Genomic profiling by next-generation sequencing of idiopathic pulmonary fibrosis in Sardinia

<bold>Background:</bold> Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by progressive scarring of the lung. The pathogenesis of the condition appears complex, and uncertainties remain regarding clinical and molecular analogies with cancer, with no knowledge on somatic alterations within the fibrotic lung genome. <bold>Objective:</bold> We aimed to investigate for a genomic mutation profile using a next-generation sequencing (NGS)-based assay containing driver cancer-related genes in order to correlate the disease features with the molecular alterations into the main pathways controlling cell proliferation and survival. <bold>Methods:</bold> Genomic DNA samples from selected surgical lung tissue sections were obtained from 26 patients with IPF. The isolated DNA was analyzed by next-generation sequencing with a panel that targets 50 oncogenes. <bold>Results:</bold> We found somatic mutations in 9 genes, most frequently KIT (M541L variant: n = 9, 34.6%) and MYC (N26S variant: n = 4, 15.4%) genes. An upward trend in longer survival for those patients harboring mutations was observed. <bold>Conclusions:</bold> This is the first study, to our knowledge, that explores the genomic landscape of IPF tissue using a NGS approach. Although we detected somatic alterations in several oncogenes, none of them confer sensitivity to molecular targeted drugs. We warrant further, more extended NGS analysis of larger samples to provide further insight into the role of somatic mutations in the pathogenesis of IPF.