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Molecular-genetic characterisation of gliomas that recur as same grade or higher grade tumours

¹ Department of Human Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
² Department of Neuropathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
³ Department of Neurosurgery, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands

Correspondence to:
Correspondence to:
Dr T J M Hulsebos
Institute of Human Genetics, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, the Netherlands; t.j.hulsebos{at}amc.uva.nl

Background: Due to their invasive growth, gliomas usually cannot be removed completely and almost always recur as same grade or higher grade malignancies.

Objective: To determine whether there were differences in the accumulation of genetic changes between the two types of glioma recurrence.

Methods: We genetically characterised 14 cases of lower grade glioma with a same grade recurrence, 12 cases of glioblastoma recurrence, and 14 cases of lower grade glioma with a higher grade recurrence. We investigated LOH (loss of heterozygosity) at 1p36, 10p15, the PTEN region in 10q23, the DMBT1 region in 10q25, 19q13, 22q13, LOH and mutation of TP53, and EGFR amplification.

Results: Genetic heterogeneity in the primary tumour was inferred in 3 cases of lower grade glioma with a higher grade recurrence. The cases of lower grade glioma with a higher grade recurrence displayed increased genetic instability in the recurrence (mean of 2.0 additional genetic changes per case) compared to cases with a same lower grade recurrence or those with a glioblastoma recurrence (mean of 0.6 and 0.8 additional changes per case, respectively). Compared to unselected primary glioblastomas, the glioblastomas that recurred as an operable tumour had infrequent EGFR amplification (8% v 30–40% of cases).

Conclusions: Gliomas recurring as higher grade lesions might be genetically heterogeneous and accumulate more genetic changes than gliomas recurring as same grade lesions (whether originally low or high grade). Primary glioblastomas from patients for which the recurrence is operated because of prognostically more favourable clinical indices have infrequent EGFR amplification.

Abbreviations: LOH, loss of heterozygosity

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