KJCAB, Volume 1, Issue 1, July 2021
Articles

A Review on the Methods for Identification of Mutations in the Tumour Suppressor Gene Retinoblastoma RB1

PDF
  • Kabilan G. Mariappan,
  • Manikandan Kathirvel,
  • Kannaki Pasupathi
Kabilan G. Mariappan
Department of Biotechnology, Alagappa University, Karaikudi, Tamilnadu
Manikandan Kathirvel
Department of Life Sciences, Kristu Jayanti College (Autonomous), Bengaluru, Karnataka
Kannaki Pasupathi
Department of Biotechnology, MGR University, Chennai, Tamilnadu
DOI: https://doi.org/10.59176/kjcab.v1i1.2169

Published 2021-07-26

Keywords

  • No Keywords.

How to Cite

Mariappan, K. G., Kathirvel, M. ., & Pasupathi, K. . (2021). A Review on the Methods for Identification of Mutations in the Tumour Suppressor Gene Retinoblastoma RB1. Kristu Jayanti Journal of Core and Applied Biology (KJCAB), 1(1), 28–32. https://doi.org/10.59176/kjcab.v1i1.2169
Crossref
Scopus
Google Scholar
Europe PMC

Abstract

Retinoblastoma is the most common intraocular cancer of childhood. RB1 is the gene responsible for causing retinoblastoma, spans more than 180 kilobases (kb) located on chromosome 13q14, which consist of 27 exons. Retinoblastoma in children may either be hereditary or non-hereditary. Mutations in RB1 gene are mostly point mutations of non-sense or missense type but could also be of frameshift type. These mutations can be identified from both blood and tumour samples by Sanger sequencing and other molecular identification techniques such as Multiplex Ligation-dependent Probe Amplification (MLPA). ‘Fragile’ codons are codons which gets point mutated to form stop codons so that the resulting protein will be incomplete or immature. In RB1, fragile codons get mutated predominantly and lead to the truncation of RB1 protein. The frequent mutations that predominantly occur in the arginine (CGA) codon, wherein changes in the single nucleotide results in the stop (UGA) codon, than any other fragile codon. The present paper reviews the role of RB1 mutations in retinoblastoma and the methods to identify it. We also make an attempt to identify the fragile codons in the RB genome based on the NCBI reference sequence NM_000321.2

PDF

Downloads

Download data is not yet available.

References

  1. Abraham A, Thirumalairaj K, Gaikwad N, Muthuk-karuppan V, Reddy AG, Thangaraj K, Kim U and Vanniarajan A (2019), Retinoblastoma dis-cordance in families with twins. Indian J Oph-thalmol. 67(3), 436-439. DOI: https://doi.org/10.4103/ijo.IJO_1245_18
  2. Abramson DH, Beaverson K, Sangani P, Vora RA, Lee TC, Hochberg HM and Ranjithan M (2003), Screening for retinoblastoma: presenting signs as prognosticators of patient and ocular surviv-al. Pediatrics. 112(6), 1248-1255. DOI: https://doi.org/10.1542/peds.112.6.1248
  3. Cusack BP, Arndt PF, Duret L and Crollius HR (2011), Preventing dangerous nonsense: selection for robustness to transcriptional error in human genes. PLoS Genet. 7(10), e1002276. DOI: https://doi.org/10.1371/journal.pgen.1002276
  4. Casci T. Molecular evolution: dealing with nonsense (2011), Nat Rev Genet. 12(12):805. DOI: https://doi.org/10.1038/nrg3109
  5. De Jong MC, Kors WA, de Graaf P, Castelijns JA, Kive-la T, and Moll AC (2014), Trilateral retinoblas-toma: a systematic review and meta-analysis. Lancet Oncol. 15(10), 1157-1167. DOI: https://doi.org/10.1016/S1470-2045(14)70336-5
  6. Gaikwad N, Vanniarajan A, Husain A, Jeyaram I, Thirumalairaj K, Santhi R and Kim U (2015), Knudson's hypothesis revisited in Indian reti-noblastoma patients. Asia Pac J Clin Oncol. 11(4), 299-307. DOI: https://doi.org/10.1111/ajco.12401
  7. Gargallo P, Oltra JS, Yanez Y, Segura V, Balaguer J, and Canete A (2018), Retinoblastoma: Towards an earlier diagnosis. Arch Soc Esp Oftalmol. 93(9), 439-443. DOI: https://doi.org/10.1016/j.oftale.2018.05.014
  8. Joseph B, Madhavan J, Mamatha G, Ramprasad VL, Gopal L and Kumaramanickavel G (2006), Reti-noblastoma: a diagnostic model for India. Asian Pac J Cancer Prev. 7(3), 485.
  9. Rao R, Honavar SG (2017), Retinoblastoma. Indian J Pediatr. 84(12):937-944. DOI: https://doi.org/10.1007/s12098-017-2395-0
  10. Richter S, Vandezande K, Chen N, Zhang K, Sutherland J, Anderson J and Gallie B (2003), Sensitive and efficient detection of RB1 gene mutations en-hances care for families with retinoblasto-ma. Am J Hum Genet. 72(2), 253-269. DOI: https://doi.org/10.1086/345651
  11. Rushlow DE, Mol BM, Kennett JY, Yee S, Pajovic S, Thériault BL, Prigoda-Lee NL, Spencer C, Di-maras H, Corson TW, Pang R, Massey C, God-bout R, Jiang Z, Zacksenhaus E, Paton K, Moll AC, Houdayer C, Raizis A, Halliday W, Lam WL, Boutros PC, Lohmann D, Dorsman JC and Gallie BL (2013), Characterisation of retinoblas-tomas without RB1 mutations: genomic, gene expression, and clinical studies. Lancet On-col. 14(4), 327-334. DOI: https://doi.org/10.1016/S1470-2045(13)70045-7
  12. Sambrook J and Russell DW (2006), Agarose gel elec-trophoresis. CSH Protoc. (1), pdb-prot4020. DOI: https://doi.org/10.1101/pdb.prot4020
  13. Sagi M, Frenkel A, Eilat A, Weinberg N, Frenkel S, Pe’er J, Abeliovich D and Lerer I (2015), Genet-ic screening in patients with Retinoblastoma in Israel. Fam Cancer. 14(3), 471-480. DOI: https://doi.org/10.1007/s10689-015-9794-z
  14. Skalet AH, Gombos DS, Gallie BL, Kim JW, Shields CL, Marr BP, Plon SE and Chévez-Barrios P (2018), Screening children at risk for retinoblas-toma: consensus report from the American As-sociation of Ophthalmic Oncologists and Pathologists. Ophthalmology, 125(3), 453-458. DOI: https://doi.org/10.1016/j.ophtha.2017.09.001
  15. Stuppia L, Antonucci I, Palka G and Gatta V (2012), Use of the MLPA assay in the molecular diagnosis of gene copy number alterations in human genetic diseases. Int J Mol Sci. 13(3), 3245-3276. DOI: https://doi.org/10.3390/ijms13033245
  16. Thirumalairaj K, Abraham A, Devarajan B, Gaikwad N, Kim U, Muthukkaruppan V and Vanniarajan A (2015), A stepwise strategy for rapid and cost-effective RB1 screening in Indian retinoblasto-ma patients. J Hum Genet. 60(9), 547-552. DOI: https://doi.org/10.1038/jhg.2015.62
  17. Tomar S, Sethi R, Sundar G, Quah TC, Quah BL and Lai PS (2017), Mutation spectrum of RB1 muta-tions in retinoblastoma cases from Singapore with implications for genetic management and counselling. PloS one, 12(6), e0178776. DOI: https://doi.org/10.1371/journal.pone.0178776
  18. Villegas VM, Hess DJ, Wildner A, Gold AS, Murray TG (2013), Retinoblastoma. Curr Opin Ophthalmol. 24(6):581. DOI: https://doi.org/10.1097/ICU.0000000000000002