Show simple item record

 
dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorSalem, Mohamed E.
dc.contributor.authorEl-Refai, Sherif M.
dc.contributor.authorSha, Wei
dc.contributor.authorPuccini, Alberto
dc.contributor.authorGrothey, Axel
dc.contributor.authorGeorge, Thomas J.
dc.contributor.authorTabernero Caturla, Josep
dc.date.accessioned2022-08-10T11:39:00Z
dc.date.available2022-08-10T11:39:00Z
dc.date.issued2022-03-23
dc.identifier.citationSalem ME, El-Refai SM, Sha W, Puccini A, Grothey A, George TJ, et al. Landscape of KRASG12C, Associated Genomic Alterations, and Interrelation With Immuno-Oncology Biomarkers in KRAS-Mutated Cancers. JCO Precis Oncol. 2022 Mar 23;6:e2100245.
dc.identifier.issn2473-4284
dc.identifier.urihttp://hdl.handle.net/11351/7982
dc.descriptionGenomic alterations; Mutated cancers; Immuno-oncology
dc.description.abstractPURPOSE Promising single-agent activity from sotorasib and adagrasib in KRASG12C-mutant tumors has provided clinical evidence of effective KRAS signaling inhibition. However, comprehensive analysis of KRAS-variant prevalence, genomic alterations, and the relationship between KRAS and immuno-oncology biomarkers is lacking. MATERIALS AND METHODS Retrospective analysis of deidentified records from 79,004 patients with various cancers who underwent next-generation sequencing was performed. Fisher's exact test evaluated the association between cancer subtypes and KRAS variants. Logistic regression assessed KRASG12C comutations with other oncogenes and the association between KRAS variants and immuno-oncology biomarkers. RESULTS Of the 79,004 samples assessed, 13,758 (17.4%) harbored KRAS mutations, with 1,632 (11.9%) harboring KRASG12C and 12,126 (88.1%) harboring other KRAS variants (KRASnon-G12C). Compared with KRASnon-G12C across all tumor subtypes, KRASG12C was more prevalent in females (56% v 51%, false discovery rate-adjusted P value [FDR-P] = .0006), current or prior smokers (85% v 56%, FDR-P < .0001), and patients age > 60 years (73% v 63%, FDR-P ≤ .0001). The most frequent KRAS variants across all subtypes were G12D (29.5%), G12V (23.0%), G12C (11.9%), G13D (6.5%), and G12R (6.2%). KRASG12C was most prevalent in patients with non–small-cell lung cancer (9%), appendiceal (3.9%), colorectal (3.2%), tumor of unknown origin (1.6%), small bowel (1.43%), and pancreatic (1.3%) cancers. Compared with KRASnon-G12C-mutated, KRASG12C-mutated tumors were significantly associated with tumor mutational burden-high status (17.9% v 8.4%, odds ratio [OR] = 2.38; FDR-P < .0001). KRASG12C-mutated tumors exhibited a distinct comutation profile from KRASnon-G12C-mutated tumors, including higher comutations of STK11 (20.59% v 5.95%, OR = 4.10; FDR-P < .01) and KEAP1 (15.38% v 4.61%, OR = 3.76; FDR-P < .01). CONCLUSION This study presents the first large-scale, pan-cancer genomic characterization of KRASG12C. The KRASG12C mutation was more prevalent in females and older patients and appeared to be associated with smoking status. KRASG12C tumors exhibited a distinct comutation profile and were associated with tumor mutational burden-high status.
dc.language.isoeng
dc.publisherAmerican Society of Clinical Oncology
dc.relation.ispartofseriesJCO Precision Oncology;6
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientia
dc.subjectCàncer
dc.subjectAnomalies cromosòmiques
dc.subjectGenòmica
dc.subject.meshNeoplasms
dc.subject.meshGenomics
dc.subject.meshBiomarkers, Tumor
dc.titleLandscape of KRASG12C, Associated Genomic Alterations, and Interrelation With Immuno-Oncology Biomarkers in KRAS-Mutated Cancers
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1200/PO.21.00245
dc.subject.decsneoplasias
dc.subject.decsgenómica
dc.subject.decsmarcadores tumorales
dc.relation.publishversionhttp://dx.doi.org/10.1200/PO.21.00245
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Salem ME, Sha W] Levine Cancer Institute, Atrium Health, Charlotte, USA. [El-Refai SM] Tempus Labs Inc, Chicago, USA. [Puccini A] University of Genoa, Ospedale Policlinico San Martino IRCCS, Genoa, Italy. [Grothey A] West Cancer Center, Germantown, USA. [George TJ] University of Florida, Gainesville, USA [Tabernero J] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. IOB-Quiron, UVic-UCC, Barcelona, Spain
dc.identifier.pmid35319967
dc.identifier.wos000777259500002
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record