This study reports the exome and genome sequences of 183 lung adenocarcinoma tumor/normal DNA pairs, revealing a mean exonic somatic mutation rate of 12.0 events/megabase. The analysis identified previously reported significantly mutated genes and novel candidates, including *U2AF1*, *RBM10*, and *ARID1A*. The mutation spectrum was analyzed, showing higher mutation rates in smokers compared to never-smokers, with distinct clusters correlating with smoking history and reported lung adenocarcinoma genes. Whole-genome sequencing revealed frequent structural rearrangements, such as in-frame exonic alterations in *EGFR* and *SIK2* kinases. The study also identified a novel in-frame deletion in *EGFR* that confers oncogenic activity. These findings advance the understanding of lung adenocarcinoma's genomic complexity and provide targets for biological characterization and therapeutic intervention.This study reports the exome and genome sequences of 183 lung adenocarcinoma tumor/normal DNA pairs, revealing a mean exonic somatic mutation rate of 12.0 events/megabase. The analysis identified previously reported significantly mutated genes and novel candidates, including *U2AF1*, *RBM10*, and *ARID1A*. The mutation spectrum was analyzed, showing higher mutation rates in smokers compared to never-smokers, with distinct clusters correlating with smoking history and reported lung adenocarcinoma genes. Whole-genome sequencing revealed frequent structural rearrangements, such as in-frame exonic alterations in *EGFR* and *SIK2* kinases. The study also identified a novel in-frame deletion in *EGFR* that confers oncogenic activity. These findings advance the understanding of lung adenocarcinoma's genomic complexity and provide targets for biological characterization and therapeutic intervention.