Single nCounter assay for prediction of MYCN amplification and molecular classification of medulloblastomas: a multicentric study.

Autor: Moreno DA; Molecular Oncology Research Center Dr. Paulo Prata, Barretos Cancer Hospital, Barretos, Brazil., da Silva LS; Molecular Oncology Research Center Dr. Paulo Prata, Barretos Cancer Hospital, Barretos, Brazil., Zanon MF; Molecular Diagnosis Laboratory Dr. Paulo Prata, Barretos Cancer Hospital, Barretos, Brazil., Bonatelli M; Molecular Diagnosis Laboratory Dr. Paulo Prata, Barretos Cancer Hospital, Barretos, Brazil., de Paula FE; Molecular Diagnosis Laboratory Dr. Paulo Prata, Barretos Cancer Hospital, Barretos, Brazil., de Medeiros Matsushita M; Pathology Department Dr. Paulo Prata, Barretos Cancer Hospital, Barretos, Brazil., Teixeira GR; Pathology Department Dr. Paulo Prata, Barretos Cancer Hospital, Barretos, Brazil.; Barretos School of Health Sciences Dr. Paulo Prata, Barretos Cancer Hospital, Barretos, Brazil., Santana IVV; Pathology Department Dr. Paulo Prata, Barretos Cancer Hospital, Barretos, Brazil., Saggioro F; Department of Pathology and Forensic Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Neder L; Department of Pathology and Forensic Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Stavale JN; Federal University of São Paulo (UNIFESP), São Paulo, Brazil., Malheiros SMF; Federal University of São Paulo (UNIFESP), São Paulo, Brazil., Lima M; AC Camargo Hospital, São Paulo, Brazil., Hajj GNM; AC Camargo Hospital, São Paulo, Brazil., Garcia-Rivello H; Pathology Department, Italian Hospital of Buenos Aires, Buenos Aires, Argentina., Christiansen S; Pathology Department, Italian Hospital of Buenos Aires, Buenos Aires, Argentina., Nunes S; Pediatric Oncology Department, Hospital São João, Porto, Portugal., da Costa MJG; Pediatric Oncology Department, Hospital São João, Porto, Portugal., Soares MJ; Clinical Hematology Department, Hospital São João, Porto, Portugal., Pinheiro J; Department of Pathology, Hospital São João, Porto, Portugal., Junior CA; Pediatric Oncology Department, Pediatric Neurosurgery Department, Barretos Cancer Hospital, Barretos, Brazil., Mançano BM; Molecular Oncology Research Center Dr. Paulo Prata, Barretos Cancer Hospital, Barretos, Brazil.; Pediatric Oncology Department, Pediatric Neurosurgery Department, Barretos Cancer Hospital, Barretos, Brazil., Reis RM; Molecular Oncology Research Center Dr. Paulo Prata, Barretos Cancer Hospital, Barretos, Brazil. ruireis.hcb@gmail.com.; Molecular Diagnosis Laboratory Dr. Paulo Prata, Barretos Cancer Hospital, Barretos, Brazil. ruireis.hcb@gmail.com.; ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal. ruireis.hcb@gmail.com.; School of Medicine, Life and Health Sciences Research Institute (ICVS), University of Minho, Braga, Portugal. ruireis.hcb@gmail.com.
Jazyk: angličtina
Zdroj: Journal of neuro-oncology [J Neurooncol] 2022 Mar; Vol. 157 (1), pp. 27-35. Date of Electronic Publication: 2022 Feb 15.
DOI: 10.1007/s11060-022-03965-1
Abstrakt: Purpose: Medulloblastoma is the most frequent pediatric malignant brain tumor, and is divided into four main subgroups: WNT, SHH, group 3, and group 4. MYCN amplification is an important medulloblastoma prognostic biomarker. We aimed to molecular classify and predict MYCN amplification in a single assay.
Methods: It was included 209 medulloblastomas from 205 patients (Brazil, Argentina, and Portugal), divided into training (n = 50) and validation (n = 159) sets. A nCounter assay was carried out using a custom panel for molecular classification, with additional genes, including MYCN. nSolver 4.0 software and the R environment were used for profiling and MYCN mRNA analysis. MYCN amplification by FISH was performed in 64 cases.
Results: The 205 medulloblastomas were classified in SHH (44.9%), WNT (15.6%), group 3 (18.1%) and group 4 (21.4%). In the training set, MYCN amplification was detected in three SHH medulloblastomas by FISH, which showed significantly higher MYCN mRNA counts than non-FISH amplified cases, and a cutoff for MYCN amplification was established ([Formula: see text] + 4σ = 11,124.3). Applying this threshold value in the validation set, we identified MYCN mRNA counts above the cutoff in three cases, which were FISH validated.
Conclusion: We successfully stratified medulloblastoma molecular subgroups and predicted MYCN amplification using a single nCounter assay without the requirement of additional biological tissue, costs, or bench time.
(© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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