cancers Review Tumor Heterogeneity in Glioblastomas: From Light Microscopy to Molecular Pathology Aline P. Becker 1,* , Blake E. Sells 2 , S. Jaharul Haque 1 and Arnab Chakravarti 1 1 Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USA;
[email protected] (S.J.H.);
[email protected] (A.C.) 2 Medical Scientist Training Program, Washington University in St. Louis, St. Louis, MO 63310, USA;
[email protected] * Correspondence:
[email protected] Simple Summary: Glioblastomas (GBMs) are the most frequent and aggressive malignant tumors arising in the human brain. One of the main reasons for GBM aggressiveness is its diverse cellular composition, comprised by differentiated tumor cells, tumor stem cells, cells from the blood vessels, and inflammatory cells, which simultaneously affect multiple cellular functions involved in cancer development. “Tumor Heterogeneity” usually encompasses both inter-tumor heterogeneity, differ- ences observed at population level; and intra-tumor heterogeneity, differences among cells within individual tumors, which directly affect outcomes and response to treatment. In this review, we briefly describe the evolution of GBM classification yielded from inter-tumor heterogeneity studies and discuss how the technological development allows for the characterization of intra-tumor hetero- geneity, beginning with differences based on histopathological features of GBM until the molecular alterations in DNA, RNA, and proteins observed at individual cells. Citation: Becker, A.P.; Sells, B.E.; Abstract: One of the main reasons for the aggressive behavior of glioblastoma (GBM) is its intrinsic Haque, S.J.; Chakravarti, A. Tumor intra-tumor heterogeneity, characterized by the presence of clonal and subclonal differentiated tumor Heterogeneity in Glioblastomas: cell populations, glioma stem cells, and components of the tumor microenvironment, which affect From Light Microscopy to Molecular multiple hallmark cellular functions in cancer.