Details

Autor(en) / Beteiligte

• Salem, Mohamed E
• El-Refai, Sherif M
• Sha, Wei
• Puccini, Alberto
• Grothey, Axel
• George, Thomas J
• Hwang, Jimmy J
• O'Neil, Bert
• Barrett, Alexander S
• Kadakia, Kunal C
• Musselwhite, Laura W
• Raghavan, Derek
• Van Cutsem, Eric
• Tabernero, Josep
• Tie, Jeanne

Titel

Landscape of KRAS G12C , Associated Genomic Alterations, and Interrelation With Immuno-Oncology Biomarkers in KRAS -Mutated Cancers

Ist Teil von

• JCO precision oncology, 2022-05, Vol.6 (6), p.e2100245

Ort / Verlag

United States

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• Promising single-agent activity from sotorasib and adagrasib in -mutant tumors has provided clinical evidence of effective KRAS signaling inhibition. However, comprehensive analysis of -variant prevalence, genomic alterations, and the relationship between and immuno-oncology biomarkers is lacking. 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 variants. Logistic regression assessed comutations with other oncogenes and the association between variants and immuno-oncology biomarkers. Of the 79,004 samples assessed, 13,758 (17.4%) harbored mutations, with 1,632 (11.9%) harboring and 12,126 (88.1%) harboring other variants ( ). Compared with across all tumor subtypes, was more prevalent in females (56% 51%, false discovery rate-adjusted value [FDR- ] = .0006), current or prior smokers (85% 56%, FDR- < .0001), and patients age > 60 years (73% 63%, FDR- ≤ .0001). The most frequent variants across all subtypes were G12D (29.5%), G12V (23.0%), G12C (11.9%), G13D (6.5%), and G12R (6.2%). 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 -mutated, -mutated tumors were significantly associated with tumor mutational burden-high status (17.9% 8.4%, odds ratio [OR] = 2.38; FDR- < .0001). -mutated tumors exhibited a distinct comutation profile from -mutated tumors, including higher comutations of (20.59% 5.95%, OR = 4.10; FDR- < .01) and (15.38% 4.61%, OR = 3.76; FDR- < .01). This study presents the first large-scale, pan-cancer genomic characterization of . The mutation was more prevalent in females and older patients and appeared to be associated with smoking status. tumors exhibited a distinct comutation profile and were associated with tumor mutational burden-high status.