The pathogenesis of lung cancer associated with idiopathic pulmonary fibrosis (IPF) has remained largely uncharacterized. To provide insight into this condition, we undertook genomic profiling of IPF-associated lung cancer as well as of adjacent fibrosing lung tissue in surgical specimens. Isolated DNA and RNA from 17 IPF-associated non-small cell lung cancer and 15 paired fibrosing lung tissue specimens were analyzed by next-generation sequencing with a panel that targets 161 cancer-related genes. Somatic genetic alterations were frequently identified in TP53 (n = 6, 35.3%) and PIK3CA (n = 5, 29.4%) genes in tumor samples as well as in EGFR (n = 7, 46.7%), PIK3CA (n = 5, 33.3%), ERBB3 (n = 4, 26.7%), and KDR (n = 4, 26.7%) in IPF samples. Genes related to the RAS-RAF signaling pathway were also frequently altered in tumor (n = 7, 41.2%) and IPF (n = 3, 20.0%) samples. The number of somatic alterations identified in IPF samples was almost as large as that detected in paired tumor samples (81 vs 90, respectively). However, only 6 of the 81 somatic alterations detected in IPF samples overlapped with those in paired tumor samples. The accumulation of somatic mutations was thus apparent in IPF tissue of patients with IPF-associated lung cancer, and the RAS-RAF pathway was implicated in lung tumorigenesis. The finding that somatic alterations were not frequently shared between tumor and corresponding IPF tissue indicates that IPF-associated lung cancer does not develop through the stepwise accumulation of somatic alterations in IPF.
All Science Journal Classification (ASJC) codes
- Cancer Research