AUTHOR=Chalela Roberto , González-García Jose Gregorio , Khilzi Karys , Curull Víctor , Sánchez-Font Albert , Longarón Raquel , Rodrigo-Calvo María Teresa , Martín-Ontiyuelo Clara , Gea Joaquim , Bellosillo Beatríz TITLE=EGFR and KRAS Mutations in Lung Parenchyma of Subjects With EGFR/KRAS Wild-Type Lung Adenocarcinoma JOURNAL=Pathology and Oncology Research VOLUME=27 YEAR=2021 URL=https://www.por-journal.com/journals/pathology-and-oncology-research/articles/10.3389/pore.2021.598292 DOI=10.3389/pore.2021.598292 ISSN=1532-2807 ABSTRACT=

The 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.