Variant-Specific Landscape of Mutual Exclusivity Among BRAF, EGFR, and KRAS Oncogenes in Human Cancer
Vaeyens, F.; Hetzel, J.-P.; Mernberger, M.; Eggermont, C.; Olsen, C.; Maes, K.; Vlaeminck, J.; Hes, F.; Pichler, M.; Giron, P.; Timofeev, O.; Noeparast, M.
Show abstract
In this cross-sectional study, we report the findings of our investigation into the mutual exclusivity (ME) and co-occurrence (CO) patterns of BRAF, KRAS, and EGFR mutations in human cancer. Our analysis acknowledges previously overlooked mutational subtypes with distinct clinical implications. Creating an automated R framework, we analyzed mutation data from 64807 unique cBioPortal samples, 1570 cell lines, and 2714 unique Belgian cancer samples. Consistently, across all three datasets, we observe that co-occurrence is less likely among class I BRAF, Hydrolysis KRAS, and Classical-like EGFR mutations. Bilateral variant-assigned CO matrices uncover novel inter-class and inter-type CO and ME scenarios, encompassing conventional and atypical mutations. Besides Class I BRAF, various mutation classes exhibit diverse CO patterns, justifying the need to refine mutational classifications. We provide a variant-specific database for precision oncology showcasing ME among three actionable oncogenes. These findings may guide the discovery of novel synthetically lethal interactions for targeted cancer therapy.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- APC Mutation marks an aggressive subtype of BRAF mutant colorectal cancers 95%
- Genomic profile in TGCT Mexican patients reveals a potential biomarker of sensitivity to platinum-based therapy 93%
- Use of high-plex data reveals novel insights into the tumour microenvironment of clear cell renal cell carcinoma 93%
Similar papers in this journal
- Analysis of Mutational Profile of Hypopharyngeal and Laryngeal Head and Neck Cancers Identifies KMT2C as a Potential Tumor Suppressor 95%
- Integrated molecular and pharmacological characterization of patient-derived xenografts from bladder and ureteral cancers identifies new potential therapies. 93%
- Evaluation of KRASG12C Inhibitor Responses in Novel Murine KRASG12C Lung Cancer Cell Line Models 92%
Similar papers in this journal
- MET variants with activating N-lobe mutations identified in hereditary papillary renal cell carcinomas still require ligand stimulation 94%
- Molecular and functional profiling unravels targetable vulnerabilities in colorectal cancer 94%
- Genomic analyses of high-grade neuroendocrine gynecological malignancies reveal a unique mutational landscape and therapeutic vulnerabilities 93%
Similar papers in this journal
- Tumor break load quantitates structural variant-associated genomic instability with biological and clinical relevance across cancers 94%
- A subset of lung cancer cases shows robust signs of homologous recombination deficiency associated genomic aberration based molecular signatures 94%
- Overcoming Resistance to BRAFV600E Inhibition in Melanoma by Deciphering and Targeting Personalized Protein Network Alterations 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.