Dataset Information

Automated Analysis of 1p/19q Status by FISH in Oligodendroglial Tumors: Rationale and Proposal of an Algorithm.

ABSTRACT:

Objective

To propose a new algorithm facilitating automated analysis of 1p and 19q status by FISH technique in oligodendroglial tumors with software packages available in the majority of institutions using this technique.

Methods

We documented all green/red (G/R) probe signal combinations in a retrospective series of 53 oligodendroglial tumors according to literature guidelines (Algorithm 1) and selected only the most significant combinations for a new algorithm (Algorithm 2). This second algorithm was then validated on a prospective internal series of 45 oligodendroglial tumors and on an external series of 36 gliomas.

Results

Algorithm 2 utilizes 24 G/R combinations which represent less than 40% of combinations observed with Algorithm 1. The new algorithm excludes some common G/R combinations (1/1, 3/2) and redefines the place of others (defining 1/2 as compatible with normal and 3/3, 4/4 and 5/5 as compatible with imbalanced chromosomal status). The new algorithm uses the combination + ratio method of signal probe analysis to give the best concordance between manual and automated analysis on samples of 100 tumor cells (91% concordance for 1p and 89% concordance for 19q) and full concordance on samples of 200 tumor cells. This highlights the value of automated analysis as a means to identify cases in which a larger number of tumor cells should be studied by manual analysis. Validation of this algorithm on a second series from another institution showed a satisfactory concordance (89%, κ = 0.8).

Conclusion

Our algorithm can be easily implemented on all existing FISH analysis software platforms and should facilitate multicentric evaluation and standardization of 1p/19q assessment in gliomas with reduction of the professional and technical time required.

SUBMITTER: Duval C

PROVIDER: S-EPMC4489714 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveTo study the feasibility and the diagnostic and prognostic interest of automated analysis of 1p, 19q, 9p and 10q status by FISH technique in oligodendroglial tumors.MethodsWe analyzed a retrospective series of 33 consecutive gliomas with oligodendroglial histology (originally diagnosed as 24 oligodendrogliomas and 9 oligoastrocytomas). For all cases, automated FISH analysis of 1p, 19q, 9p and 10q status were performed and compared to clinical and histological data, ATRX, IDH1R132H and alpha-internexin status (studied by immunohistochemistry) and overall survival (OS). Manual analysis of 9p and 10q status were also performed and compared to automated analysis to verify the concordance of the two methods.ResultsThe 33 gliomas were reclassified into 13 low-grade oligodendrogliomas (OII), 10 anaplastic oligodendrogliomas (OIII), 3 diffuse astrocytomas (AII), 3 anaplastic astrocytomas (AIII) and 4 glioblastomas (GBM) according to the WHO 2016 histological criteria. The 1p and/or 19q imbalanced status were restricted to astrocytomas with no correlation to their grade or their OS. Chromosome 9p deletion was restricted to OIII (70%) and GBM (100%) and was correlated with a shorter OS in the total cohort (p = 0.0007), the oligodendroglioma cohort (p = 0.03) and the astrocytoma cohort (p = 0.001). Concordance between 9p manual and automated analysis was satisfactory (81%, κ = 0.69). Chromosome 10q deletion was restricted to GBMs (50%) and was correlated with a poor OS in both the total cohort (p = 0.003) and the astrocytoma (AS) cohort (p = 0.04). Concordance between manual and automated analysis was satisfactory (79%, κ = 0.62).ConclusionAutomated analysis of 1p, 19q, 9p and 10q status by FISH is a reliable technique which allows for refined classification of oligodendroglial tumors. 1p and/or 19q imbalanced status is evidence of astrocytic differentiation. 9p deletion is found in high grade oligodendrogliomas and astrocytomas with a poor OS. 10q is related to GBM status and a poor OS.

Project description:The molecular genetic alterations of oligodendroglial tumors and mixed gliomas of the central nervous system were studied in a series of 37 cases (8 oligodendrogliomas, 13 anaplastic oligodendrogliomas, 8 oligoastrocytomas, and 8 anaplastic oligoastrocytomas). A total of 180 polymorphic loci and 5 nonpolymorphic gene loci, distributed over all chromosomes, were examined by restriction fragment length polymorphism analysis. Loss of heterozygosity was most frequently observed for loci on 19q with a commonly deleted region at 19q13.2-q13.4 distal to the CYP2a gene and proximal to the D19S22 locus. The incidence of allelic loss on 19q was particularly high (81%) in oligodendroglial tumors and equal to 31% in mixed gliomas. More than 75% of the tumors with allelic deletions on 19q also showed loss of heterozygosity for loci on 1p with one tumor showing only loss of alleles distal to the NGFB gene (1p13-pter). Seven (19%) tumors had lost alleles from 17p with the deleted region including the TP53 tumor suppressor gene in all cases. Sequencing of the TP53 transcripts from exons 2 to 10, however, did not reveal mutations of the remaining allele in any of these tumors. Anaplastic oligodendrogliomas and anaplastic oligoastrocytomas demonstrated an increased incidence of additional allelic losses involving most frequently chromosomes 9p and 10. Gene amplification was detected in two anaplastic tumors, affecting the epidermal growth factor receptor gene in both cases, with additional amplification of the renin gene at 1q32 in one of these cases. In total our results indicate both differences and similarities between the molecular genetic alterations in tumors with oligodendroglial and astrocytic differentiation. The loss of genetic information from 19q and 1p as well as the rarity of TP53 mutations in oligodendroglial tumors suggests that the early events in their oncogenesis are distinct from those associated with astrocytic tumors. However, similarities are indicated by the allelic losses on 9p and 10 in the anaplastic tumors, suggesting the utilization of common pathways of progression.

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