The distinct features of the chromosomal unstable tumors compared to genomic stable tumors
2Department of Hematology, Oncology and Cancer Immunology; Berlin, Germany., Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin,
3Berlin Institute of Health at Charité, Universitätsmedizin Berlin; Berlin, Germany.
Recently, colorectal cancer (CRC) was classified into 4 molecular subtypes based on their genomic instability: microsatellite instability (MSI), hyper-mutation of single nucleotide-variant (HM), chromosomal instability (CIN) and genomic stability (GS). The MSI and HM are known to differ from the other two in many features: the mutated genes, age of onset, etc. However, the newly classified subtypes CIN and GS were found to differ in very few features; mainly the existence of TP53 in CIN samples, which is expected as TP53 leads to increased chromosomal aberrations. Besides that, the features that were found to differ between CIN and GS were not statistically significant. However, it is not clear if the lack of any significant difference is due to a lack of statistical power, as GS is a small subtype.
In order to increase the number of samples, we developed a new method that classifies CIN/GS from panel sequencing of only ~400 genes and thus allows us to use the many clinical samples that are available. This approach allowed us to analyze ~2500 samples and to greatly improve our statistical power.
Using this large dataset,we still found almost no difference between CIN and GS CRC samples. However, when applying our method to other tumor types with similar subtypes (i.e. stomach and endometrial), we found that endometrial CIN and GS differ substantially, both in the mutated genes as well as phenotypic features such as survival rate. This suggests that in endometrial cancer CIN and GS should be treated differently.