Tumor Heterogeneity in Glioblastomas: From Light Microscopy to Molecular Pathology

One of the main reasons for the aggressive behavior of glioblastoma (GBM) is its intrinsic intra-tumor heterogeneity, characterized by the presence of clonal and subclonal differentiated tumor cell populations, glioma stem cells, and components of the tumor microenvironment, which affect multiple ha...

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Main Authors: Aline P. Becker, Blake E. Sells, S. Jaharul Haque, Arnab Chakravarti
Format: Article
Language:English
Published: MDPI AG 2021-02-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/13/4/761
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author Aline P. Becker
Blake E. Sells
S. Jaharul Haque
Arnab Chakravarti
author_facet Aline P. Becker
Blake E. Sells
S. Jaharul Haque
Arnab Chakravarti
author_sort Aline P. Becker
collection DOAJ
description One of the main reasons for the aggressive behavior of glioblastoma (GBM) is its intrinsic intra-tumor heterogeneity, characterized by the presence of clonal and subclonal differentiated tumor cell populations, glioma stem cells, and components of the tumor microenvironment, which affect multiple hallmark cellular functions in cancer. “Tumor Heterogeneity” usually encompasses both <i>inter-tumor heterogeneity</i> (population-level differences); and <i>intra-tumor heterogeneity</i> (differences within individual tumors). Tumor heterogeneity may be assessed in a single time point (spatial heterogeneity) or along the clinical evolution of GBM (longitudinal heterogeneity). Molecular methods may detect clonal and subclonal alterations to describe tumor evolution, even when samples from multiple areas are collected in the same time point (spatial-temporal heterogeneity). In GBM, although the inter-tumor mutational landscape is relatively homogeneous, intra-tumor heterogeneity is a striking feature of this tumor. In this review, we will address briefly the inter-tumor heterogeneity of the CNS tumors that yielded the current glioma classification. Next, we will take a deeper dive in the intra-tumor heterogeneity of GBMs, which directly affects prognosis and response to treatment. Our approach aims to follow technological developments, allowing for characterization of intra-tumor heterogeneity, beginning with differences on histomorphology of GBM and ending with molecular alterations observed at single-cell level.
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spelling doaj.art-004c604d27fb48c89a46f4d98d4adc722023-12-11T16:49:55ZengMDPI AGCancers2072-66942021-02-0113476110.3390/cancers13040761Tumor Heterogeneity in Glioblastomas: From Light Microscopy to Molecular PathologyAline P. Becker0Blake E. Sells1S. Jaharul Haque2Arnab Chakravarti3Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USAMedical Scientist Training Program, Washington University in St. Louis, St. Louis, MO 63310, USAComprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USAComprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USAOne of the main reasons for the aggressive behavior of glioblastoma (GBM) is its intrinsic intra-tumor heterogeneity, characterized by the presence of clonal and subclonal differentiated tumor cell populations, glioma stem cells, and components of the tumor microenvironment, which affect multiple hallmark cellular functions in cancer. “Tumor Heterogeneity” usually encompasses both <i>inter-tumor heterogeneity</i> (population-level differences); and <i>intra-tumor heterogeneity</i> (differences within individual tumors). Tumor heterogeneity may be assessed in a single time point (spatial heterogeneity) or along the clinical evolution of GBM (longitudinal heterogeneity). Molecular methods may detect clonal and subclonal alterations to describe tumor evolution, even when samples from multiple areas are collected in the same time point (spatial-temporal heterogeneity). In GBM, although the inter-tumor mutational landscape is relatively homogeneous, intra-tumor heterogeneity is a striking feature of this tumor. In this review, we will address briefly the inter-tumor heterogeneity of the CNS tumors that yielded the current glioma classification. Next, we will take a deeper dive in the intra-tumor heterogeneity of GBMs, which directly affects prognosis and response to treatment. Our approach aims to follow technological developments, allowing for characterization of intra-tumor heterogeneity, beginning with differences on histomorphology of GBM and ending with molecular alterations observed at single-cell level.https://www.mdpi.com/2072-6694/13/4/761glioblastomatumor microenvironmentprecision medicinegliomaneoplastic stem cellsprognosis
spellingShingle Aline P. Becker
Blake E. Sells
S. Jaharul Haque
Arnab Chakravarti
Tumor Heterogeneity in Glioblastomas: From Light Microscopy to Molecular Pathology
Cancers
glioblastoma
tumor microenvironment
precision medicine
glioma
neoplastic stem cells
prognosis
title Tumor Heterogeneity in Glioblastomas: From Light Microscopy to Molecular Pathology
title_full Tumor Heterogeneity in Glioblastomas: From Light Microscopy to Molecular Pathology
title_fullStr Tumor Heterogeneity in Glioblastomas: From Light Microscopy to Molecular Pathology
title_full_unstemmed Tumor Heterogeneity in Glioblastomas: From Light Microscopy to Molecular Pathology
title_short Tumor Heterogeneity in Glioblastomas: From Light Microscopy to Molecular Pathology
title_sort tumor heterogeneity in glioblastomas from light microscopy to molecular pathology
topic glioblastoma
tumor microenvironment
precision medicine
glioma
neoplastic stem cells
prognosis
url https://www.mdpi.com/2072-6694/13/4/761
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AT blakeesells tumorheterogeneityinglioblastomasfromlightmicroscopytomolecularpathology
AT sjaharulhaque tumorheterogeneityinglioblastomasfromlightmicroscopytomolecularpathology
AT arnabchakravarti tumorheterogeneityinglioblastomasfromlightmicroscopytomolecularpathology