Variant‐Specific Landscape of Mutual Exclusivity Among BRAF, EGFR, and KRAS Oncogenes Reveals Overlap With Functionally Antagonistic Mutant Pairs
Freya Vaeyens, Jan‐Patrick Hetzel, Khaldoon Abdullah, Carolien Eggermont, Catharina Olsen, Marco Mernberger, Ken Maes, Jelle Vlaeminck, Rainer Claus, Dries Vanisterbecq, Frederik Hes, Martin Pichler, Philippe Giron, Oleg Timofeev, Maxim Noeparast · 2026
Read Variant‐Specific Landscape of Mutual Exclusivity Among BRAF, EGFR, and KRAS Oncogenes Reveals Overlap With Functionally Antagonistic Mutant Pairs by Freya Vaeyens, Jan‐Patrick Hetzel, Khaldoon Abdullah, Carolien Eggermont, Catharina Olsen, Marco Mernberger, Ken Maes, Jelle Vlaeminck, Rainer Claus, Dries Vanisterbecq, Frederik Hes, Martin Pichler, Philippe Giron, Oleg Timofeev, Maxim Noeparast (2026) in the Tower of Babel, a free online library of public-domain works preserved in clean, searchable text. No sign-up. The full text is served as a plain-text file at a predictable URL, where text is present: https://antarctic-labs.com/tower-of-babel/pmc-13432369.txt.
Description
Vaeyens and team mapped which mutations in three cancer genes refuse to appear together in the same tumor. The genes are BRAF, KRAS, and EGFR. The mapping ran variant by variant. The pattern is called mutual exclusivity, and it hints the paired changes harm cancer cells. They analyzed 64,807 tumor samples, 1,570 cancer cell lines, and 2,714 Belgian clinical cases.
Co-occurrence proved rare among class I BRAF, hydrolysis-type KRAS, and classical EGFR mutations across every dataset examined. Pairwise analysis surfaced new exclusivity relationships involving atypical variants. Some overlapped pairs already known to be synthetically lethal, meaning the combination kills cells. Forcing expression of one partner in cells carrying the other confirmed the antagonism experimentally. It slowed growth in both test systems used. Survival showed no consistent penalty for co-mutant tumors, except in EGFR-KRAS co-mutant lung cancer. The authors offer the map as a precision oncology reference.
Catalog record
| CREATOR | Freya Vaeyens, Jan‐Patrick Hetzel, Khaldoon Abdullah, Carolien Eggermont, Catharina Olsen, Marco Mernberger, Ken Maes, Jelle Vlaeminck, Rainer Claus, Dries Vanisterbecq, Frederik Hes, Martin Pichler, Philippe Giron, Oleg Timofeev, Maxim Noeparast |
|---|---|
| YEAR | 2026 |
| COLLECTION | PAPERS |
| FORMAT | TXT |
| FILE SIZE | 76 KB |
| VERSION | 1.0 |
| LICENSE | CC BY 4.0 |
| RIGHTS | CC BY |
| SOURCE | Europe PMC |