Purpose of review
The mutational landscape in lung adenocarcinoma (LADC) is broadly recognized, particularly regarding the presence of the epidermal growth factor receptor (EGFR
) mutation in non-smokers. However, even in the EGFR
canonical-mutant LADC, other accompanying alterations surface which may have a major impact in prognosis and open possibilities to explore new therapeutic approaches.
Complex genomic rearrangements, including chromothripsis and chromoplexy, are the origin of most-known fusion oncogenes, including echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase, Cluster of Differentiation 74-c-ros oncogene 1, and kinesin-1 heavy chain- rearranged during transfection. Quite often LADCs driven by fusion oncogenes are accompanied by SET domain containing 2
(SETD2) mutations. SETD2 mutations have been described in renal cancer and have been related to cisplatin resistance in LADCs. Suppression of the SETD2 function inhibits the signal transducer and transcription activator function and the interferon-signaling pathway, which could partially explain the lack of effectiveness of immunotherapy in LADCs driven by fusion oncogenes.
Summary Targeted next-generation sequencing
of DNA in the tumor tissue or in the circulating plasma of LADC is becoming indispensable for the accurate classification of LADCs that can receive appropriate targeted therapy. It is unquestionable that additional techniques, like RNA sequencing or the nCounter technology, can accomplish accurate assessment of an ample array of fusion oncogenes involved in LADCs.