Banavathy S Kruthika1, Ruchi Jain2, A Arivazhagan3, R D Bharath4, T C Yasha1, Paturu Kondaiah2, Vani Santosh5. 1. Department of Neuropathology, National Institute of Mental Health and Neuroscience, Bangalore, India. 2. Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, India. 3. Department of Neurosurgery, National Institute of Mental Health and Neuroscience, Bangalore, India. arivazhagan.a@gmail.com. 4. Department of Neuroimaging and Interventional Radiology, National Institute of Mental Health and Neuroscience, Bangalore, India. 5. Department of Neuropathology, National Institute of Mental Health and Neuroscience, Bangalore, India. vani.santosh@gmail.com.
Abstract
PURPOSE: Peritumoural brain zone (PT) of glioblastoma (GBM) is the area where tumour recurrence is often observed. We aimed to identify differentially regulated genes between tumour core (TC) and PT to understand the underlying molecular characteristics of infiltrating tumour cells in PT. METHODS: 17 each histologically characterised TC and PT tissues of GBM along with eight control tissues were subjected to cDNA Microarray. PT tissues contained 25-30% infiltrating tumour cells. Data was analysed using R Bioconductor software. Shortlisted genes were validated using qRT-PCR. Expression of one selected candidate gene, PDZ Binding Kinase (PBK) was correlated with patient survival, tumour recurrence and functionally characterized in vitro using gene knock-down approach. RESULTS: Unsupervised hierarchical clustering showed that TC and PT have distinct gene expression profiles compared to controls. Further, comparing TC with PT, we observed a significant overlap in gene expression profile in both, despite PT having fewer infiltrating tumour cells. qRT-PCR for 13 selected genes validated the microarray data. Expression of PBK was higher in PT as compared to TC and recurrent when compared to newly diagnosed GBM tumours. PBK knock-down showed a significant reduction in cell proliferation, migration and invasion with increase in sensitivity to radiation and Temozolomide treatment. CONCLUSIONS: We show that several genes of TC are expressed even in PT contributing to the vulnerability of PT for tumour recurrence. PBK is identified as a novel gene up-regulated in PT of GBM with a strong role in conferring aggressiveness, including radio-chemoresistance, thus contributing to recurrence in GBM tumours.
PURPOSE: Peritumoural brain zone (PT) of glioblastoma (GBM) is the area where tumour recurrence is often observed. We aimed to identify differentially regulated genes between tumour core (TC) and PT to understand the underlying molecular characteristics of infiltrating tumour cells in PT. METHODS: 17 each histologically characterised TC and PT tissues of GBM along with eight control tissues were subjected to cDNA Microarray. PT tissues contained 25-30% infiltrating tumour cells. Data was analysed using R Bioconductor software. Shortlisted genes were validated using qRT-PCR. Expression of one selected candidate gene, PDZ Binding Kinase (PBK) was correlated with patient survival, tumour recurrence and functionally characterized in vitro using gene knock-down approach. RESULTS: Unsupervised hierarchical clustering showed that TC and PT have distinct gene expression profiles compared to controls. Further, comparing TC with PT, we observed a significant overlap in gene expression profile in both, despite PT having fewer infiltrating tumour cells. qRT-PCR for 13 selected genes validated the microarray data. Expression of PBK was higher in PT as compared to TC and recurrent when compared to newly diagnosed GBM tumours. PBK knock-down showed a significant reduction in cell proliferation, migration and invasion with increase in sensitivity to radiation and Temozolomide treatment. CONCLUSIONS: We show that several genes of TC are expressed even in PT contributing to the vulnerability of PT for tumour recurrence. PBK is identified as a novel gene up-regulated in PT of GBM with a strong role in conferring aggressiveness, including radio-chemoresistance, thus contributing to recurrence in GBM tumours.
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: Patricia Ruiz-Ontañon; Jose L Orgaz; Beatriz Aldaz; Alberto Elosegui-Artola; Juan Martino; Maria T Berciano; Juan A Montero; Lara Grande; Lorena Nogueira; Santiago Diaz-Moralli; Azucena Esparís-Ogando; Alfonso Vazquez-Barquero; Miguel Lafarga; Atanasio Pandiella; Marta Cascante; Victor Segura; Jose A Martinez-Climent; Victoria Sanz-Moreno; Jose L Fernandez-Luna Journal: Stem Cells Date: 2013-06 Impact factor: 6.277