RESUMEN
PurposeThe most common intraocular tumor in childhood, retinoblastoma, is largely associated with mutations in the RB1 gene. In the most comprehensive RB1 screening in Iran, we evaluated the RB1 mutations in 106 patients with retinoblastoma, including 73 bilateral (heritable) and 33 unilateral (sporadic) cases.Patients and methodsMutations were identified using amplification refractory mutation system (ARMS) PCR and direct sequencing of the 27 coding exons of RB1 and multiplex ligation-dependent probe amplification (MLPA).Results and ConclusionWe found 33 (31%) and 64 (60%) patients with sporadic unilateral and bilateral retinoblastoma, respectively as well as 9 (8.5%) cases with hereditary bilateral retinoblastoma. In total, we identified 52 causative RB1 mutations in 106 patients (global mutation rate of 49%). Of the 52 patients, 48 (92%) had sporadic and familial bilateral and 4 (8%) had sporadic unilateral RB. Therefore, the detection rate of RB1 mutations was 66% (48/73) and 12% (4/33) in bilateral and unilateral cases, respectively. Mutations were classified as nonsense in 31 (60%), missense in 1 (2%), large deletion in 11 (21%), small deletion in the 7 novel (15%) and splice site mutation in 2 (4%) patients with RB. Of 31 nonsense mutations, 23 (74%) occurred in the 11 Arginine codons of the RB1. Seven mutations (13%) were novel, and 45 (87%) had been previously reported. Thirty-three mutations were single-base substitutions leading to 31 nonsense amino acid changes and 2 splice site mutations in introns 12 and 16 of RB1. The altered 3D model structures of the RB1 novel mutant proteins are also predicted in this study.
Asunto(s)
Pueblo Asiatico/genética , Codón sin Sentido/genética , Predisposición Genética a la Enfermedad/genética , Pruebas Genéticas , Neoplasias de la Retina/genética , Retinoblastoma/genética , Niño , Preescolar , Análisis Mutacional de ADN , Femenino , Expresión Génica , Humanos , Lactante , Irán/epidemiología , Masculino , Datos de Secuencia Molecular , Retina/patología , Neoplasias de la Retina/epidemiología , Neoplasias de la Retina/patología , Retinoblastoma/epidemiología , Retinoblastoma/patologíaRESUMEN
Ahead of Print article withdrawn by publisher.
RESUMEN
We report a girl with a history of Ph(-) pre-B-ALL and three years of disease-free survival admitting to our hospital for regular end of treatment checkup with an increased white blood cell count which in follow-up studies and molecular detection of BCR-ABL (p210) fusions gene had been diagnosed as a Ph(+) typical CML. The upcoming question in this case scenario is whether developed CML is a secondary leukemia due to previous ALL chemotherapy or just a relapse case of primary leukemia.
