In 49 patients, 15 showed intratumoral heterogeneity in microsatellite instability, with distinct MSI-H and MSS subclones within tumors.
Is microsatellite instability (MSI) a heterogeneous phenomenon within tumors?
Intratumoral heterogeneity in microsatellite instability exists, questioning its use as a binary biomarker and suggesting that accounting for this heterogeneity could improve its predictive value.
Absolute Event Rate: 0% vs 0%
Intratumoral heterogeneity complicates the interpretation of single-test biomarkers. Microsatellite instability (MSI) is one such biomarker, which is used to guide immune checkpoint inhibitor treatment by classifying samples as having high microsatellite instability (MSI-H) or as microsatellite stable (MSS). However, it is unknown whether MSI itself is a heterogeneous phenomenon. To test this, we curated data from several single-cell RNA sequencing studies with clinical MSI status and developed a computational pipeline that quantifies intratumoral heterogeneity in MSI. Out of 49 individuals, 15 showed evidence of divergence in MSI status between clusters of cancer cells, and most had distinct MSI-H and MSS subclones. These results question the use of MSI as a binary biomarker, and we hypothesize that accounting for heterogeneity could improve its use as a predictive biomarker. Further studies are required to determine the frequency of MSI heterogeneity at the population level and whether it can have clinical implications.
Anthony et al. (Fri,) reported a other. In 49 patients, 15 showed intratumoral heterogeneity in microsatellite instability, with distinct MSI-H and MSS subclones within tumors.