Mutational Analysis in N- and C- Termini of RB1 Gene among Sporadic Retinoblastoma Patients in Malaysia

作者：Hashim Siti Norulhuda; Hanafi Hanani; Ishak Siti Raihan; Rahmat Jamalia; Nasir Ariffin; Ismail Shatriah; Khaliddin Nurliza; Alwi Zilfalil; Tajudin Liza Sharmini Ahmad^*

来源：International Medical Journal, 2012, 19(4): 369-372.

• retinoblastoma
• RB1
• N-terminus
• C-terminus
• mutation
• SNP
• Malaysian

Objectives: To detect mutations and single nucleotide polymorphisms (SNPs) in N- and C-termini of RB1 and to determine the association of these genetic variations with laterality and staging of retinoblastoma in Malaysian children with RB. %26lt;br%26gt;Methods: Peripheral blood leukocytes were collected from 66 retinoblastoma patients and 66 healthy volunteers. Tumor tissue specimen was also collected from three available patients. The DNA was extracted using commercially available extraction kit. PCR were conducted using self-designed primers. The mutational analysis was performed using DHPLC and direct sequencing. %26lt;br%26gt;Results: Two nonsense mutations and four SNPs were detected in N-terminus, but none in C-terminus. The non-sense mutations; Arg320X and GIu323X were detected in 3 children with RB. A novel SNP; IVS1-3T %26gt; G was also identified in this study. There was a significant difference in allele frequency of IVS4-77G %26gt; A between patients and healthy control group (p = 0.044). There was no significant association between polymorphisms with laterality and staging of RB. %26lt;br%26gt;Conclusion: Arg320X and GIu323X may play an important role in the pathogenesis of RB. SNP IVS4-77G %26gt; A is a potential genetic marker for susceptibility to RB in our population.

• 出版日期2012-12