LOGGIC Core BioClinical Data Bank: Added clinical value of RNA-Seq in an international molecular diagnostic registry for pediatric low-grade glioma patients.
RNA sequencing
actionable drivers
molecular profiling
pLGG
rare gene fusions
Journal
Neuro-oncology
ISSN: 1523-5866
Titre abrégé: Neuro Oncol
Pays: England
ID NLM: 100887420
Informations de publication
Date de publication:
02 11 2023
02 11 2023
Historique:
medline:
8
11
2023
pubmed:
20
4
2023
entrez:
19
04
2023
Statut:
ppublish
Résumé
The international, multicenter registry LOGGIC Core BioClinical Data Bank aims to enhance the understanding of tumor biology in pediatric low-grade glioma (pLGG) and provide clinical and molecular data to support treatment decisions and interventional trial participation. Hence, the question arises whether implementation of RNA sequencing (RNA-Seq) using fresh frozen (FrFr) tumor tissue in addition to gene panel and DNA methylation analysis improves diagnostic accuracy and provides additional clinical benefit. Analysis of patients aged 0 to 21 years, enrolled in Germany between April 2019 and February 2021, and for whom FrFr tissue was available. Central reference histopathology, immunohistochemistry, 850k DNA methylation analysis, gene panel sequencing, and RNA-Seq were performed. FrFr tissue was available in 178/379 enrolled cases. RNA-Seq was performed on 125 of these samples. We confirmed KIAA1549::BRAF-fusion (n = 71), BRAF V600E-mutation (n = 12), and alterations in FGFR1 (n = 14) as the most frequent alterations, among other common molecular drivers (n = 12). N = 16 cases (13%) presented rare gene fusions (eg, TPM3::NTRK1, EWSR1::VGLL1, SH3PXD2A::HTRA1, PDGFB::LRP1, GOPC::ROS1). In n = 27 cases (22%), RNA-Seq detected a driver alteration not otherwise identified (22/27 actionable). The rate of driver alteration detection was hereby increased from 75% to 97%. Furthermore, FGFR1 internal tandem duplications (n = 6) were only detected by RNA-Seq using current bioinformatics pipelines, leading to a change in analysis protocols. The addition of RNA-Seq to current diagnostic methods improves diagnostic accuracy, making precision oncology treatments (MEKi/RAFi/ERKi/NTRKi/FGFRi/ROSi) more accessible. We propose to include RNA-Seq as part of routine diagnostics for all pLGG patients, especially when no common pLGG alteration was identified.
Sections du résumé
BACKGROUND
The international, multicenter registry LOGGIC Core BioClinical Data Bank aims to enhance the understanding of tumor biology in pediatric low-grade glioma (pLGG) and provide clinical and molecular data to support treatment decisions and interventional trial participation. Hence, the question arises whether implementation of RNA sequencing (RNA-Seq) using fresh frozen (FrFr) tumor tissue in addition to gene panel and DNA methylation analysis improves diagnostic accuracy and provides additional clinical benefit.
METHODS
Analysis of patients aged 0 to 21 years, enrolled in Germany between April 2019 and February 2021, and for whom FrFr tissue was available. Central reference histopathology, immunohistochemistry, 850k DNA methylation analysis, gene panel sequencing, and RNA-Seq were performed.
RESULTS
FrFr tissue was available in 178/379 enrolled cases. RNA-Seq was performed on 125 of these samples. We confirmed KIAA1549::BRAF-fusion (n = 71), BRAF V600E-mutation (n = 12), and alterations in FGFR1 (n = 14) as the most frequent alterations, among other common molecular drivers (n = 12). N = 16 cases (13%) presented rare gene fusions (eg, TPM3::NTRK1, EWSR1::VGLL1, SH3PXD2A::HTRA1, PDGFB::LRP1, GOPC::ROS1). In n = 27 cases (22%), RNA-Seq detected a driver alteration not otherwise identified (22/27 actionable). The rate of driver alteration detection was hereby increased from 75% to 97%. Furthermore, FGFR1 internal tandem duplications (n = 6) were only detected by RNA-Seq using current bioinformatics pipelines, leading to a change in analysis protocols.
CONCLUSIONS
The addition of RNA-Seq to current diagnostic methods improves diagnostic accuracy, making precision oncology treatments (MEKi/RAFi/ERKi/NTRKi/FGFRi/ROSi) more accessible. We propose to include RNA-Seq as part of routine diagnostics for all pLGG patients, especially when no common pLGG alteration was identified.
Identifiants
pubmed: 37075810
pii: 7131410
doi: 10.1093/neuonc/noad078
pmc: PMC10628936
doi:
Substances chimiques
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
Protein-Tyrosine Kinases
EC 2.7.10.1
Proto-Oncogene Proteins
0
VGLL1 protein, human
0
DNA-Binding Proteins
0
Transcription Factors
0
Banques de données
GEO
['GSE228100']
Types de publication
Multicenter Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2087-2097Subventions
Organisme : Brain Tumour Charity
Organisme : Pediatric Brain Tumor Foundation
ID : HIT-LOGGIC
Organisme : Deutsche Kinderkrebsstiftung
Commentaires et corrections
Type : CommentIn
Informations de copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Références
Acta Neuropathol. 2021 Apr;141(4):605-617
pubmed: 33585982
Klin Padiatr. 2019 May;231(3):107-135
pubmed: 31108561
J Cancer. 2019 Oct 17;10(25):6314-6326
pubmed: 31772664
Nat Genet. 2013 Jun;45(6):602-12
pubmed: 23583981
Pediatr Blood Cancer. 2014 Jul;61(7):1173-9
pubmed: 24482038
Nat Commun. 2015 Dec 09;6:10001
pubmed: 26647970
J Clin Oncol. 2017 Jul 20;35(21):2370-2377
pubmed: 28640698
Nature. 2018 Mar 22;555(7697):469-474
pubmed: 29539639
J Neuropathol Exp Neurol. 2008 Mar;67(3):240-9
pubmed: 18344915
Clin Cancer Res. 2019 Mar 15;25(6):1851-1866
pubmed: 30530705
JCO Precis Oncol. 2022 Jan;6:e2000504
pubmed: 35085008
Cancer Cell. 2020 Apr 13;37(4):569-583.e5
pubmed: 32289278
Curr Opin Pediatr. 2019 Feb;31(1):21-27
pubmed: 30531227
Cancer Cell. 2020 Apr 13;37(4):424-425
pubmed: 32289265
Neuro Oncol. 2022 Sep 6;24(Suppl 3):iii1-iii38
pubmed: 36066969
Acta Neuropathol. 2016 Jun;131(6):833-45
pubmed: 26810070
PLoS Comput Biol. 2011 May;7(5):e1001138
pubmed: 21625565
Neuropathol Appl Neurobiol. 2021 Apr;47(3):406-414
pubmed: 33336421
J Clin Invest. 2008 May;118(5):1739-49
pubmed: 18398503
Cancer Discov. 2021 Nov;11(11):2764-2779
pubmed: 34373263
Cancer Res. 2008 Nov 1;68(21):8673-7
pubmed: 18974108
Int J Cancer. 2020 Dec 15;147(12):3471-3489
pubmed: 32580249
Nat Genet. 2013 Aug;45(8):927-32
pubmed: 23817572
Neuro Oncol. 2017 Jun 1;19(6):750-761
pubmed: 27683733
Acta Neuropathol. 2020 Aug;140(2):237-239
pubmed: 32476062
Neuro Oncol. 2023 Apr 6;25(4):735-747
pubmed: 35977048
Eur J Cancer. 2022 Dec;177:120-142
pubmed: 36335782
Acta Neuropathol. 2019 Nov;138(5):827-835
pubmed: 31278449
Neuro Oncol. 2021 Aug 2;23(8):1231-1251
pubmed: 34185076
Neuropediatrics. 2016 Apr;47(2):70-83
pubmed: 26764564
Neuro Oncol. 2011 Feb;13(2):223-34
pubmed: 21177781
Eur J Cancer. 2017 Aug;81:206-225
pubmed: 28649001