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- Title
Comprehensive pan-cancer genomic landscape of KRAS altered cancers and real-world outcomes in solid tumors.
- Authors
Lee, Jessica K.; Sivakumar, Smruthy; Schrock, Alexa B.; Madison, Russell; Fabrizio, David; Gjoerup, Ole; Ross, Jeffrey S.; Frampton, Garrett M.; Napalkov, Pavel; Montesion, Meagan; Schutzman, Jennifer L.; Ye, Xin; Hegde, Priti S.; Nagasaka, Misako; Oxnard, Geoffrey R.; Sokol, Ethan S.; Ou, Sai-Hong Ignatius; Shi, Zhen
- Abstract
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.
- Subjects
RAS oncogenes; CANCER prognosis; HEMATOLOGIC malignancies; COLORECTAL cancer; TUMORS; HEREDITARY nonpolyposis colorectal cancer
- Publication
NPJ Precision Oncology, 2022, Vol 6, Issue 1, p1
- ISSN
2397-768X
- Publication type
Article
- DOI
10.1038/s41698-022-00334-z