Detection of therapeutically relevant and concomitant rare somatic variants in colorectal cancer

Neoplasma. 2021 Oct 11:210616N804. doi: 10.4149/neo_2021_210616N804. Online ahead of print.ABSTRACTIn colorectal cancer, clinically relevant biomarkers are known for genome-guided therapy that can be detected by both first and next generation methods. The aim of our work was to introduce a robust NGS assay that will be able to detect, in addition to standard predictive single nucleotide-based biomarkers, even rare and concomitant clinically relevant variants. Another aim was to identify truncating mutations in APC and pathogenic variants in TP53 to divide patients into potentially prognostic groups. A multigene panel with hotspots in 50 cancer critical genes was used. Finally, 86 patients diagnosed with primary or metastatic colorectal cancer were enrolled. In total, there were identified 163 pathogenic variants, among them in the genes most recurrent mutated in CRC such as TP53 (49%), the RAS family genes KRAS and NRAS (47%), APC (43%), and PIK3CA (15%). In 30 samples, two driver mutations were present in one sample, 11 patients were without any mutations covered by this panel. In one patient, a novel variant in BRAF p.D594E was found, not previously seen in CRC, and was concomitant with KRAS p.G12A. In KRAS, a potentially sensitive mutation to anti-EGFR therapy p.A59T was found along with the PIK3CA missense variant p.E545K. It was possible to divide patients into groups based on the occurrence of truncating APC variant alone or concomitant with TP53 or KRAS. Our results de...

Source: Neoplasma - October 13, 2021 Category: Cancer & Oncology Authors: Peter Mikolajcik Zora Lasabova Dusan Loderer Marian Grendar Michal Kalman Ivana Kasubova Vincent Lucansky Alexander Johannes Wiederhold Juraj Marcinek Tatiana Burjanivova Eva Kudelova Martin Vojtko Adam Svec Lukas Plank Jan Janik Ludovit Laca Source Type: research