HGG-04. A HIGH-THROUGHPUT IN VITRO DRUG SCREEN OF PATIENT-DERIVED GLIOMATOSIS CEREBRI CELLS FOR PRECISION MEDICINE

• Published in: Neuro-oncology (Charlottesville, Va.) Vol. 19; no. suppl_4; p. iv23
• Main Authors: Maachani, Uday Bhanu, Rajappa, Prajwal, Voronina, Julia C., Souweidane, Mark M., Greenfield, Jeffrey P.
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.06.2017
• Subjects: Abstracts
• ISSN: 1522-8517; 1523-5866
• DOI: 10.1093/neuonc/nox083.093

Gliomatosis cerebri (GC) represents a rare inoperable astrocytic neoplasm, characterized by extensive diffuse infiltration into three or more lobes of the brain, sometimes forming one or more discreet tumor masses. It is found in children, teenagers, and adults. The origin of the tumor is unknown and an absence of representative cell cultures for GC has made it difficult to study GC biology. Many current therapeutic approaches have failed and novel targeted therapies are urgently needed. In the present study, we describe the establishment of patient-derived GC cells from the biopsy of a temporal lobe portion of a GC tumor in a 9yr old male. Following the biopsy and creation of a GC-derived cell line, identification of drugs of potential interest was performed utilizing high-throughput drug screen and next generation whole exome sequencing (NGS) of the patient’s tumor. We delineated candidate therapeutics unique for this case, including BRAF, VEGFR/PDGFR inhibitors, FGFR inhibitors, and CDK inhibitors. Sensitivity to these inhibitors mirrored the genetic and somatic mutation/alterations within this tumor. Somatic PIK3CA point mutations were detected at adaptor-binding domain (ABD-G106V) of the p110α catalytic subunit, along with PDGFRA (N659K) mutation. Copy number alterations (CNA) included partial focal CDKN2A and CDKN2B deletion. Further, various other genomic alterations in cancer genes of known and unknown significance were also identified. Our findings demonstrate the feasibility of using patient-derived gliomatosis cerebri cell cultures for high-throughput assays and their integration in drug testing, tailoring treatment strategies based on individual tumor genetic profiles.