1p/19q testing has no significance in the workup of glioblastomas.
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ABSTRACT: Aims
To determine whether testing for isolated 1p or 19q losses, or as a codeletion, has any significance in the workup of glioblastomas (GBMs).Methods
Upfront 1p/19q testing by fluorescence in situ hybridization (FISH) and/or polymerase chain reaction (PCR)-based loss of heterozygosity (LOH) was done in 491 gliomas that were histologically diagnosed as GBMs. Outcomes were determined and measured against 1p/19q results.Results
Twenty-eight showed apparent 1p/19q codeletion by either FISH and/or PCR-based LOH, but only 1/26 showed codeletion by both tests. Over 90% of tumours with apparent codeletion by either FISH or LOH also had 10q LOH and/or EGFR amplification, features inversely related to true whole-arm 1p/19q codeletion. Furthermore, only 1/28 tumours demonstrated an R132H IDH1 mutation. Neither 1p/19q codeletion by FISH nor LOH had an impact on GBM survival. Isolated losses of 1p or 19q also had no impact on survival.Conclusions
These data suggest that (i) 1p/19q testing is not useful on gliomas that are histologically GBMs; (ii) codeletion testing should be reserved only for cases with compatible morphology; and (iii) EGFR, 10q, and IDH1 testing can help act as safeguards against a false-positive 1p/19q result.
SUBMITTER: Clark KH
PROVIDER: S-EPMC4095883 | biostudies-literature | 2013 Oct
REPOSITORIES: biostudies-literature
Publications
1p/19q testing has no significance in the workup of glioblastomas.
Clark K H KH Villano J L JL Nikiforova M N MN Hamilton R L RL Horbinski C C
Neuropathology and applied neurobiology 20131001 6
<h4>Aims</h4>To determine whether testing for isolated 1p or 19q losses, or as a codeletion, has any significance in the workup of glioblastomas (GBMs).<h4>Methods</h4>Upfront 1p/19q testing by fluorescence in situ hybridization (FISH) and/or polymerase chain reaction (PCR)-based loss of heterozygosity (LOH) was done in 491 gliomas that were histologically diagnosed as GBMs. Outcomes were determined and measured against 1p/19q results.<h4>Results</h4>Twenty-eight showed apparent 1p/19q codeletio ...[more]
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Project description:Background: Chromosome 1p/19q codeletion is one of the most important genetic alterations for low grade gliomas (LGGs), and patients with 1p/19q codeletion have significantly prolonged survival compared to those without the codeletion. And the tumor immune microenvironment also plays a vital role in the tumor progression and prognosis. However, the effect of 1p/19q codeletion on the tumor immune microenvironment in LGGs is unclear. Methods: Immune cell infiltration of 281 LGGs from The Cancer Genome Atlas (TCGA) and 543 LGGs from the Chinese Glioma Genome Atlas (CGGA) were analyzed for immune cell infiltration through three bioinformatics tools: ESTIMATE algorithm, TIMER, and xCell. The infiltrating level of immune cells and expression of immune checkpoint genes were compared between different groups classified by 1p/19q codeletion and IDH (isocitrate dehydrogenase) mutation status. The differential biological processes and signaling pathways were evaluated through Gene Set Enrichment Analysis (GSEA). Correlations were analyzed using Spearman correlation. Results: 1p/19q codeletion was associated with immune-related biological processes in LGGs. The infiltrating level of multiple kinds of immune cells and expression of immune checkpoint genes were significantly lower in 1p/19q codeletion LGGs compared to 1p/19q non-codeletion cohorts. There are 127 immune-related genes on chromosome 1p or 19q, such as TGFB1, JAK1, and CSF1. The mRNA expression of these genes was positively correlated with their DNA copy number. These genes are distributed in multiple immune categories, such as chemokines/cytokines, TGF-β family members, and TNF family members, regulating immune cell infiltration and expression of the immune checkpoint genes in tumors. Conclusion: Our results indicated that 1p/19q codeletion status is closely associated with the immunosuppressive microenvironment in LGGs. LGGs with 1p/19q codeletion display less immune cell infiltration and lower expression of immune checkpoint genes than 1p/19q non-codeletion cases. Mechanistically, this may be, at least in part, due to the deletion of copy number of immune-related genes in LGGs with 1p/19q codeletion. Our findings may be relevant to investigate immune evasion in LGGs and contribute to the design of immunotherapeutic strategies for patients with LGGs.
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