Integrated molecular characterization reveals the pathogenesis and therapeutic strategies of pulmonary blastoma

Background: Pulmonary blastoma (PB) is a rare subtype of lung cancer. Currently, the underlying pathogenesis mechanisms of PB have not been fully illustrated, and the therapeutic approach for this entity is limited. Methods: Whole-exome sequencing (WES), RNA sequencing, and DNA methylation profiling are applied to seven PB patients. Multi-omics data of pulmonary sarcomatoid carcinoma (PSC) and pituitary blastoma (PitB) from previous studies are invoked to illuminate the associations among PB and these malignacies. Results: We portray the genomic alteration spectrum of PB and find that DICER1 is with the highest alteration rate (86 %). We uncover that DICER1 alterations, Wnt signaling pathway dysregulation and IGF2 imprinting dysregulation are the potential pathogenesis mechanisms of PB. Moreover, we reveal that the integrated molecular features of PB are distinct from PSC, and the molecular characteristics of PB are more similar to PitB than to PSC. Pancancer analysis show that the tumor mutation burden (TMB) and leukocyte fraction (LF) of PB are low, while some cases are positive for PD-L1 or have CD8-positive focal areas, implying the potential applicability of immunotherapy in selected PB patients. Conclusion: This study depicts the integrated molecular characteristics of PB and offers novel insights into the pathogenesis and therapeutic strategies of PB.