Mohd Nizam Isa

Loss of heterozygosity on chromosomes 10q, 9p, 17p and 13q in Malays with malignant glioma

Abstract Recent advances in neuro-oncology have revealed different pathways of molecular oncogenesis in malignant gliomas including loss of heterozygosity on chromosomal regions harboring tumor suppressor genes. In the present study, we performed polymerase chain reaction–loss of heterozygosity (PCR-LOH) analysis using microsatellite markers to identify loss of heterozygosity on chromosomes 10q, 9p, 17p and 13q in the Malays with malignant gliomas. Of 12 cases with allelic losses, seven (58.3%) cases showed LOH on chromosome 10q, three (25.0%) cases showed LOH on chromosome 9p, four (33.3%) cases showed LOH on chromosome 17p and two (16.7%) cases showed LOH on chromosome 13q. The cases include five (41.7%) cases of glioblastoma multiforme, three (25.0%) cases of anaplastic astrocytoma, three (25.0%) cases of anaplastic oligodendroglioma and one (8.3%) case of anaplastic ependymoma. Four cases showed loss of heterozygosity on more than one locus. Our findings showed that loss of heterozygosity on specific chromosomal regions contributes to the molecular pathway of glioma progression in Malay population. In addition, these data provide useful evidence of molecular genetic alterations of malignant glioma in South East Asian patients, particularly in the East Coast of Malaysia.

Molecular Genetic Analysis of Anaplastic Pleomorphic Xanthoastrocytoma

A case of pleomorphic xanthoastrocytoma in a 10-year-old Malay boy is reported. The patient presented with headache and epilepsy. On computed tomography, a ring-enhancing low-density lesion was observed in the left fronto-temporal area. During surgery, a cystic tumour containing serous fluid was found and almost totally removed. Histologically, the tumour exhibited marked pleomorphism of oval and spindle-shaped cells intermixed with uni- and multinucleated giant cells, and xanthomatous cells with foamy cytoplasm. The tumour displayed pericellular reticulin and periodic acid-Schiff positive granules. Focally, six mitotic characters per 10 high-power fields were seen, and necrosis was confined only to the inner lining of the cyst. Mutational analysis showed that a frameshift mutation (a 4-bp deletion) in the p53 gene had occurred in codons 273 and 274 of exon 8. No mutation was detected in the p16 gene. No allelic loss and/or loss of heterozygosity were observed on chromosome 10 using microsatellite marker D105532. The patient was treated with postoperative radiotherapy because of histological anaplasia and the presence of residual tumour. The patient showed marked neurological recovery after a follow-up period of 2 years.

Association of p53 tumor suppressor gene with paraclinical and clinical modalities of gliomas patients in Malaysia

SummaryBackground. Alteration of the tumor suppressor gene p53 is considered to be a critical step in the development of human cancer. Changes in this gene have been detected in a wide range of human tumours, including gliomas. In glioma, the presence of p53 gene alterations has been associated with worse prognosis. Methods. Forty-seven Malaysian adult glioma patients of the Malay race were prospectively studied over a period of 3 years where the presence of p53 mutation using cold-SSCP method and their clinical and paraclinical response were correlated. Findings. Among these glioma patients, p53 mutations were detected in 12 tumors, an incidence rate of 25.5%. Mutations were found in 2 patients of grade II, and 5 patients both in grade III and grade IV. The sequencing results revealed the presence of base-substitutions (7) (58.3%) and frameshifts mutations (5) (41.7%). Of the base-substitutions, 57.1% were transversions and 42.9% were transitions. Interpretation. Our analysis shows that 3 factors were associated with p53 mutations i.e. grade, site and consistency of tumour using univariate analysis although multivariate analysis revealed no positive on predictors of mutation. In conclusion, although p53 genetic alterations are involved in glioma patients in Malaysia, it has no impact on prognosis.