The goal of the proposed study is to evaluate the role of noninvasive imaging parameters as biomarkers of malignant transformation in diffuse low grade glioma and to use these parameters to select regions for characterizing the genetic mutations associated with recurrent disease. The studies will have a significant impact on the management of these patients by providing objective criteria to predict when a lesion transforms to a more malignant phenotype, whether and where to intervene surgically and how to select the next line therapy. This is an important problem because patients with tumors that recur from a prior LGG have different outcomes depending on histological subtype, grade, and molecular/cytogenetic features. The mechanisms of malignant transformation are unclear and treatment strategies are often pursued without histological confirmation of recurrent tumor. In our previous SPORE Project, we applied magnetic resonance imaging (MRi) and spectroscopic imaging (MRS!) to evaluate 125 patients prior to resection of tumors that were thought to have recurred from a prior LGG. Significant differences in the in vivo MR measures were seen for tumors with malignant transformation compared to those that did not. Ex vivo analysis of the histological status, IDHI mutations and ex-vivo NMR spectra from the image guided tissue samples provided new information that resulted in novel hypotheses being investigated in Specific Aim 1. Extending this approach by defining the mutation profile using next-generation sequencing of image guided tissue samples with defined histology will increase the probability of identifying mutations that drive malignant transformation and address, for the first time, the tumor genome evolution associated with treatment effects and the natural history of the disease.
Specific Aim 1 will relate in-vivo MR parameters to malignant transfomriation and clinical outcome and Specific Aim 2 will use paired samples from lesions that either do or do not have the characteristics of malignant transformation, as well as paired samples from the current and subsequent surgery to examine the evolution of the mutation profile. The knowledge gained will make a major impact upon patient care.
; This novel project will integrate non-invasive imaging markers that predict malignant transformation with an evaluation of the spatial and temporal patterns of changes in genetic mutations of patients who present with recurrent disease from an original diagnosis of low grade glioma. This will inform on the mechanisms of malignant transformation and will facilitate the development of strategies to prevent or treat the recurrence.
|Amirian, E Susan; Scheurer, Michael E; Zhou, Renke et al. (2016) History of chickenpox in glioma risk: a report from the glioma international case-control study (GICC). Cancer Med 5:1352-8|
|Amirian, E Susan; Armstrong, Georgina N; Zhou, Renke et al. (2016) The Glioma International Case-Control Study: A Report From the Genetic Epidemiology of Glioma International Consortium. Am J Epidemiol 183:85-91|
|Koestler, Devin C; Jones, Meaghan J; Usset, Joseph et al. (2016) Improving cell mixture deconvolution by identifying optimal DNA methylation libraries (IDOL). BMC Bioinformatics 17:120|
|Walsh, Kyle M; Ohgaki, Hiroko; Wrensch, Margaret R (2016) Epidemiology. Handb Clin Neurol 134:3-18|
|Phillips, Joanna J; Gong, Henry; Chen, Katharine et al. (2016) Activating NRF1-BRAF and ATG7-RAF1 fusions in anaplastic pleomorphic xanthoastrocytoma without BRAF p.V600E mutation. Acta Neuropathol 132:757-760|
|Ladomersky, Erik; Zhai, Lijie; Gritsina, Galina et al. (2016) Advanced age negatively impacts survival in an experimental brain tumor model. Neurosci Lett 630:203-8|
|Dasgupta, Tina; Olow, Aleksandra K; Yang, Xiaodong et al. (2016) Survival advantage combining a BRAF inhibitor and radiation in BRAF V600E-mutant glioma. J Neurooncol 126:385-93|
|Duleh, Steve; Wang, Xianhong; Komirenko, Allison et al. (2016) Activation of the Keap1/Nrf2 stress response pathway in autophagic vacuolar myopathies. Acta Neuropathol Commun 4:115|
|Amirian, E Susan; Zhou, Renke; Wrensch, Margaret R et al. (2016) Approaching a Scientific Consensus on the Association between Allergies and Glioma Risk: A Report from the Glioma International Case-Control Study. Cancer Epidemiol Biomarkers Prev 25:282-90|
|Ojha, Juhi; Codd, Veryan; Nelson, Christopher P et al. (2016) Genetic Variation Associated with Longer Telomere Length Increases Risk of Chronic Lymphocytic Leukemia. Cancer Epidemiol Biomarkers Prev 25:1043-9|
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