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Rapid Test Accurately Profiles Brain Tumor Genetics

By LabMedica International staff writers
Posted on 09 Feb 2016
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Image: Histopathology of a brain tumor called oligodendroglioma diagnosed by the highly cellular lesion composed of cells resembling fried eggs with distinct cell borders moderate-to-marked nuclear atypia (Photo courtesy of Nephron).
Image: Histopathology of a brain tumor called oligodendroglioma diagnosed by the highly cellular lesion composed of cells resembling fried eggs with distinct cell borders moderate-to-marked nuclear atypia (Photo courtesy of Nephron).
Brain tumors can be rapidly and accurately profiled with a next-generation, gene-sequencing test recently developed. The test, called GlioSeq, is now being used by oncologists to help guide treatment planning of brain cancers.

Historically, the diagnosis of central nervous system (CNS) tumors has been based primarily on histopathologic features. However, patients with morphologically identical tumors may experience different clinical outcomes and responses to treatment because the underlying genetic characteristics of the tumors differ.

Scientists at the University of Pittsburgh Schools of the Health Sciences (PA, USA) and their colleagues used GlioSeq, a next-generation, gene-sequencing assay, to test 54 adult and pediatric brain tumor samples for genetic abnormalities, including point mutations, gene fusions, and small gene insertions and deletions that had already been characterized by other means. They used next-generation sequencing to simultaneously identify all previously known alterations, as well as many additional genetic markers in these tumors. This provided important information on classification of these tumors, and on possible new targets for therapy.

The teams identified 30 genes with genetic alterations repeatedly found in CNS tumors and designed custom DNA primer pools to generate libraries and sequence more than 1,360 CNS tumor-related hot spots of more than13,000 all cancer hot spots). The GlioSeq performance was evaluated in 54 CNS tumor specimens collected in 2012–2015, including 28 formalin-fixed, paraffin-embedded (FFPE) and 26 snap-frozen tissues. DNA library preparation and sequencing were successful in 54 of 54 (100%) specimens tested. The investigators compared the GlioSeq cost of reagents with the cost of reagents using conventional techniques such as Sanger sequencing, reverse transcription polymerase chain reaction (RT-PCR), and single nucleotide polymorphism array, that are needed to detect all types of genetic alterations and determined that conventional methods would cost 15 times more than GlioSeq analysis.

Frank S. Lieberman, MD, a professor of neurology, neurosurgery and medical oncology and co-author of the study said, “This test can help guide the physician and the patient in planning treatment, since the molecular information allows us to more precisely characterize tumors and more confidently predict survival and response to therapy. In addition, Glioseq facilitates the identification of clinical trial options with the appropriate molecular targets, as well as cases in which molecularly targeted drugs are available.” The study was published on December 17, 2015, in the journal Neuro-Oncology.

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University of Pittsburgh Schools of the Health Sciences


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