Geno-16to Catalog the Molecular Alterations Identified During Genomic Analysis of Gliomas and the Utility in Personalizing Therapy
Year: 2015
Type: article
Study design: Observational Study
Abstract: OBJECTIVE: To catalog the molecular alterations identified during genomic analysis of gliomas, and the utility in personalizing therapy. BACKGROUND: Recent advances in genomic analysis technologies using microarrays and next generation sequencing (NGS) have advanced our understanding of gliomas with a main goal to individualize therapy tailored to molecular and genomic profile of the tumor. One method is FoundationOne, a commercialized NGS-based assay panel designed to include all genes known to be somatically altered in solid tumors with periodic updates. DESIGN/METHODS: A retrospective study involved reviewing charts and Foundation Medicine results after IRB approval. RESULTS: We identified 45 patients with gliomas, WHO grades II-IV, from whom 45 tumors were analyzed. The FoundationOne results showed genomically significant alterations with available targeted therapy in 31/45 (68.8%). The most commonly identified alterations were in EGFR (33.3%, 15/45), including amplification (13), EGFRvIII mutation (7), other EGFR mutations (6) patients. Other frequently identified mutations involved PTEN (40%, 18/45), IDH1/2 (17.7%, 8/45), and FGFR3 (6.6%, 3/45). Therapy options and/or treatment changed based on the result in 15/45 (31.1%) of patients. Targeted therapy was tailored to EGFR in 12/15 (80%), FGFR3 mutation in 1/15 (6.6%), KDR amplification in 1/15 (6.6%) and NF1 in 1/15 (6.6%) of patients. Those therapies were either prescribed off-label (60%, 9/15) or as part of a clinical trial (40%, 6/15). Targeted therapy not offered most frequently due to enrollment in clinical trial not targeted to genetic alteration (8.8%, 4/45), good response on standard therapy (2%, 1/45), disease progression and death (2%, 1/45), international patients (2%, 1/45), and patient preference to seek alternative medicine internationally (2%, 1/45). CONCLUSIONS: Gliomas remain relatively resistant to approved therapies and using advanced technology in genetic analysis to individualize therapy is promising. The impact of targeting treatment based on individual key molecular alterations must be validated in prospective studies.
Source: Neuro-Oncology
Language: English
Subfield: Genetics (clinical)
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2336636428