Genomic architecture of FGFR2 fusions in cholangiocarcinoma and its implication for molecular testing.
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
11 2022
11 2022
Historique:
received:
07
02
2022
accepted:
29
06
2022
revised:
23
06
2022
pubmed:
24
7
2022
medline:
14
10
2022
entrez:
23
7
2022
Statut:
ppublish
Résumé
Cholangiocarcinoma (CCA) is a primary malignancy of the biliary tract with a dismal prognosis. Recently, several actionable genetic aberrations were identified with significant enrichment in intrahepatic CCA, including FGFR2 gene fusions with a prevalence of 10-15%. Recent clinical data demonstrate that these fusions are druggable in a second-line setting in advanced/metastatic disease and the efficacy in earlier lines of therapy is being evaluated in ongoing clinical trials. This scenario warrants standardised molecular profiling of these tumours. A detailed analysis of the original genetic data from the FIGHT-202 trial, on which the approval of Pemigatinib was based, was conducted. Comparing different detection approaches and displaying representative cases, we described the genetic landscape and architecture of FGFR2 fusions in iCCA and show biological and technical aspects to be considered for their detection. We elaborated parameters, including a suggestion for annotation, that should be stated in a molecular diagnostic FGFR2 report to allow a complete understanding of the analysis performed and the information provided. This study provides a detailed presentation and dissection of the technical and biological aspects regarding FGFR2 fusion detection, which aims to support molecular pathologists, pathologists and clinicians in diagnostics, reporting of the results and decision-making.
Sections du résumé
BACKGROUND
Cholangiocarcinoma (CCA) is a primary malignancy of the biliary tract with a dismal prognosis. Recently, several actionable genetic aberrations were identified with significant enrichment in intrahepatic CCA, including FGFR2 gene fusions with a prevalence of 10-15%. Recent clinical data demonstrate that these fusions are druggable in a second-line setting in advanced/metastatic disease and the efficacy in earlier lines of therapy is being evaluated in ongoing clinical trials. This scenario warrants standardised molecular profiling of these tumours.
METHODS
A detailed analysis of the original genetic data from the FIGHT-202 trial, on which the approval of Pemigatinib was based, was conducted.
RESULTS
Comparing different detection approaches and displaying representative cases, we described the genetic landscape and architecture of FGFR2 fusions in iCCA and show biological and technical aspects to be considered for their detection. We elaborated parameters, including a suggestion for annotation, that should be stated in a molecular diagnostic FGFR2 report to allow a complete understanding of the analysis performed and the information provided.
CONCLUSION
This study provides a detailed presentation and dissection of the technical and biological aspects regarding FGFR2 fusion detection, which aims to support molecular pathologists, pathologists and clinicians in diagnostics, reporting of the results and decision-making.
Identifiants
pubmed: 35871236
doi: 10.1038/s41416-022-01908-1
pii: 10.1038/s41416-022-01908-1
pmc: PMC9553883
doi:
Substances chimiques
FGFR2 protein, human
EC 2.7.10.1
Receptor, Fibroblast Growth Factor, Type 2
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1540-1549Informations de copyright
© 2022. The Author(s).
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