EKSPRESI ALPHA-THALASSEMIA/MENTAL RETARDATION X-LINKED (ATRX) PADA LOW GRADE GLIOMA DENGAN IDH MUTANT
Keywords:
glioma, ATRX, IDH, alpha-thalassemia/mental retardation X-linked, IDH mutantAbstract
Background: Gliomas are the most common malignancies of the central nervous system. Current glioma diagnosis relies on an integrated approach combining morphological and molecular features. Several molecular markers have been investigated to support glioma classification, including isocitrate dehydrogenase (IDH) and alpha-thalassemia/mental retardation X- linked (ATRX). IDH mutations are found in approximately 80% of gliomas, and around 70% of IDH-mutant gliomas are reported to be associated with ATRX mutations. Both IDH and ATRX alterations are involved in early gliomagenesis and are therefore more frequently observed in low-grade gliomas.
Objective: This study aimed to describe ATRX expression in low-grade gliomas with IDH mutation.
Methods: This retrospective study included 16 patients with low-grade glioma who underwent surgical resection at Dr. Sardjito Hospital. IDH mutation status was examined using the polymerase chain reaction (PCR) method. Histopathological diagnosis was established according to the WHO Classification of Tumours of the Central Nervous System 2021. ATRX status was assessed using immunohistochemical analysis. Clinical data, including sex, age, and tumor location, were also collected.
Results: Among the 16 patients, 56.25% were male, 75% were younger than 50 years, and frontal lobe involvement was observed in 50% of cases. All cases were classified as WHO grade 2 gliomas. Immunohistochemical analysis demonstrated ATRX retained expression in 68.75% of cases, while complete ATRX loss was observed in 31.25%. The predominance of ATRX retained expression in this cohort differs from several previous studies reporting higher frequencies of ATRX loss in low-grade gliomas. This finding suggests that gliomagenesis in a substantial proportion of cases may not involve the alternative lengthening of telomeres (ALT) pathway associated with ATRX mutation, but may proceed through other telomere maintenance mechanisms, reflecting molecular heterogeneity among IDH- mutant low-grade gliomas.
Conclusion: ATRX retained expression was more prevalent than ATRX loss in IDH-mutant low-grade gliomas in this study. These findings highlight the molecular heterogeneity of low-grade gliomas and support the importance of an integrated diagnostic approach. Further studies with larger sample sizes are needed to clarify the prognostic significance of ATRX expression in gliomas.
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Berkala Kesehatan Klinik, Vol. 19, No. 1, 2025: 11-20
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