Early diagnosis of retinoblastoma: usefulness of searching for RB1 gene mutations

BACKGROUND: Retinoblastoma, the intraocular malignancy most common in child ren, occurs in both familial and sporadic (bilateral or unilateral). Heredi tary predisposition is caused by a germ-line mutation while non-hereditary is due to two somatic mutations in a retinal cell. This work was carried ou t in order to analyse genetically, the high number of families with some af fected member and to go deep into the molecular mechanisms responsible of t his pathology. PATIENTS AND METHOD: 59 families with one or more affected members were ana lysed. Cytogenetics and with polymorphic markers studies were carried out a nd a search for mutations was performed in DNA from white cells and from av ailable tumoral tissue. RESULTS: In four of the 5 familial cases, the responsible mutation was esta blished, the same as in 9 of the 13 bilateral sporadic. In the 7% of the un ilateral sporadic cases, mutation was found in leucocytary DNA, Lost of het erozygosity as a second mutational event was mainly due to mitotic recombin ation. CONCLUSIONS: Among the mutations of our series, a higher frequency of punct ual mutations, responsible of the first mutational event, was observed at c onstitutional level. Lost of heterozygosity was the mechanism observed in t he majority of the tumours.