of varying cancer panel sizes and read depths on the calculation of TMB scores. We show impacts of gene content and sequencing depth for providing a range of burden scores that could be used for setting appropriate thresholds for determining therapeutic implications.

Authors: Natalie Mola, Scott Yourstone, Victor Weigman

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