Next-Generation Sequencing Panel for 1p/19q Codeletion and IDH1-IDH2 Mutational Analysis Uncovers Mistaken Overdiagnoses of 1p/19q Codeletion by FISH

• Published in: The Journal of molecular diagnostics : JMD Vol. 23; no. 9; pp. 1185 - 1194
• Main Authors: de Biase, Dario, Acquaviva, Giorgia, Visani, Michela, Marucci, Gianluca, De Leo, Antonio, Maloberti, Thais, Sanza, Viviana, Di Oto, Enrico, Franceschi, Enrico, Mura, Antonella, Ragazzi, Moira, Serra, Silvia, Froio, Elisabetta, Bisagni, Alessandra, Brandes, Alba A., Pession, Annalisa, Tallini, Giovanni
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2021
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Brain Neoplasms - genetics; Brain Neoplasms - pathology; Chromosomes, Human, Pair 1 - genetics; Chromosomes, Human, Pair 19 - genetics; Cohort Studies; Cost-Benefit Analysis; DNA Mutational Analysis - economics; DNA Mutational Analysis - methods; Female; Gene Deletion; Glioma - genetics; Glioma - pathology; High-Throughput Nucleotide Sequencing - economics; High-Throughput Nucleotide Sequencing - methods; Humans; In Situ Hybridization, Fluorescence - economics; In Situ Hybridization, Fluorescence - methods; Isocitrate Dehydrogenase - genetics; Male; Middle Aged; Molecular Diagnostic Techniques - economics; Molecular Diagnostic Techniques - methods; Overdiagnosis; Polymorphism, Single Nucleotide; Reproducibility of Results; Translocation, Genetic - genetics; Young Adult
• ISSN: 1525-1578; 1943-7811
• DOI: 10.1016/j.jmoldx.2021.06.004

The 1p/19q codeletion is the result of a translocation between chromosome 1 (Chr1p) and chromosome 19 (Chr19q) with the loss of derivative (1;19)(p10;q10) chromosome. The 1p/19q codeletion has predictive and prognostic significance, and it is essential for the classification of gliomas. In routine practice, the fluorescence in situ hybridization (FISH) diagnosis of 1p/19q codeletion is sometimes unexpected. This study aimed to develop a next-generation sequencing panel for the concurrent definition of the 1p/19q codeletion and IDH1/IDH2 mutation status to resolve these equivocal cases. A total of 65 glioma samples were investigated using a 1p/19q–single-nucleotide polymorphism (SNP)-IDH panel. The panel consists of 192 amplicons, including SNPs mapping to Chr1 and Chr19 and amplicons for IDH1/IDH2 analysis. The 1p/19q SNP-IDH panel consistently identified IDH1/IDH2 mutations. In 49 of 60 cases (81.7%), it provided the same 1p/19q results obtained by FISH. In the remaining 11 cases, the 1p/19q SNP-IDH panel uncovered partial chromosome imbalances as a result of interstitial amplification or deletion of the regions where the FISH probes map, leading to a mistaken overdiagnosis of 1p/19q codeletion by FISH. The 1p/19q SNP-IDH next-generation sequencing panel allows reliable analysis of the 1p/19q codeletion and IDH1/IDH2 mutation at the same time. The panel not only allows resolution of difficult cases but also represents a cost-effective alternative to standard molecular diagnostics procedures.