Genomic profiling of medulloblastomas

Medulloblastoma is the most common malignant brain tumor in children. Multimodality treatment regimens involving surgery, chemotherapy and radiotherapy, have significantly improved survival rates for this disease; however, approximately one third of patients with medulloblastoma remain incurable...

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Main Author: Teo, Wan-Yee
Other Authors: Ching Lau
Format: Thesis
Language:English
Published: 2014
Subjects:
Online Access:http://hdl.handle.net/10356/61806
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author Teo, Wan-Yee
author2 Ching Lau
author_facet Ching Lau
Teo, Wan-Yee
author_sort Teo, Wan-Yee
collection NTU
description Medulloblastoma is the most common malignant brain tumor in children. Multimodality treatment regimens involving surgery, chemotherapy and radiotherapy, have significantly improved survival rates for this disease; however, approximately one third of patients with medulloblastoma remain incurable and current treatment result in severe neurocognitive sequelae among long term survivors. Outcome prediction using clinical parameters and biomarkers has failed, owing to the biological heterogeneity of medulloblastomas. Molecular profiling offers an attractive approach for risk stratification of treatment and has identified at least two distinct subgroups of medulloblastoma with activation of sonic hedgehog and Wingless pathways; the remaining subgroups are poorly defined. Granule cell precursors are believed to be the cell of origin of at least a subset of medulloblastoma. Aim 1: We hypothesized that the gene expression of medulloblastoma is possibly accounted for by not only the pathogenesis of the tumor, but also the cell of origin. We hypothesized that the medulloblastoma subgroups which are non-sonic-hedgehog-activated arise from a different cell of origin and speculate that knowledge on the identity of the cell of origin may provide insights to the tumorigenesis of the poorly understood subgroups of tumors. We also explored independent prognostic biological markers within each molecularly distinct medulloblastoma subgroup for higher clinical utility. Aim 2: To elucidate the role of the immune system in the biology and clinical outcome of medulloblastoma, we hypothesize that immune cells infiltrating medulloblastoma create a unique microenvironment which may alter the tumor biology an immune-regulated gene expression signature that can be linked to prognostic outcome.
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spelling ntu-10356/618062023-02-28T18:46:50Z Genomic profiling of medulloblastomas Teo, Wan-Yee Ching Lau School of Biological Sciences DRNTU::Science::Biological sciences Medulloblastoma is the most common malignant brain tumor in children. Multimodality treatment regimens involving surgery, chemotherapy and radiotherapy, have significantly improved survival rates for this disease; however, approximately one third of patients with medulloblastoma remain incurable and current treatment result in severe neurocognitive sequelae among long term survivors. Outcome prediction using clinical parameters and biomarkers has failed, owing to the biological heterogeneity of medulloblastomas. Molecular profiling offers an attractive approach for risk stratification of treatment and has identified at least two distinct subgroups of medulloblastoma with activation of sonic hedgehog and Wingless pathways; the remaining subgroups are poorly defined. Granule cell precursors are believed to be the cell of origin of at least a subset of medulloblastoma. Aim 1: We hypothesized that the gene expression of medulloblastoma is possibly accounted for by not only the pathogenesis of the tumor, but also the cell of origin. We hypothesized that the medulloblastoma subgroups which are non-sonic-hedgehog-activated arise from a different cell of origin and speculate that knowledge on the identity of the cell of origin may provide insights to the tumorigenesis of the poorly understood subgroups of tumors. We also explored independent prognostic biological markers within each molecularly distinct medulloblastoma subgroup for higher clinical utility. Aim 2: To elucidate the role of the immune system in the biology and clinical outcome of medulloblastoma, we hypothesize that immune cells infiltrating medulloblastoma create a unique microenvironment which may alter the tumor biology an immune-regulated gene expression signature that can be linked to prognostic outcome. ​Doctor of Philosophy (SBS) 2014-10-27T01:08:59Z 2014-10-27T01:08:59Z 2012 2012 Thesis Teo, W.-Y. (2012). Genomic profiling of medulloblastomas. Doctoral thesis, Nanyang Technological University, Singapore. http://hdl.handle.net/10356/61806 en 194 p. application/pdf
spellingShingle DRNTU::Science::Biological sciences
Teo, Wan-Yee
Genomic profiling of medulloblastomas
title Genomic profiling of medulloblastomas
title_full Genomic profiling of medulloblastomas
title_fullStr Genomic profiling of medulloblastomas
title_full_unstemmed Genomic profiling of medulloblastomas
title_short Genomic profiling of medulloblastomas
title_sort genomic profiling of medulloblastomas
topic DRNTU::Science::Biological sciences
url http://hdl.handle.net/10356/61806
work_keys_str_mv AT teowanyee genomicprofilingofmedulloblastomas