1. Exomic and epigenomic analysis of pulmonary blastoma.
- Author
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Alirezaie N, Chong AL, Kommoss FKF, Sabbaghian N, Camacho Valenzuela J, Pelletier D, Nadaf J, Kolekar SB, Sivapalan P, Evans MG, Thorner PS, Fiset PO, von Deimling A, and Foulkes WD
- Subjects
- Humans, Male, Female, Adult, Middle Aged, Mutation, Epigenomics methods, Aged, Exome Sequencing, Tumor Suppressor Protein p53 genetics, Exome genetics, Pulmonary Blastoma genetics, Pulmonary Blastoma pathology, DEAD-box RNA Helicases genetics, Ribonuclease III genetics, Lung Neoplasms genetics, Lung Neoplasms pathology, DNA Methylation, beta Catenin genetics
- Abstract
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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MGE is an employee of Caris Life Sciences and owns stock in Caris Life Sciences. POF has received paid consulting services and honoraria outside of this work from Amgen, Astellas, AstraZeneca, Bristol Meyers Squibb, EMD Serono, Incyte, Merck, Novartis, Pfizer, and Precision Rx-Dx. AvD is a co-founder and shareholder of Heidelberg Epignostix GmbH and declares patents related to methods for diagnosing tumors using antibodies from Dianova and related to DNA-methylation based methods for classifying tumor species. All other authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
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