Chalela Rengifo, Roberto José, 1985-González-García, José GregorioKhilzi, KarysCurull Serrano, VíctorSánchez Font, AlbertLongarón Rozalen, RaquelRodrigo Calvo, Maria TeresaMartín-Ontiyuelo, ClaraGea Guiral, JoaquimBellosillo Paricio, Beatriz2021-10-062021-10-062021Chalela R, González-García JG, Khilzi K, Curull V, Sánchez-Font A, Longarón R, Rodrigo-Calvo MT, Martín-Ontiyuelo C, Gea J, Bellosillo B. EGFR and KRAS mutations in lung parenchyma of subjects with EGFR/KRAS wild-type lung adenocarcinoma. Pathol Oncol Res. 2021;27:598292. DOI: 10.3389/pore.2021.5982921219-4956http://hdl.handle.net/10230/48576The acquisition of driver mutations in non-tumoral cells appears to be very important during the carcinogenesis of adenocarcinoma (ADC). Recent studies suggest that cancer-related mutations may not necessarily be present only in malignant cells, but also in histologically "healthy cells". Objective: to demonstrate the presence of EGFR or KRAS mutations in non-tumoral lung cells in subjects with ADC and negative mutational status. Results: mutations in EGFR or KRAS oncogenes were identified in the normal lung in 9.7% of the subjects. Exon 21 substitution L858R in EGFR was detected in two cases while the exon 19 deletion E746-A750 in the EGFR, the G12C and G12D substitutions in the KRAS were detected once. One patient presented three different mutations in the normal lung parenchyma (EGFR_L858R, KRAS_G12C and KRAS_G12D). The negative-mutation status of the tumor and the mutations detected in the "normal lung" were confirmed using highly sensitive and specific TaqMan PCR (CAST-PCR). No differences were found in terms of progression, progression-free survival or overall survival during the 18 months follow-up. Conclusions: These results confirm the presence of driver mutations in the histologically normal lung parenchyma cells in the absence of mutations coexisting with the primary tumor.application/pdfeng© 2021 Chalela, González-García, Khilzi, Curull, Sánchez-Font, Longarón, Rodrigo-Calvo, Martín-Ontiyuelo, Gea and Bellosillo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.info:eu-repo/semantics/articlehttp://dx.doi.org/10.3389/pore.2021.598292EGFR–epidermal growth factor receptorKRASPrognosisAdenocacinoma lungDriver mutationinfo:eu-repo/semantics/openAccess