Recurrent and novel fusions detected by targeted RNA sequencing as part of the diagnostic workflow of soft tissue and bone tumours.
Humans
Bone Neoplasms
/ genetics
Soft Tissue Neoplasms
/ genetics
Female
Adult
Male
Middle Aged
Workflow
In Situ Hybridization, Fluorescence
Adolescent
Aged
Sequence Analysis, RNA
Child
Young Adult
Gene Fusion
Biomarkers, Tumor
/ genetics
Child, Preschool
Aged, 80 and over
Oncogene Proteins, Fusion
/ genetics
FISH
RNA‐seq
bone tumours
sarcomas
soft tissue tumours
Journal
The journal of pathology. Clinical research
ISSN: 2056-4538
Titre abrégé: J Pathol Clin Res
Pays: England
ID NLM: 101658534
Informations de publication
Date de publication:
May 2024
May 2024
Historique:
revised:
16
03
2024
received:
04
12
2023
accepted:
15
04
2024
medline:
13
5
2024
pubmed:
13
5
2024
entrez:
13
5
2024
Statut:
ppublish
Résumé
The identification of gene fusions has become an integral part of soft tissue and bone tumour diagnosis. We investigated the added value of targeted RNA-based sequencing (targeted RNA-seq, Archer FusionPlex) to our current molecular diagnostic workflow of these tumours, which is based on fluorescence in situ hybridisation (FISH) for the detection of gene fusions using 25 probes. In a series of 131 diagnostic samples targeted RNA-seq identified a gene fusion, BCOR internal tandem duplication or ALK deletion in 47 cases (35.9%). For 74 cases, encompassing 137 FISH analyses, concordance between FISH and targeted RNA-seq was evaluated. A positive or negative FISH result was confirmed by targeted RNA-seq in 27 out of 49 (55.1%) and 81 out of 88 (92.0%) analyses, respectively. While negative concordance was high, targeted RNA-seq identified a canonical gene fusion in seven cases despite a negative FISH result. The 22 discordant FISH-positive analyses showed a lower percentage of rearrangement-positive nuclei (range 15-41%) compared to the concordant FISH-positive analyses (>41% of nuclei in 88.9% of cases). Six FISH analyses (in four cases) were finally considered false positive based on histological and targeted RNA-seq findings. For the EWSR1 FISH probe, we observed a gene-dependent disparity (p = 0.0020), with 8 out of 35 cases showing a discordance between FISH and targeted RNA-seq (22.9%). This study demonstrates an added value of targeted RNA-seq to our current diagnostic workflow of soft tissue and bone tumours in 19 out of 131 cases (14.5%), which we categorised as altered diagnosis (3 cases), added precision (6 cases), or augmented spectrum (10 cases). In the latter subgroup, four novel fusion transcripts were found for which the clinical relevance remains unclear: NAB2::NCOA2, YAP1::NUTM2B, HSPA8::BRAF, and PDE2A::PLAG1. Overall, targeted RNA-seq has proven extremely valuable in the diagnostic workflow of soft tissue and bone tumours.
Identifiants
pubmed: 38738521
doi: 10.1002/2056-4538.12376
doi:
Substances chimiques
Biomarkers, Tumor
0
Oncogene Proteins, Fusion
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12376Subventions
Organisme : Universitaire Ziekenhuizen Leuven, KU Leuven
Informations de copyright
© 2024 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.
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