MUTATIONS IN RB1 GENE IN RETINOBLASTOMA PATIENTS

PARMA, DIANA; LUCE, LEONELA; CARCIONE, MICAELA; MAZZANTI, CHIARA; GILIBERTO, FLORENCIA; SZIJAN, IRENE

Congreso; LXV Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2020

Retinoblastoma (RB) is the most frequent intraocular malignant tumorin childhood, caused by mutations in RB1 tumor suppressorgene. RB may be hereditary (bilateral tumors) or non-hereditary(mostly unilateral tumors). The first mutation can be germinal (RBhereditary) or somatic (RB non-hereditary), the second mutation isalways somatic. RB is a potentially curable cancer depending onearly diagnosis and treatment. Besides, patients with hereditaryRB can transmit the predisposition to their offspring. The aim of ourwork is the identification of RB1 mutations, for risk assessment inthe offspring and siblings of bilateral patients and for discriminationbetween hereditary and non-hereditary RB in unilateral patients.Out of a total of 215 patients with RB studied in our lab, the resultsof 2 bilateral and 2 unilateral are presented here. Mutationaldetection was conducted by a combined approach of Exome analysisand MLPA. Variants in donor splicing sites were detected inthe 2 bilateral patients: c.1389+1G>A and c.2106+1del. Moreover,a newly born sibling could be excluded from RB risk. One of theunilateral patients showed a homozygous deletion of RB1 entiregene and surrounding genes (ITM2B-5,RCBTB2-8,DLEU1-2) inthe tumor; this mutation was not present in blood DNA, denoting anon-hereditary RB. The other unilateral patient displayed a heterozygousgermline deletion of whole RB1 gene and neighboring genes(ITM2B-5,RCBTB2-8,DLEU1-2,PCDH8-3,PCDH8-2), denoting ahereditary RB and a likely contiguous deletion syndrome. The 3? endwas not found, that is, the deletion continues beyond PCDH8.Identification of RB1 mutations allows detection of RB predispositionin patient´s offspring and siblings which provides access to earlytreatment to preserve survival and vision. Identification of germinalmutations in unilateral patients allows detecting the risk of tumordevelopment in the other eye and its absence eliminates the needfor frequent eye exams under anesthesia.