Cell of origin of glioma: biological and clinical implications

Llaguno, Sheila Alcantara; Parada, Luis F.

doi:10.1038/bjc.2016.354

Cited by 127 publications

(78 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…10). Neurospheres currently represent the best model of neural stem cells (NSCs) 36 and our findings are in line with the current hypothesis that undifferentiated NSCs and more committed progenitor cells give rise to all abovementioned gliomas [37][38][39][40] . Of note, our findings also recapitulate the historical understanding of the distinct COOs for gliomas and CNS-Medullo wherein gliomas were thought to derive from glia cells, while CNS-Medullo was believed to derive from neuronal-type cells 41,42 .…”

Section: Chromatin Differences Between Cell Differentiation States Insupporting

confidence: 90%

Tumor mutational landscape is a record of the pre-malignant state

Kübler

Haradhvala

et al. 2019

Preprint

View full text Add to dashboard Cite

Chromatin structure has a major influence on the cell-specific density of somatic mutations along the cancer genome. Here, we present a pan-cancer study in which we searched for the putative cancer cell-of-origin of 2,550 whole genomes, representing 32 cancer types by matching their mutational landscape to the regional patterns of chromatin modifications ascertained in 104 normal tissue types. We found that, in almost all cancer types, the cell-of-origin can be predicted solely from their DNA sequences. Our analysis validated the hypothesis that high-grade serous ovarian cancer originates in the fallopian tube and identified distinct origins of breast cancer subtypes. We also demonstrated that the technique is equally capable of identifying the cell-of-origin for a series of 2,044 metastatic samples from 22 of the tumor types available as primaries. Moreover, cancer drivers, whether inherited or acquired, reside in active chromatin regions in the respective cell-of-origin. Taken together, our findings highlight that many somatic mutations accumulate while the chromatin structure of the cell-of-origin is maintained and that this historical record, captured in the DNA, can be used to identify the often elusive cancer cell-of-origin.

show abstract

Section: Chromatin Differences Between Cell Differentiation States Insupporting

confidence: 90%

Tumor mutational landscape is a record of the pre-malignant state

Kübler

Haradhvala

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…The neuronal regulation of normal oligodendrocyte precursor cell proliferation that is important to the process of myelin plasticity suggests that similar mechanisms could play a role in the aberrant proliferation of brain cancers that molecularly resemble OPCs. High‐grade gliomas such as glioblastoma (GBM) and diffuse intrinsic pontine glioma (DIPG), the most lethal forms of brain cancer in adults and in children, respectively, are thought to originate from OPCs or earlier stem cells (Alcantara Llaguno et al, ; Liu et al, ; Monje and Dietrich, ; Galvao et al, ; Alcantara Llaguno et al, ; Tate et al, ; Alcantara Llaguno and Parada, ; Nagaraja et al, ). Oligodendroglioma, another important glioma type chiefly affecting adults, is similarly thought to arise from oligodendroglial lineage precursors (Persson et al, ; Sugiarto et al, ).…”

Section: Myelin Plasticity In Diseasementioning

confidence: 99%

Bad wrap: Myelin and myelin plasticity in health and disease

Gibson

Geraghty

Monje

2017

Developmental Neurobiology

View full text Add to dashboard Cite

Human central nervous system myelin development extends well into the fourth decade of life, and this protracted period underscores the potential for experience to modulate myelination. The concept of myelin plasticity implies adaptability in myelin structure and function in response to experiences during development and beyond. Mounting evidence supports this concept of neuronal activity-regulated changes in myelin-forming cells, including oligodendrocyte precursor cell proliferation, oligodendrogenesis and modulation of myelin microstructure. In healthy individuals, myelin plasticity in associative white matter structures of the brain is implicated in learning and motor function in both rodents and humans. Activity-dependent changes in myelin-forming cells may influence the function of neural networks that depend on the convergence of numerous neural signals on both a temporal and spatial scale. However, dysregulation of myelin plasticity can disadvantageously alter myelin microstructure and result in aberrant circuit function or contribute to pathological cell proliferation. Emerging roles for myelin plasticity in normal neurological function and in disease are discussed. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 123-135, 2018.

show abstract

“…Note that there is currently no genetically engineered mouse model based on overexpression and activation of the PDGFRα receptor, a genomic event that is highly relevant to GBM. By using these models, several research groups, including ours, have uncovered important aspects of GBM biology, including the identity of GBM cells of origin [Alcantara Llaguno and Parada, ] and the role of cancer stem cell in the initiation and maintenance of GBM [Jun et al, ]. In addition, few GEMMs of glioma have also been utilized to study sensitivity and resistance to various treatment modalities (recently reviewed in [McNeill et al, ]).…”

Section: Gemms Of Gbmsmentioning

confidence: 99%

Immune Checkpoint Blockade Biology in Mouse Models of Glioblastoma

Yeo

Charest

2017

J. Cell. Biochem.

View full text Add to dashboard Cite

Glioblastoma Multiforme (GBM) is a highly malignant primary brain cancer that is associated with abysmal prognosis. The median survival of GBM patients is ~15 months and there have not been any significant advance in therapies in over a decade, leaving treatment options limited. There is clearly an unmet need for GBM treatment. Immunotherapies are treatments based on usurping the power of the host's immune system to recognize and eliminate cancer cells. They have recently proven to be a successful strategy for combating a variety of cancers. Of the various types of immunotherapies, checkpoint blockade approaches have thus far produced significant clinical responses in several cancers including melanoma, non small-cell lung cancer, renal cancer and prostate cancer. This review focuses on the biological rationale for using checkpoint blockade immunotherapeutic approaches in primary brain cancer and an up-to-date summary of current and ongoing checkpoint inhibitors-based clinical trials for malignant glioma. In addition, we expand on new concepts for further improving checkpoint blockade treatments, with a particular focus on the advantages of using genetically engineered mouse models for studies of immunotherapies in GBM.

show abstract

Cell of origin of glioma: biological and clinical implications

Cited by 127 publications

References 31 publications

Tumor mutational landscape is a record of the pre-malignant state

Tumor mutational landscape is a record of the pre-malignant state

Bad wrap: Myelin and myelin plasticity in health and disease

Immune Checkpoint Blockade Biology in Mouse Models of Glioblastoma

Contact Info

Product

Resources

About