Mutational profiles of lung adenocarcinoma subtypes.

Abstract

e21517 Background: Genomic profiling of lung adenocarcinoma has been studied, however, different histological subtypes were not carefully distinguished, especially in patients with mixed subtypes. Methods: Fifty-three invasive adenocarcinoma (IA) FFPE samples from lung cancer patients with detailed histological classifications were panel sequenced and analyzed. Results: Among the 53 IAs, acinar (n = 42), lepidic (n = 34) and papillary (n = 25) were most dominant subtypes and were frequently mixed with other types. Zero to 14 mutations were identified in each sample (median = 4). Thirteen of the 42 (31%) tumors containing acinar subtype harbored TP53 mutations, while none of the 11 (0%) acinar negative tumors harbor TP53 mutation; six of the 42 (14.3%) acinar positive had RBM10 mutations, while 5 of the 11 (45.4%) acinar negative had RBM10 mutations. Three of the 34 (8.8%) tumors with lepidic subtypes harbored TP53 mutations, while 10 of the 19 (52.6%) lepidic negative tumors harbored TP53 mutations; Ten of 34 (29.4%) lepidic positive tumors harbored RBM10 mutations, while 1 of the 19 (5.3%) lepidic negative tumors harbored RBM10 mutations. All papillary tumors were mixed with other subtypes. Conclusions: Different histological subtypes have different mutational features. Acinar subtypes harbor more TP53 and less RBM10 mutations than acinar negative tumors; lepidic subtypes harbor less TP53 and more RBM10 mutations than lepidic negative tumors. Lack of mucinous, micropapillary and solid subtypes requires further study to analyze their mutational signatures.