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Published on: June 28, 2018
Integrated molecular characterization reveals the pathogenesis and therapeutic strategies of pulmonary blastoma
He Tian1,2, Zhenlin Yang1, Junhui Yang3
1Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
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.
Insights
Pulmonary blastoma (PB) is a rare lung cancer. Genomic analysis reveals DICER1 alterations and pathway dysregulation as key drivers, suggesting potential immunotherapy for select patients.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Pulmonary blastoma (PB) is a rare lung cancer with poorly understood pathogenesis.
- Current therapeutic options for PB are limited, necessitating further research into its molecular underpinnings.
Purpose of the Study:
- To elucidate the genomic and molecular characteristics of pulmonary blastoma.
- To identify potential pathogenesis mechanisms and therapeutic targets for PB.
Main Methods:
- Whole-exome sequencing (WES), RNA sequencing, and DNA methylation profiling were performed on seven PB patients.
- Multi-omics data from pulmonary sarcomatoid carcinoma (PSC) and pituitary blastoma (PitB) were integrated for comparative analysis.
Main Results:
- The highest genomic alteration rate in PB was observed in DICER1 (86%).
- DICER1 alterations, Wnt signaling pathway dysregulation, and IGF2 imprinting dysregulation were identified as potential pathogenesis mechanisms.
- PB molecular features are distinct from PSC and more closely resemble PitB. Low tumor mutation burden (TMB) and leukocyte fraction (LF) were noted, with some PD-L1 positivity and CD8-positive areas suggesting immunotherapy potential.
Conclusions:
- This study provides a comprehensive molecular profile of pulmonary blastoma.
- Novel insights into PB pathogenesis and potential therapeutic strategies, including immunotherapy for selected cases, are presented.
