Fusion gene recurrence in non-small cell lung cancers and its association with cigarette smoke exposure.
ChimeRScope
Fusion genes
The Cancer Genome Atlas (TCGA)
lung adenocarcinoma
smoke-induced gene fusions
Journal
Translational lung cancer research
ISSN: 2218-6751
Titre abrégé: Transl Lung Cancer Res
Pays: China
ID NLM: 101646875
Informations de publication
Date de publication:
Oct 2022
Oct 2022
Historique:
received:
12
02
2022
accepted:
22
08
2022
entrez:
17
11
2022
pubmed:
18
11
2022
medline:
18
11
2022
Statut:
ppublish
Résumé
Lung cancer remains the leading cause of cancer-related deaths in the US despite novel treatment protocols, with about 235,000 new cases and 131,000 deaths expected from this cancer in 2021 alone. Lung adenocarcinoma and squamous cell carcinoma, which are both subtypes of non-small cell lung cancer, account for most lung cancer cases, and comparing the molecular signatures in these two cancers can identify novel mechanisms that contribute to non-small cell lung cancer oncogenesis. We, in this study, performed a comprehensive gene fusion profiling of these cancers, which is understudied in lung cancers. Using an alignment-free fusion detection tool, 'ChimeRScope', we screened for gene fusions in lung adenocarcinoma and squamous cell carcinoma datasets from The Cancer Gene Atlas database. Fusion profiles in these two cancer subtypes were essentially different with minimal overlap. Our analysis revealed a positive association of smoking to fusion frequency in lung adenocarcinoma but not in squamous cell carcinoma and identified several fusion genes that could be explored as markers associated with cigarette smoke exposure. We also identified differentially regulated pathways linked to E2F, G2M checkpoint, and MTORC1 signaling upregulated and P53 pathway downregulated in samples containing high fusions in lung adenocarcinoma. Our results indicate that downregulation of the P53 pathway leads to higher gene fusion formation in lung adenocarcinoma. This manuscript provides a strong rationale for investigating the molecular mechanisms of cigarette smoke-induced gene fusion formation associated with lung cancer. Novel recurrent fusions associated with cigarette smoke were identified in our study, which could further be investigated for patient stratification, personalized therapy, and therapeutic monitoring.
Sections du résumé
Background
UNASSIGNED
Lung cancer remains the leading cause of cancer-related deaths in the US despite novel treatment protocols, with about 235,000 new cases and 131,000 deaths expected from this cancer in 2021 alone. Lung adenocarcinoma and squamous cell carcinoma, which are both subtypes of non-small cell lung cancer, account for most lung cancer cases, and comparing the molecular signatures in these two cancers can identify novel mechanisms that contribute to non-small cell lung cancer oncogenesis.
Methods
UNASSIGNED
We, in this study, performed a comprehensive gene fusion profiling of these cancers, which is understudied in lung cancers. Using an alignment-free fusion detection tool, 'ChimeRScope', we screened for gene fusions in lung adenocarcinoma and squamous cell carcinoma datasets from The Cancer Gene Atlas database. Fusion profiles in these two cancer subtypes were essentially different with minimal overlap.
Results
UNASSIGNED
Our analysis revealed a positive association of smoking to fusion frequency in lung adenocarcinoma but not in squamous cell carcinoma and identified several fusion genes that could be explored as markers associated with cigarette smoke exposure. We also identified differentially regulated pathways linked to E2F, G2M checkpoint, and MTORC1 signaling upregulated and P53 pathway downregulated in samples containing high fusions in lung adenocarcinoma. Our results indicate that downregulation of the P53 pathway leads to higher gene fusion formation in lung adenocarcinoma.
Conclusions
UNASSIGNED
This manuscript provides a strong rationale for investigating the molecular mechanisms of cigarette smoke-induced gene fusion formation associated with lung cancer. Novel recurrent fusions associated with cigarette smoke were identified in our study, which could further be investigated for patient stratification, personalized therapy, and therapeutic monitoring.
Identifiants
pubmed: 36386463
doi: 10.21037/tlcr-22-113
pii: tlcr-11-10-2022
pmc: PMC9641034
doi:
Types de publication
Journal Article
Langues
eng
Pagination
2022-2039Informations de copyright
2022 Translational Lung Cancer Research. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-113/coif). The authors have no conflicts of interest to declare.
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