Article type: Research Article
Authors: Macías, M.a; b; 1 | Dean, M.c | Atkinson, A.c | Jiménez-Morales, S.d | García-Vazquez, F.J.e | Saldaña-Alvarez, Y.d | Ramírez-Bello, J.d | Chávez, M.a | Orozco, L.d; *
Affiliations: [a] Clinical Research Laboratory, National Institute of Paediatrics, Mexico City, Mexico | [b] PhD Program in Biomedical Sciences, UNAM, Mexico City, Mexico | [c] National Cancer Institute, NIH Frederick, MD, USA | [d] Laboratory of Genomic of Complex Diseases, National Institute of Genomics Medicine, Mexico City, Mexico | [e] Pathology Department, National Institute of Pediatrics, Mexico City, Mexico
Correspondence:
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Corresponding author: Dr. L. Orozco, Investigación, Instituto Nacional de Medicina Genómica, Periférico Sur 4124, Torre Zafiro II, 6 piso, Col. Jardines del Pedregal, Mexico City, Mexico, CP 01900. E-mail: [email protected]; [email protected].
Note: [1] This work was submitted in partial fulfilment of the requirements for the PhD degree at Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México.
Abstract: RB1 mutation detection has greatly improved the clinical management of retinoblastoma and provides critical information to predict the risk of inheriting the disease. We screened for RB1 gene sequence alterations in both peripheral blood and tumor specimens from a total of 48 Mexican retinoblastoma patients using an SSCP-based screening approach followed by sequencing. Overall, 21 (43.8%) cases were bilateral and 27 (56.2%) were unilateral. Interestingly, 51.8% of unilateral patients developed the tumor before age 1 year and 10 of wich (71.4%) were diagnosed before the age of 6 months. Thirteen different oncogenic mutations were detected in 14/48 (29.2%) patients, 9 of which were germline (64.3%). Six of these mutations are novel (IVS3-1G>T, 125X, 389X, 610X, 750X and −149G>T). The most frequent types of mutation were frameshift and nonsense (30.8% each). Moreover, 5 intronic variants were identified, two of which are novel (g.41908 C/A and g.161976del6T). Loss of heterozygosity of the RB1 gene as assessed by intron1/BamHI and intron17/XbaI intragenic markers was 50.0% (18 of 36 informative cases), being higher in tumors with known mutations (76.9% vs 34.8%). This low mutation detection rate and the earlier age at diagnosis in unilateral retinoblastoma cases suggest that other RB1 inactivating mechanisms could be present in the retinoblastoma development. In this study, mutation analysis was not helpful to distinguish sporadic and hereditary retinoblastoma, so, other approaches are needed to improve the molecular diagnosis of retinoblastoma and supports further investigations of Mexican retinoblastoma patients.
Keywords: Retinoblastoma, RB1 gene, mutations, loss of heterozygosity, Mexican patients
DOI: 10.3233/CBM-2008-4205
Journal: Cancer Biomarkers, vol. 4, no. 2, pp. 93-99, 2008
