Journal
NPJ PRECISION ONCOLOGY
Volume 6, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41698-022-00334-z
Keywords
-
Categories
Funding
- Foundation Medicine Inc, Cambridge, MA, USA
- [(2020) 31]
- [S274-S302]
- [10.1016/annonc/annonc266]
- [2233]
- [(2021) 81]
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Recent clinical development of KRAS inhibitors has increased interest in the genomic landscape of KRAS-altered cancers. Comprehensive genomic profiling revealed the prevalence of KRAS alterations and identified co-alterations and biomarkers associated with KRAS mutations.
Recent clinical development of KRAS inhibitors has heightened interest in the genomic landscape of KRAS-altered cancers. We performed a pan-cancer analysis of KRAS-altered samples from 426,706 adult patients with solid or hematologic malignancies using comprehensive genomic profiling; additional analyses included 62,369 liquid biopsy and 7241 pediatric samples. 23% of adult pan-cancer samples had KRAS alterations; 88% were mutations, most commonly G12D/G12V/G12C/G13D/G12R, and prevalence was similar in liquid biopsies. Co-alteration landscapes were largely similar across KRAS mutations but distinct from KRAS wild-type, though differences were observed in some tumor types for tumor mutational burden, PD-L1 expression, microsatellite instability, and other mutational signatures. Prognosis of KRAS-mutant versus other genomic cohorts of lung, pancreatic, and colorectal cancer were assessed using a real-world clinicogenomic database. As specific KRAS inhibitors and combination therapeutic strategies are being developed, genomic profiling to understand co-alterations and other biomarkers that may modulate response to targeted or immunotherapies will be imperative.
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