Mutations in the RB1 gene in Argentine retinoblastoma patients and their clinical correlation

OTTAVIANI DANIELA ; PARMA DIANA; FERRER MARCELA; GILIBERTO FLORENCIA; LUCE LEONELA; ALONSO CRISTINA; CHANTADA GUILLERMO; SZIJAN IRENE

OPHTHALMIC GENETICS

TAYLOR & FRANCIS INC

Lugar: Londres; Año: 2015

1381-6810

Background: Retinoblastoma, the most common childhood ocular cancer, is caused by inactivation of the RB1 tumor suppressor gene in the developing retina. It may occur as unilateral, bilateral or rarely as multicentric retinoblastoma, including pineal or suprasellar tumors. A second non-ocular tumor may develop in adult bilateral patients. Retinoblastoma may rarely associate with Down syndrome. Being the retinoblastoma a hereditary cancer identification of the causative mutations is important for risk prediction in patient´s relatives. An early detection of the tumor is critical for survival and eye preservation. Methods: A total of 20 patients with unilateral, bilateral and multicentric retinoblastoma were studied by segregation of polymorphisms, DNA sequencing and MLPA analyses. Results: Six germline and seven somatic mutations were identified; they include nonsense, frameshift, splice mutations and gross rearrangements, some of them uncommon such as duplications (intraexonic, interexonic and of whole RB1 gene). Three out of four nonsense/frameshift germline mutations were associated with severe phenotype: bilateral and multicentric retinoblastomas. The at-risk-haplotype was identified in a familial case including one patient with osteosarcoma, it was useful for detection of mutation carriers. Conclusions: screening for germline and somatic mutations in retinoblastoma patients revealed the causative mutations, being several of them rare. Different clinical presentations of retinoblastoma, some uncommon, enabled us to investigate the correlation between genotype and phenotype, which is vital for genetic counseling.