title: Genomic Alterations of Non-Coding Regions Underlie Human Cancer: Lessons from T-ALL.
abstract: It has been appreciated for decades that somatic genomic alterations that change coding sequences of proto-oncogenes, translocate enhancers/promoters near proto-oncogenes, or create fusion oncogenes can drive cancer by inducing oncogenic activities. An explosion of genome-wide technologies over the past decade has fueled discoveries of the roles of three-dimensional chromosome structure and powerful cis-acting elements (super-enhancers) in regulating gene transcription. In recent years, studies of human T cell acute lymphoblastic leukemia (T-ALL) using genome-wide technologies have provided paradigms for how non-coding genomic region alterations can disrupt 3D chromosome architecture or establish super-enhancers to activate oncogenic transcription of proto-oncogenes. These studies raise important issues to consider with the objective of leveraging basic knowledge into new diagnostic and therapeutic opportunities for cancer patients.
authors.affiliation: Division of Cancer Pathobiology, Department of Pathology and Laboratory Medicine, Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Cell and Molecular Biology Graduate Group, Department of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Adrian
authors.initials: A
authors.lastname: Rivera-Reyes
authors.affiliation: Division of Cancer Pathobiology, Department of Pathology and Laboratory Medicine, Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Katharina E
authors.initials: KE
authors.lastname: Hayer
authors.affiliation: Division of Cancer Pathobiology, Department of Pathology and Laboratory Medicine, Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Cell and Molecular Biology Graduate Group, Department of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: bassing@email.chop.edu.
authors.forename: Craig H
authors.initials: CH
authors.lastname: Bassing
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D000066630:Ectopic Gene Expression; D015973:Gene Expression Regulation, Leukemic; D015894:Genome, Human; D006801:Humans; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D015533:Transcriptional Activation
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; C067143:TAL1 protein, human