CRX MRNA AS A BIOMARKER FOR RETINOBLASTOMA CELL IN METASTATIC SITES AND IN PATIENTDERIVED XENOGRAFT

ASCHERO ROSARIO; SCHAIQUEVICH PAULA; CHANTADA GUILLERMO; ZUGBI SANTIAGO; LUBIENIECKI FABIANA; WINTER URSULA; ANA VANESA TORBIDONI

Congreso; LXI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC); 2016

Introduction: The cone-rod homeobox (CRX) transcriptionfactor is expressed in retinoblastoma tumors and in normal retina, but not inother tissues. We used it asspecific biomarker for detectionof retinoblastoma cells in samples from patients with metastaticretinoblastoma. Objectives: To confirm the presence of retinoblastoma cells insamples from metastatic patients and in patient-derived xenografts (PDXs) using CRX detection. Material and Methods: Extraocular samples were taken from metastatic retinoblastomapatients (n=3) and those with tumor cellsinvasion were inoculatedin the flank of nude mice (patient-derived xenograft: PDX). After tumors grew, they were removed and processed. RNA from the samples was extracted and mRNA of CRX was detected by retrotranscription followby Real Time PCR. Results: Patient1: Samples from orbital tumor (OT) andcervical lymph node (CLN) were both positives for CRX, confirming the presenceof retinoblastoma cells. CRX expression in peripheral blood (PB), bone marrow(BM) and cerebrospinal fluid (CSF) was negative, dismissing the presence ofretinoblastoma cells. PDXs were obtained from OT and CLN and after growing, we confirmed its retinoblastoma naturethrough CRX detection that was positive for both PDXs. Patient2: Samples from PB, BM and CSF were evaluated for presence of retinoblastomacell. CSF was positive forCRX, confirming the presence ofretinoblastoma cells. This sample was inoculated in a nude mouse, and after growingits retinoblastomanaturewas confirmed through CRX presence. Patient3: Retinoblastoma cells weredetected in OT and in BM through CRX positivity. Both tissues were inoculated in nude mice, but only OT grew. The retinoblastoma nature of the PDX wasconfirmed through CRX presence. Conclusions: We successfully obtain PDXs fromextraocular retinoblastoma patients. CRX is expressed in retinoblastoma cellsalso in PDXs, being auseful tool for confirming the retinoblastoma cells in PDXs and metastaticsites.