The pattern of KRAS mutations in non-small cell lung cancer (NSCLC): A retrospective study from south-eastern Georgia.

Abstract

e15110 Background: Carcinogenic Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation is a common oncogenic mutation found in lung cancer. It is a gain-of-function mutation that is the most commonly mutated oncogene in NSCLC; occurs in about 30% of all lung adenocarcinomas. A lot of progress has been made in targeted therapies against other oncogenic drivers, such as EGFR, HER2, MET, BRAF mutations. However, KRAS mutant lung cancer is still very difficult to manage and options are limited. Most recently, K-ras G12C has a newly approved novel targeted therapy. Different KRAS mutations may also represent different outcomes. Multiple studies have been looking into mutant KRAS and investigating it in the clinical relevance in lung cancer. Here we characterize a cohort of KRAS subtypes in all tumor types of lung cancer from south-eastern Georgia. Methods: This is a retrospective study that evaluated patients with K-ras mutant lung cancer from Augusta, Georgia geographical area. Samples were obtained from May 15th, 2015 to January 4th, 2022 and patients with KRAS mutant lung cancers were identified via Guardant platform. Results: In our cohort of patients, a total of 622 patients were evaluated in which 531 patients had a lung cancer diagnoses. Of those 531 patients, 383 had lung adenocarcinoma, 109 lung squamous cell, 34 NSCLC, 3 small cell, 1 lung carcinoid, and 1 large cell lung carcinoma. Of the 531 lung cancer patients, 14 (2.6%) patients expressed KRAS mutation with 12 (3.1%) patients expressing KRAS with lung adenocarcinoma. NRAS was expressed separately in 2 patients and HRAS was expressed separately in 1 patient. Our cohort of patients with K-ras mutant NSCLC had TP53 co-mutation in 78 (14%), MSI-High mutation in 60 (11%) patients, and EGFR mutation in 23 (4.3%) patients. The most common KRAS subtype in lung adenocarcinoma was G12V (42%), G12C (42%), and Y64D (8.3%). Two patients were unable to identify the type of the K-ras mutation. In addition, 92% of the carriers for KRAS mutation in lung adenocarcinoma were males. Its been noted that G12C mutation is the most common; however, in south-east Georgia, G12V is as common as G12C. Conclusions: KRAS mutation subtypes have distinct genomic landscape which requires further assessment to guide future therapeutic development. In the geographical area of Augusta, Georgia, KRAS subtype G12V is as common as G12C.