Niyaz Zaman1, Serena Santhana Dass1, Persephone DU Parcq2, Suzanne Macmahon3, Lewis Gallagher3, Lisa Thompson3, Jamshid S Khorashad4, Clara LimbÄck-Stanic5,2. 1. Division of Brain Sciences, Department of Medicine, Imperial College London, London, U.K. 2. Department of Cell Pathology, Imperial College Healthcare NHS Trust, London, U.K. 3. Clinical Genomics, The Centre for Molecular Pathology, The Royal Marsden NHS Foundation Trust, London, U.K. 4. Department of Immunology and Inflammation, Imperial College London, London, U.K. 5. Division of Brain Sciences, Department of Medicine, Imperial College London, London, U.K. climback@ic.ac.uk.
Abstract
BACKGROUND/AIM: Better diagnostic and prognostic markers are required for a more accurate diagnosis and an earlier detection of glioma progression and for suggesting better treatment strategies. This retrospective study aimed to identify actionable gene variants to define potential markers of clinical significance. MATERIALS AND METHODS: 56 glioblastomas (GBM) and 44 grade 2-3 astrocytomas were profiled with next generation sequencing (NGS) as part of routine diagnostic workup and bioinformatics analysis was used for the identification of variants. CD34 immunohistochemistry (IHC) was used to measure microvessel density (MVD) and Log-rank test to compare survival and progression in the presence or absence of these variants. RESULTS: Bioinformatic analysis highlighted frequently occurring variants in genes involved in angiogenesis regulation (KDR, KIT, TP53 and PIK3CA), with the most common ones being KDR (rs1870377) and KIT (rs3822214). The KDR variant was associated with increased MVD and shorter survival in GBM. We did not observe any correlation between the KIT variant and MVD; however, there was an association with tumour grade. CONCLUSION: This study highlights the role of single-nucleotide variants (SNVs) that may be considered non-pathogenic and suggests the prognostic significance for survival of KIT rs3822214 and KDR rs1870377 and potential importance in planning new treatment strategies for gliomas. Copyright
BACKGROUND/AIM: Better diagnostic and prognostic markers are required for a more accurate diagnosis and an earlier detection of glioma progression and for suggesting better treatment strategies. This retrospective study aimed to identify actionable gene variants to define potential markers of clinical significance. MATERIALS AND METHODS: 56 glioblastomas (GBM) and 44 grade 2-3 astrocytomas were profiled with next generation sequencing (NGS) as part of routine diagnostic workup and bioinformatics analysis was used for the identification of variants. CD34 immunohistochemistry (IHC) was used to measure microvessel density (MVD) and Log-rank test to compare survival and progression in the presence or absence of these variants. RESULTS: Bioinformatic analysis highlighted frequently occurring variants in genes involved in angiogenesis regulation (KDR, KIT, TP53 and PIK3CA), with the most common ones being KDR (rs1870377) and KIT (rs3822214). The KDR variant was associated with increased MVD and shorter survival in GBM. We did not observe any correlation between the KIT variant and MVD; however, there was an association with tumour grade. CONCLUSION: This study highlights the role of single-nucleotide variants (SNVs) that may be considered non-pathogenic and suggests the prognostic significance for survival of KIT rs3822214 and KDR rs1870377 and potential importance in planning new treatment strategies for gliomas. Copyright
Authors: P B Vermeulen; G Gasparini; S B Fox; M Toi; L Martin; P McCulloch; F Pezzella; G Viale; N Weidner; A L Harris; L Y Dirix Journal: Eur J Cancer Date: 1996-12 Impact factor: 9.162
Authors: David N Louis; Arie Perry; Guido Reifenberger; Andreas von Deimling; Dominique Figarella-Branger; Webster K Cavenee; Hiroko Ohgaki; Otmar D Wiestler; Paul Kleihues; David W Ellison Journal: Acta Neuropathol Date: 2016-05-09 Impact factor: 17.088
Authors: Jann N Sarkaria; Gaspar J Kitange; C David James; Ruth Plummer; Hilary Calvert; Michael Weller; Wolfgang Wick Journal: Clin Cancer Res Date: 2008-05-15 Impact factor: 12.531
Authors: Debyani Chakravarty; Jianjiong Gao; Sarah M Phillips; Ritika Kundra; Hongxin Zhang; Jiaojiao Wang; Julia E Rudolph; Rona Yaeger; Tara Soumerai; Moriah H Nissan; Matthew T Chang; Sarat Chandarlapaty; Tiffany A Traina; Paul K Paik; Alan L Ho; Feras M Hantash; Andrew Grupe; Shrujal S Baxi; Margaret K Callahan; Alexandra Snyder; Ping Chi; Daniel Danila; Mrinal Gounder; James J Harding; Matthew D Hellmann; Gopa Iyer; Yelena Janjigian; Thomas Kaley; Douglas A Levine; Maeve Lowery; Antonio Omuro; Michael A Postow; Dana Rathkopf; Alexander N Shoushtari; Neerav Shukla; Martin Voss; Ederlinda Paraiso; Ahmet Zehir; Michael F Berger; Barry S Taylor; Leonard B Saltz; Gregory J Riely; Marc Ladanyi; David M Hyman; José Baselga; Paul Sabbatini; David B Solit; Nikolaus Schultz Journal: JCO Precis Oncol Date: 2017-05-16
Authors: Sara E Patterson; Rangjiao Liu; Cara M Statz; Daniel Durkin; Anuradha Lakshminarayana; Susan M Mockus Journal: Hum Genomics Date: 2016-01-16 Impact factor: 4.639