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Updated: Jun 17, 2025
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Exomic and epigenomic analysis of pulmonary blastoma
Najmeh Alirezaie1, Anne-Laure Chong1, Felix K F Kommoss2
1Cancer Axis, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.
Objective:
Pulmonary blastoma is a rare, biphasic, adult-onset lung tumor. In this study, we investigate whether DICER1 pathogenic variants are a feature of pulmonary blastomas through in-depth analysis of the molecular events defining them.
Methods:
We performed exome-wide sequencing and DNA methylation profiling of 8 pulmonary blastomas from 6 affected persons.
Results:
We identified biallelic somatic DICER1 pathogenic variants in 7 of 8 cases. The remaining case had a solitary missense pathogenic variant in the RNase IIIb domain of DICER1. Six of 8 cases carried a CTNNB1 hotspot variant and 4 of 8 had a somatic pathogenic variant in TP53. Methylation analysis showed that the pulmonary blastomas clustered with other DICER1-mutated tumors and not with other more common types of lung cancer.
Conclusion:
We conclude somatic DICER1 pathogenic variants are the major driver of pulmonary blastoma and are likely to act in conjunction with CTNNB1 hotspot variants that are often present.
