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CC BY 4.0 · Glob Med Genet 2021; 08(03): 116-122
DOI: 10.1055/s-0041-1731069
Original Article

Molecular Landscape for Malignant Transformation in Diffuse Astrocytoma

Thara Tunthanathip
1   Department of Surgery, Division of Neurosurgery, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand
,
Surasak Sangkhathat
2   Department of Surgery, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand
3   Department of Biomedical Sciences, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand
,
Kanet Kanjanapradit
4   Department of Pathology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand
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Abstract

Background Malignant transformation (MT) of low-grade gliomas changes dramatically the natural history to poor prognosis. Currently, factors associated with MT of gliomas have been inconclusive, in particular, diffuse astrocytoma (DA).

Objective The present study aimed to explore the molecular abnormalities related to MT in the same patients with different MT stages.

Methods Twelve specimens from five DA patients with MT were genotyped using next-generation sequencing (NGS) to identify somatic variants in different stages of MT. We used cross-tabulated categorical biological variables and compared the mean of continuous variables to assess for association with MT.

Results Ten samples succussed to perform NGS from one male and four females, with ages ranging from 28 to 58 years. The extent of resection was commonly a partial resection following postoperative temozolomide with radiotherapy in 25% of cases. For molecular findings, poly-T-nucleotide insertion in isocitrate dehydrogenase 1 (IDH1) was significantly related to MT as a dose–response relationship (Mann–Whitney's U test, p = 0.02). Also, mutations of KMT2C and GGT1 were frequently found in the present cohort, but those did not significantly differ between the two groups using Fisher's exact test.

Conclusion In summary, we identified a novel relationship between poly-T insertion polymorphisms that established the pathogenesis of MT in DA. A further study should be performed to confirm the molecular alteration with more patients.

Keywords

malignant transformation - diffuse astrocytoma - whole genome sequencing


Publication History

Article published online:
22 June 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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