Detailed Characterization of Alterations of Chromosomes 7, 9, and 10 in Glioblastomas as Assessed by Single-Nucleotide Polymorphism Arrays

Crespo, Inês; Vital, Ana Luísa; Nieto, Ana Belén; Rebelo, Olinda; Tão, Hermínio; Lopes, María Celeste; Oliveira, Catarina R.; French, Pim J.; Órfão, Alberto; Tabernero, María Dolores

doi:10.1016/j.jmoldx.2011.06.003

Cited by 59 publications

(54 citation statements)

References 72 publications

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“…We report that MTAP expression is retained in the majority of PAs. The few studies that have analyzed MTAP in gliomas reported MTAP deletions and reduced mRNA expression in pediatric [38] and adult glioblastomas [36,37,40,44] . We also observed reduced MTAP tumor expression in a small number of infiltrative diffuse astrocytomas (i.e.…”

Section: Discussionmentioning

confidence: 99%

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Expression of Methylthioadenosine Phosphorylase (MTAP) in Pilocytic Astrocytomas

et al. 2015

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Background/Objectives: Pilocytic astrocytomas (PAs) are the most frequent astrocytomas in children and adolescents. Methilthioadenosine phosphorylase(MTAP) is a tumor-suppressor gene, the loss of expression of which is associated with a poor prognosis and better response to specific chemotherapy in leukemia and non-small-cell lung cancer. The expression of MTAP in brain tumors remains largely unknown and its biological role in PA is still unexplored. Our aims were to describe the immunohistochemical MTAP expression in a series of PAs and relate it to the clinicopathological features of the patients. Methods: We assessed MTAP expression on immunohistochemistry in 69 pediatric and adult patients with PA in a tissue microarray platform. Results: Retained expression of MTAP was seen in >85% of the tumors compared to in the nonneoplastic adjacent tissue. Only 3 supratentorial tumors showed a complete loss of MTAP expression. No significant association with clinicopathological features or overall survival of the patients was found. Conclusions: MTAP expression is retained in PAs and is not an outcome predictor for these tumors. Nevertheless, a subset of patients with PAs exhibiting a loss of MTAP could potentially benefit from treatment with specific chemotherapy, especially when lesions are recurrent or surgical resection is not recommended.

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Section: Discussionmentioning

confidence: 99%

“…in the lung, liver and breast [30,[33][34][35] . In tumors of the central nervous system, deletion and gene copy-number breakpoints of MTAP have been reported in glioblastomas [36,37] , and in pediatric high-grade gliomas [38] , respectively. However, none of these studies assessed MTAP expression by immunohistochemistry.…”

Section: Introductionmentioning

confidence: 99%

Expression of Methylthioadenosine Phosphorylase (MTAP) in Pilocytic Astrocytomas

et al. 2015

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“…Primary and secondary GBMs are histologically indistinguishable, yet they evolve from different genetic precursors and show distinctive genetic alterations that can allow for differentiation (42, 43) ( Table 1). The alterations seen most frequently in primary GBM are EGFR amplification or mutation, PTEN deletion or mutation, and CDKN2A-p16 INK4a deletion (44). Amplification or mutation of EGFR results in constitutive activity, increased proliferation, and survival of mutated cells.…”

Section: Classification Of Glioblastoma Based On Genetic Markers Genomentioning

confidence: 99%

Glioblastoma Genomics: A Very Complicated Story

Lombardi

Assem

2017

Glioblastoma

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Glioblastoma is a deadly disease that has not shown improvement despite the development of new diagnostic tools and innovative targeted therapies. This grim outcome is mainly related to a complex intra-and inter-individual heterogeneity resulting from severe genetic instability. Understanding glioblastoma biology may establish a foundation to improve prophylaxis, early diagnosis, prognosis, and treatment prediction, thus leading to a better outcome. Recent advances in technologies such as genomics, epigenomics, transcriptomics, and proteomics have led to unprecedented discoveries of potential prognostic and predictive markers. Several of these biomarkers are in deep need of validation to be used in clinical routine. In this chapter, we will discuss the most accomplished recent advances in the genomics of glioblastoma and insight into personalized medicine using validated, and not yet validated, biomarkers that may have great potential to improve patients' outcomes.

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“…Chromosome arm 10q deletion has long been known to be common in high grade gliomas [39] and especially to GBMs [40,41]. Several tumor suppressors including PTEN have been identified on this arm.…”

Section: Discussionmentioning

confidence: 99%

Contribution of 1p, 19q, 9p and 10q Automated Analysis by FISH to the Diagnosis and Prognosis of Oligodendroglial Tumors According to WHO 2016 Guidelines

Michaud¹,

Tayrac²,

D’Astous³

et al. 2016

PLoS ONE

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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.

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Detailed Characterization of Alterations of Chromosomes 7, 9, and 10 in Glioblastomas as Assessed by Single-Nucleotide Polymorphism Arrays

Cited by 59 publications

References 72 publications

Expression of Methylthioadenosine Phosphorylase (MTAP) in Pilocytic Astrocytomas

Expression of Methylthioadenosine Phosphorylase (MTAP) in Pilocytic Astrocytomas

Glioblastoma Genomics: A Very Complicated Story

Contribution of 1p, 19q, 9p and 10q Automated Analysis by FISH to the Diagnosis and Prognosis of Oligodendroglial Tumors According to WHO 2016 Guidelines

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