G12C: New clinical perspective in Lung Adenocarcinoma

Abstract

KRAS activating mutations are among the most frequent drivers in human cancer. However, the published series addressing the prevalence of KRAS G12C in lung adenocarcinoma are few and controversial. The objective of this study is to establish the prevalence of KRAS G12C mutation in lung adenocarcinoma as well as its possible coexistence with mutations in EGFR, ALK and BRAF. Also studying a possible morphological correlation with mutations in KRAS. Three hundred consecutive lung adenocarcinoma stage IIIb and IV cases diagnosed at the Dept. Pathology, Hospital Universitario de Canarias were included. Tumor genotyping was performed using the KRAS pyrosequencing kit (Qiagen). KRAS was mutated in approximately 35% of cases, being KRAS G12C the most frequent mutation. Mutated adenocarcinomas of KRAS could be seen also carrying mutations in EGFR or BRAF V600E. However, none was associated with ALK translocation. Therefore, KRAS mutations do not appear to be mutually exclusive with EGFR or BRAF mutations. No statistically significant association between histology subtypes of lung adenocarcinoma and mutations in KRAS was found, not even the mucinous phenotype, which has been suggested to harbor KRAS mutations in a higher proportion (p=0,318). Due to the recent development of KRAS inhibitors, it seems necessary to genotype KRAS in lung adenocarcinomas using protocols that can distinguish specific alleles since the therapy currently in clinical trials is mutation-specific. Pyrosequencing is a simple, low-cost and fast genopyting method for this purpose.