A STUDY OF THE GENETIC VARIATIONS IN N-TERMINUS, C-TERMINUS AND PROMOTER OF RB1 GENE AMONG RETINOBLASTOMA PATIENTS IN MALAYSIA
| dc.contributor.author | SITI NORULHUDA, HAJI DRAMAN@HASHIM | |
| dc.date.accessioned | 2017-11-01T02:26:05Z | |
| dc.date.available | 2017-11-01T02:26:05Z | |
| dc.date.issued | 2012-05 | |
| dc.description.abstract | Retinoblastoma (RB) is the most common primary intraocular tumor affecting mainly children under five years of age, with a prevalence of 1 in 15 000 to 20 000 live births. Retinoblastoma is divided into hereditary and sporadic types. It is caused by mutations or changes in RB1 gene, a tumor suppressor gene. The aim of this study is to detect mutations in N-terminus, C-terminus and promoter region of RB1 gene in retinoblastoma patients in Malaysia, as well as its association with staging and laterality of the patients. A total of 68 children with sporadic RB from Hospital Universiti Sains Malaysia (HUSM), Hospital Kuala Lumpur (HKL) and University Malaya Medical Centre (UMMC) and 68 healthy ethnic-matched controls were recruited. Venesection was done and 3cc of blood was taken. Tumor tissue samples were also collected from four patients. A total of 200μl DNA was extracted using commercially available extraction kit. PCR was conducted using self-designed primers for exons in N-terminus and C-terminus with its intronic flanking region, and promoter region of RB1 gene. Screening for mutations or polymorphisms for Nterminus was conducted using DHPLC analysis and direct sequence was done for Cterminus and promoter region. Male to female patient ratio was 2:1, where 79% were Malays, 12% Chinese and 9% Indian. Majority of our patients presented with leukocoria and unilateral involvement with no predilection to right or left eye. The mean age at diagnosis of patients was 23.42 (17.64) months. There was statistical significant difference between age of diagnosis and laterality of the disease (p=0.011). Bilateral RB was diagnosed earlier [17.68 (18.33) months) than unilateral RB [28.65 (15.46) months). There was also significant association between laterality and racial group of RB patients (p=0.025). Two nonsense mutations and four SNPs were detected in N-terminus; one SNP was detected in the promoter region. However, C-terminus was devoid of any polymorphism or mutation. All mutations and polymorphisms which were found in 30 patients and healthy controls involved a heterozygous type of single nucleotide substitution. The nonsense mutations; Arg320X and Glu323X were detected in 3 children with RB. A novel SNP; IVS1- 3T>G found in this study was identified in one patient. IVS4-77G>A identified in four patients was found to significantly increase the susceptibility to develop RB (p=0.044). However, there was no significant association between identified mutations and polymorphisms with laterality and staging of RB. There was no disparity in mutations and polymorphism between peripheral blood leukocytes and available tumor tissue. We postulate that SNP IVS4-77G>A might play a role in the predisposition to retinoblastoma. The other five SNPs are most likely important as genetic variant markers for population studies. However, a larger sample size is needed for further confirmation. | en_US |
| dc.identifier.uri | http://hdl.handle.net/123456789/5203 | |
| dc.language.iso | en | en_US |
| dc.publisher | Pusat Pengajian Sains Perubatan Universiti Sains Malaysia | en_US |
| dc.subject | Human Genetics | en_US |
| dc.title | A STUDY OF THE GENETIC VARIATIONS IN N-TERMINUS, C-TERMINUS AND PROMOTER OF RB1 GENE AMONG RETINOBLASTOMA PATIENTS IN MALAYSIA | en_US |
| dc.type | Thesis | en_US |
Files
License bundle
1 - 1 of 1
Loading...
- Name:
- license.txt
- Size:
- 1.71 KB
- Format:
- Item-specific license agreed upon to submission
- Description: