Exomic and epigenomic analysis of pulmonary blastoma

Najmeh Alirezaie; Anne-Laure Chong; Felix K F Kommoss; Nelly Sabbaghian; Jose Camacho Valenzuela; Dylan Pelletier; Javad Nadaf; Shailesh B Kolekar; Pradeesh Sivapalan; Mark G Evans; Paul S Thorner; Pierre-Olivier Fiset; Andreas von Deimling; William D Foulkes

doi:10.1016/j.lungcan.2024.107916

Exomic and epigenomic analysis of pulmonary blastoma

Najmeh Alirezaie, Anne-Laure Chong, Felix K F Kommoss, Nelly Sabbaghian, Jose Camacho Valenzuela, Dylan Pelletier, Javad Nadaf, Shailesh B Kolekar, Pradeesh Sivapalan, Mark G Evans, Paul S Thorner, Pierre-Olivier Fiset, Andreas von Deimling, William D Foulkes

1 Citation (Scopus)

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.

Original language	English
Article number	107916
Journal	Lung Cancer
Volume	195
Pages (from-to)	107916
ISSN	0169-5002
DOIs	https://doi.org/10.1016/j.lungcan.2024.107916
Publication status	Published - Sept 2024

Keywords

Humans
Pulmonary Blastoma/genetics
DEAD-box RNA Helicases/genetics
Ribonuclease III/genetics
Lung Neoplasms/genetics
Male
DNA Methylation
Female
Adult
beta Catenin/genetics
Middle Aged
Mutation
Epigenomics/methods
Aged
Exome Sequencing
Tumor Suppressor Protein p53/genetics
Exome/genetics

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10.1016/j.lungcan.2024.107916

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Alirezaie, N., Chong, A.-L., Kommoss, F. K. F., Sabbaghian, N., Camacho Valenzuela, J., Pelletier, D., Nadaf, J., Kolekar, S. B., Sivapalan, P., Evans, M. G., Thorner, P. S., Fiset, P.-O., von Deimling, A., & Foulkes, W. D. (2024). Exomic and epigenomic analysis of pulmonary blastoma. Lung Cancer, 195, 107916. Article 107916. https://doi.org/10.1016/j.lungcan.2024.107916

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title = "Exomic and epigenomic analysis of pulmonary blastoma",

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.",

keywords = "Humans, Pulmonary Blastoma/genetics, DEAD-box RNA Helicases/genetics, Ribonuclease III/genetics, Lung Neoplasms/genetics, Male, DNA Methylation, Female, Adult, beta Catenin/genetics, Middle Aged, Mutation, Epigenomics/methods, Aged, Exome Sequencing, Tumor Suppressor Protein p53/genetics, Exome/genetics",

author = "Najmeh Alirezaie and Anne-Laure Chong and Kommoss, \{Felix K F\} and Nelly Sabbaghian and \{Camacho Valenzuela\}, Jose and Dylan Pelletier and Javad Nadaf and Kolekar, \{Shailesh B\} and Pradeesh Sivapalan and Evans, \{Mark G\} and Thorner, \{Paul S\} and Pierre-Olivier Fiset and \{von Deimling\}, Andreas and Foulkes, \{William D\}",

year = "2024",

month = sep,

doi = "10.1016/j.lungcan.2024.107916",

language = "English",

volume = "195",

pages = "107916",

journal = "Lung Cancer",

issn = "0169-5002",

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T1 - Exomic and epigenomic analysis of pulmonary blastoma

AU - Alirezaie, Najmeh

AU - Chong, Anne-Laure

AU - Kommoss, Felix K F

AU - Sabbaghian, Nelly

AU - Camacho Valenzuela, Jose

AU - Pelletier, Dylan

AU - Nadaf, Javad

AU - Kolekar, Shailesh B

AU - Sivapalan, Pradeesh

AU - Evans, Mark G

AU - Thorner, Paul S

AU - Fiset, Pierre-Olivier

AU - von Deimling, Andreas

AU - Foulkes, William D

PY - 2024/9

Y1 - 2024/9

N2 - 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.

AB - 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.

KW - Humans

KW - Pulmonary Blastoma/genetics

KW - DEAD-box RNA Helicases/genetics

KW - Ribonuclease III/genetics

KW - Lung Neoplasms/genetics

KW - Male

KW - DNA Methylation

KW - Female

KW - Adult

KW - beta Catenin/genetics

KW - Middle Aged

KW - Mutation

KW - Epigenomics/methods

KW - Aged

KW - Exome Sequencing

KW - Tumor Suppressor Protein p53/genetics

KW - Exome/genetics

UR - https://www.scopus.com/pages/publications/85200717377

U2 - 10.1016/j.lungcan.2024.107916

DO - 10.1016/j.lungcan.2024.107916

M3 - Journal article

C2 - 39121796

SN - 0169-5002

VL - 195

SP - 107916

JO - Lung Cancer

JF - Lung Cancer

M1 - 107916

ER -

Exomic and epigenomic analysis of pulmonary blastoma

Abstract

Keywords

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