Molecular diagnosis in patients with retinoblastoma: Report of a series of cases

ObjectivesTo report the benefits of genetic diagnosis in patients with retinoblastoma.MethodObservational study. Patients with retinoblastoma and their families were included. Demographic and clinical data were recorded. Blood and tumor samples were obtained. Next generation sequencing was performed on the samples. When deletion 13 q syndrome was suspected, cytogenetics microarray was performed (Cytoscan® HD, Affymetrix, Santa Clara, CA, USA), with a high density chip of 1.9 million of non-polymorphic probes and 750 thousand SNP probes.ResultsOf the 7 cases were analyzed 4 were male. The mean age at diagnosis was 21 months (range 5–36). Three cases had bilateral retinoblastoma, and 4 unilateral. None had family history. In all patients, blood was analyzed, and a study was performed on the tissue from 2 unilateral enucleated tumors, in which 6 mutations were identified, all de novo. Just one was novel (c.164delC; case 1). One case of unilateral tumor revealed blood mosaicism, showing that his condition was inheritable, and that there is a high risk of developing retinoblastoma in the unaffected eye. The patient also has an increased risk of presenting with other primary tumors.ConclusionMolecular diagnosis of RB1 in patients with retinoblastoma impacts on the decision process, costs, treatment, and prognosis of patients, as well as their families.

ResumenObjetivosReportar los beneficios del diagnóstico genético en una serie de pacientes con retinoblastoma.MétodosEstudio longitudinal observacional. Se incluyó a pacientes con retinoblastoma y sus familias. Se registraron datos demográficos y clínicos. Se obtuvieron muestras de sangre y del tumor, realizándose análisis mediante next generation sequencing. Con la sospecha de síndrome de deleción 13q, se realizó análisis citogenético con cariotipo molecular (Cytoscan® HD, Affymetrix, Santa Clara, CA, EE. UU.), utilizando un chip de alta densidad con 1,9 millones de sondas únicas no polimórficas y 750.000 sondas de SNP.ResultadosSe analizan 7 casos. Cuatro eran hombres. La mediana de edad del diagnóstico fue de 21 meses (rango 5–36). Tres casos presentaron retinoblastoma bilateral y 4, unilateral. Ninguno tenía antecedentes familiares. En todos se estudió la sangre y en los 2 pacientes unilaterales enucleados se estudió el tejido tumoral. Se encontraron 6 mutaciones, todas fueron de novo. Solo una era nueva (c.164delC; caso 1). Un caso de tumor unilateral reveló un mosaicismo en sangre, por lo que su enfermedad es heredable, tiene riesgo de desarrollar retinoblastoma en el ojo contralateral sano y riesgo de presentar otros tumores primarios.ConclusiónEl diagnóstico molecular de RB1 en pacientes con retinoblastoma influye sobre la toma de decisiones, los costos, el tratamiento y el pronóstico de los pacientes y sus familias.