Comprehensive pan-cancer genomic landscape of KRAS altered cancers and real-world outcomes in solid tumors

• Published in: NPJ precision oncology Vol. 6; no. 1; pp. 91 - 14
• Main 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.12.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/67/69; 692/308/409; 692/4017; 692/53/2423; Blood cancer; Cancer; Cancer Research; Clinical outcomes; Colorectal cancer; Gene Therapy; Genomics; Human Genetics; Internal Medicine; Medicine; Medicine & Public Health; Mutation; Oncology; Pediatrics; Tumors
• ISSN: 2397-768X; 2397-768X
• DOI: 10.1038/s41698-022-00334-z

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.