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

Autor: Jessica K. Lee, Smruthy Sivakumar, Alexa B. Schrock, Russell Madison, David Fabrizio, Ole Gjoerup, Jeffrey S. Ross, Garrett M. Frampton, Pavel Napalkov, Meagan Montesion, Jennifer L. Schutzman, Xin Ye, Priti S. Hegde, Misako Nagasaka, Geoffrey R. Oxnard, Ethan S. Sokol, Sai-Hong Ignatius Ou, Zhen Shi
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: npj Precision Oncology, Vol 6, Iss 1, Pp 1-14 (2022)
Druh dokumentu: article
ISSN: 2397-768X
DOI: 10.1038/s41698-022-00334-z
Popis: 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.
Databáze: Directory of Open Access Journals