Key rates for the grades and transformation ability of glioma: model simulations and clinical cases

Tumor progression to higher grade is a fundamental property of cancer. The malignant advancement of the pathological features may either develop during the later stages of cancer growth (natural evolution) or it may necessitate new mutations or molecular events that alter the rates of growth, disper...

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Published in:	Journal of neuro-oncology Vol. 133; no. 2; pp. 377 - 388
Main Authors:	Scribner, Elizabeth, Hackney, James R., Machemehl, Hannah C., Afiouni, Reina, Patel, Krishna R., Fathallah-Shaykh, Hassan M.
Format:	Journal Article
Language:	English
Published:	New York Springer US 01-06-2017 Springer Nature B.V
Subjects:	Adult Angiogenesis Brain cancer Brain Neoplasms - diagnostic imaging Brain Neoplasms - genetics Brain Neoplasms - physiopathology Brain tumors Cell Transformation, Neoplastic Clinical Study Disease Progression Female Genetic transformation Glial Fibrillary Acidic Protein Glioma Glioma - diagnostic imaging Glioma - genetics Glioma - physiopathology Humans Isocitrate Dehydrogenase - genetics Magnetic Resonance Imaging Male Medicine Medicine & Public Health Middle Aged Models, Biological Models, Theoretical Mutation Neurology Oncology Retrospective Studies Severity of Illness Index Vascularization X-linked Nuclear Protein - genetics Angiogenesis Rates Transformation Motility Glioma Mitosis Glioblastoma
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Summary:	Tumor progression to higher grade is a fundamental property of cancer. The malignant advancement of the pathological features may either develop during the later stages of cancer growth (natural evolution) or it may necessitate new mutations or molecular events that alter the rates of growth, dispersion, or neovascularization (transformation). Here, we model the pathological and radiological features of grades 2–4 gliomas at the times of diagnosis and death and study grade development and the progression to higher grades. We perform a retrospective review of clinical cases based on model predictions. Simulations uncover two unusual patterns of glioma progression, which are supported by clinical cases: (1) some grades 2 and 3 gliomas lack the ability of progression to higher grades, and (2) grade 3 glioma may evolve to GBM in a few weeks. All 13 gliomas that recurred at the same grade carry either the IDH1-R132H or the ATRX mutation. All (five of five) grade 3 tumors are 1p/19q co-deleted, IDH1-R132H mutated and ATRX wt. Furthermore, three of seven grade 2 gliomas are both IDH1-R132H mutated and ATRX mutated. Simulations replicate the good prognosis of secondary GBM. The results support the hypothesis that constant rates of dispersion, proliferation, and angiogenesis prescribe either a natural evolution or the inability to progress to higher grades. Furthermore, the accrual of molecular events that change a tumor’s ability to infiltrate, proliferate or neovascularize may transform the glioma either into a more aggressive tumor at the same grade or elevate its grade.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0167-594X 1573-7373
DOI:	10.1007/s11060-017-2444-6