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Tumor mutational burden (TMB) can function as a biomarker for response to immunotherapy. Understanding how to accurately test TMB and understanding the implications of variation in the results can inform treatment. This study, published in Clinical Research (Excluding Clinical Trials), analyzed the genomic profiles of patients with cancer to assess TMB prevalence and variability, and its relationship with other biomarkers.

The study relied on pan-tumor genomic profiles from 246,806 patients that were tested as a part of their routine clinical care. A total of 3,402 patients with 38 tumor types with multiple longitudinal tissue biopsies were identified and analyzed to determine changes in TMB status.

Ultimately, it was found that skin, lung, bladder, uterus, and endometrial tumors all showed a high prevalence of TMB, while gastrointestinal (GI) tumors showed a much lower prevalence. Moreover, a co-occurrence of TMB and microsatellite instability (MSI) was found, particularly in GI tumors.

The researchers concluded that changes in TMB may be partially the result of ongoing therapies or mutational processes. They also noted that TMB is highly variable as a biomarker, and thus, the cutoff for clinical validation can be challenging to determine. They suggest a cutoff of 10 mutations/megabase is stable across tumor types and potentially across treatments [1].

Source:

[1] Sivakumar, S., Sokol, E. S., Frampton, G. M., Fabrizio, D., Alexander, B., Hegde, P. S., & Grothey, A. (2021). Abstract 472: Tumor mutational burden reveals tumor-specific patterns with intra-patient stability from multiple longitudinal tissue biopsies from 3,402 patients. Clinical Research (Excluding Clinical Trials)https://doi.org/10.1158/1538-7445.am2021-472

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