Mutational distinction between adenocarcinoma in situ, minimally invasive adenocarcinoma and invasive adenocarcinoma in lung cancer patients with multiple tumors.

Abstract

e21089 Background: Lung adenocarcinoma is the most popular lung cancer type, and it can be classified as adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IA) based on histology. The mutational similarities and differences have not been discussed in these subtypes. Methods: Targeted deep sequencing was performed on 31 lung adenocarcinomas with matched blood samples from 15 patients with multiple tumors. We compared mutations among each subtype. Results: The 31 tumors consisted of 10 AIS, 6 MIA and 15 IA subtypes; the median mutation number in each type was 1, 1 and 3 respectively. Eleven, six and fifty-three mutations were identified in AIS, MIA, and IA respectively. Among all the 67 mutations, only EGFR_p.L858R was found in all three types; BRAF_p.K601E was found in AIS and IA. Conclusions: AIS, MIA and IA harbor distinct mutational signatures, except for several popular driver mutations, suggesting their distinct origin and evolution path.