Mal J Med Health Sci 16(2): 332-335, May 2020 332 Malaysian Journal of Medicine and Health Sciences (eISSN 2636-9346) CASE REPORT A Dual Genetic Alteration (Mitochondrial and Nuclear DNA): First Case in Malaysia Detected in Glioblastoma Multiforme Abdul Aziz Mohamed Yusoff, Wan Salihah Wan Abdullah, Alarmelu Nithya Ramanathan, Jafri Malin Abdullah, Zamzuri Idris Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia ABSTRACT Although the precise etiology of Glioblastoma multiforme (GBM, WHO grade IV) remains unknown, its progression is believed to be driven by the accumulation of multiple genetic alterations. Here, we report a case of a patient who developed GBM, and associated with dual alterations, particularly 4977-bp deletion in mtDNA (mtDNA 4977 ) and p.Arg132His (R132H) mutation in IDH1. A 35-year old Malaysian woman patient who primary diagnosed with as- trocytoma WHO grade I and subsequently after four years developed a GBM, was detected with a mtDNA 4977 . This deletion appears to be a sporadic mutation. Additionally, analysis of patient’s tumor tissue also found to harbor a het- erozygous IDH1 R132H mutation. This represents the first case report of coexisting mtDNA 4977 together with IDH1 R132H mutation in a Malaysian patient of GBM. The findings of dual alterations could be of therapeutic benefit if these alterations were justified to be contributing to GBM growth and aggressiveness. Keywords: Glioblastoma multiforme, 4977-bp mtDNA deletion, IDH1 (R132H) mutation, Double alteration Corresponding Author: Abdul Aziz Mohamed Yusoff, PhD Email: azizmdy@yahoo.com Tel: +609-7676164 INTRODUCTION Glioblastoma multiforme (GBM) is one of the most aggressive of adult brain malignancies and histopathologically classified into the highest grade IV astrocytoma and carries a worse prognosis. The progression of GBM involves the accumulation of various genetic alterations in proto-oncogenes and/or tumor suppressor genes that are encoded by the nuclear DNA (nDNA) (1). So far, the involvement of our second genome which is the mitochondrial genome (mtDNA) in GBM has not yet been fully elucidated and knowledge about its role on genetic pathways of GBM tumorigenesis is still limited. mtDNA is sensitive to oxidative stress-linked damage. Impaired mitochondrial stability caused by mtDNA alterations is expected to lead to a loss of mitochondrial energy production efficiency and an enhanced production of ROS. These processes may promote to uncontrolled cell growth, proliferation and eventually cancer. Various type of mtDNA alterations are suspected to be associated with human carcinogenesis (2). mtDNA alteration such as the 4977-bp large-scale deletion (mtDNA 4977 ), recognized as “common deletion”, has been detected in various types of cancers (3). To date, mtDNA 4977 in GBM has never been reported. In the present study, we describe a case of the coexistence of mtDNA 4977 and IDH1 R132H mutation in a Malaysian GBM patient. Informed consent form was signed by patient, and research protocol was approved by the institutional ethical committee (IRB Reg. No: 00004494). CASE REPORT We report a case of a 35-year-old lady (patient B5) who presented with late onset epilepsy with intermittent right parietal headaches. Examination reported no neurological deficits. MRI brain revealed a large solid mass in the right frontal parasagittal region (2.9cm x 5.8cm x 5cm) with perilesional edema. The mass was hypointense on T1WI and hyperintense on T2WI and had no contrast enhancement but shows small cystic areas within it. She then underwent a tumor biopsy and the histopathology revealed astrocytoma Grade I (Figure 1A). She was subsequently managed conservatively with follow-up MRI. However, four years following surgery, she developed progressive lower limb and upper limb weakness. She also demonstrated personality changes with emotional lability, memory impairment and speech disturbances.