RB1 gene mutations in Argentine retinoblastoma patients. Correlation with clinical features.

PARMA DIANA; FERRER MARCELA; LUCE LEONELA; FLORENCIA GILIBERTO,; I SZIJAN

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2017

1932-6203

Retinoblastoma is an inherited childhood ocular cancer caused by mutations in the tumor suppressor RB1 gene. Identification of mutations is essential for risk assessment in relatives. Retinoblastoma is a potentially curable cancer and an early diagnosis is critical for survival and eye preservation. Unilateral retinoblastoma is mostly nonheritable (somatic mutations) while bilateral retinoblastoma is heritable (one germline and one somatic mutations), both have high penetrance, 90%. The purpose of this work was to identify the causative mutations in patients with different clinical presentations. A comprehensive approach was used to study a cohort of 25 patients with unilateral, bilateral and trilateral retinoblastoma. Blood and tumor DNA was analyzed by sequence and MLPA assays, validation of an insertion was performed by cloning the PCR product. Most patients had unilateral retinoblastoma, six had bilateraland one trilateral tumor with ocular and supraselar/selar locations. Other tumors in addition to retinoblastoma were found in the affected families. One patient had two syndromes, retinoblastoma and schwannomatosis, another RB patient had a father carrying a retinoma. Four out of 18 unilateral patients carried germinal mutations (22%), mostly missense. The bilateral/trilateral patients carried splice site, nonsense, frameshift mutations and a whole gene deletion. All these mutations were associated with severe phenotype: bilateral or trilateral. Missense mutations were associated with mild phenotype: unilateral retinoblastoma, retinoma or no tumor. This study allowed theidentification of causative RB1 mutations in bilateral and some unilateral patients, including 5 novel mutations. These data are crucial for genetic counseling and support the relevance of carrying out complete genetic screening for RB1 mutations in both constitutional and tumor tissues.