Introduction/Background MLH1 is the MMR gene most frequently mutated or epimutated in endometrial cancer and its hypermethylation is found in the vast majority of MMR-deficient EC cases. The high rate of raw data accumulation with reference to cancer genomics as well as the development of bioinformatics algorithms necessary for the re-analysis of cohorts are key elements for obtaining new smart data.
Methodology In the present study we aimed to re-analyze a set of genomic data obtained by sequencing 197 EC samples and downloaded from the public database cBioPortal for Cancer Genomics - Endometrial Cancer (MSK, 2018). The aim of the research was to separate the genomic data into two cohorts based on the presence or absence of microsatellite instability and analyze the molecular profile of these cohorts.
Results As a result, two sets of data were obtained:
SM (Microsatellite Stability) – 153 samples
IM (Microsatellite Instability) – 25 samples
In the MS cohort, an almost 2-fold higher frequency of changes in the tumor suppressor TP53 is observed, while in IM – a considerably increased rate of PTEN, ARID1A, MLL2, JAK1, POLE, MLH1, MSH6, MSH2 and PMS1 mutations (figure 1).
SNV (Single Nucleotide Variation) classes in the IM group compared to SM have higher rates of T>C transitions that are associated with mutational signature no. 5 and lower C>G transversions - markers of signature 13 (figure 2).
TMB in the two study groups revealed an index of less than 10 mut/Mb in MS and more than 10 mut/Mb in MI (figure 3).
Conclusion Comparative analysis of molecular data in the two subtypes of CE reveals major differences in the mutational profile. A higher frequency of deletions with the displacement of the reading frame is observed in the SI cohort. TMB index in IM reveals tumors with MI have a better response to treatment with immune checkpoint inhibitors.
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