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

Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by progressive scarring of the lung and histopathological features of Usual Interstitial Pneumonia (UIP). 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. We aimed to explore the genomic profile of lung tissue from patients with IPF, and to investigate any relevant molecular alterations in cancer-related genes. To do so, we selected surgical lung tissue specimens from 33 patients. The isolated DNA from these samples was analysed by next-generation sequencing (NGS) with a panel that targets 49 oncogenes. Our research uncovered 87 somatic alterations in a total of 12 oncogenes. The presence of ≥ 3 variants correlated positively with longer survival rates (p = 0.049). We also negatively correlated the presence of a KIT gene variant with the presence of a radiological UIP pattern. To our knowledge, this is the first study that explores the genomic landscape of IPF tissue using NGS technology. Although we detected somatic alterations in several oncogenes, none of them confer sensitivity to known molecular targeted drugs. We observed longer survival in those patients harbouring ≥ 3 mutations. We warrant further, more extended NGS analysis of larger cohorts to provide further insight into the role of somatic mutations in the pathogenesis of IPF.