title: Genomic signatures in T-cell lymphoma: How can these improve precision in diagnosis and inform prognosis?
abstract: The novel genetic information gained from genome-wide high throughput techniques has greatly improved our understanding of peripheral T-cell lymphoma (PTCL). PTCL consists of numerous distinct entities and is currently diagnosed using a combination of clinical and morphologic features and immunophenotyping together with limited molecular assays leading to an often fragmented, complicated diagnostic system. The diagnosis of many cases is challenging even for expert hematopathologists and more than a third of the cases cannot be further classified and thus put into the PTCL-NOS category. Gene expression profiling (GEP) has significantly improved the molecular classification of PTCLs and identified robust molecular signatures for common nodal subtypes of PTCL including angioimmunoblastic T-cell lymphoma (AITL), anaplastic T-cell lymphoma (ALCL), adult T-cell leukemia/lymphoma (ATLL) and extra-nodal NK/T cell lymphoma (ENKTL). These studies also led to identification of novel molecular subtypes with distinct prognosis, that otherwise could not be identified by conventional methods. Integration of massive sequencing strategies and gene expression has characterized driver genetic alterations in common subtypes like AITL, ALCL, ENKTL and other PTCLs. These studies have identified oncogenic pathways and genes affected in specific disease subtypes that can be potentially targeted by specific therapies. Novel treatment options with FDA approved drugs directed towards mutant IDH2, the NF-κB, JAK/STAT, or mTOR pathways illustrate the usefulness of genome-wide techniques to identify targets for therapy. In this review, we highlight recent advances in the molecular diagnosis and prognosis of PTCL using these genome-wide techniques.
authors: Department of Pathology and Microbiology, Center for Lymphoma and Leukemia Research, University of Nebraska Medical Center, Omaha, NE, USA. Electronic address: jiqbal@unmc.edu.
authors: Javeed
authors: J
authors: Iqbal
authors: Department of Internal Medicine, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
authors: Ryan
authors: R
authors: Wilcox
authors: Department of Pathology and Microbiology, Center for Lymphoma and Leukemia Research, University of Nebraska Medical Center, Omaha, NE, USA.
authors: Hina
authors: H
authors: Naushad
authors: Department of Pathology and Microbiology, Center for Lymphoma and Leukemia Research, University of Nebraska Medical Center, Omaha, NE, USA; Department of Pathology, City of Hope Medical Center, CA, USA.
authors: Joseph
authors: J
authors: Rohr
authors: Department of Pathology and Microbiology, Center for Lymphoma and Leukemia Research, University of Nebraska Medical Center, Omaha, NE, USA.
authors: Tayla B
authors: TB
authors: Heavican
authors: Department of Pathology and Microbiology, Center for Lymphoma and Leukemia Research, University of Nebraska Medical Center, Omaha, NE, USA; Department of Pathology, City of Hope Medical Center, CA, USA.
authors: Chao
authors: C
authors: Wang
authors: Department of Pathology and Microbiology, Center for Lymphoma and Leukemia Research, University of Nebraska Medical Center, Omaha, NE, USA.
authors: Alyssa
authors: A
authors: Bouska
authors: Department of Pathology and Microbiology, Center for Lymphoma and Leukemia Research, University of Nebraska Medical Center, Omaha, NE, USA.
authors: Kai
authors: K
authors: Fu
authors: Department of Pathology, City of Hope Medical Center, CA, USA. Electronic address: jochan@coh.org.
authors: Wing C
authors: WC
authors: Chan
authors: Department of Hematology/Oncology, University of Nebraska Medical Center, Omaha, NE, USA.
authors: Julie M
authors: JM
authors: Vose
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D019468:Disease Management; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055106:Genome-Wide Association Study; D023281:Genomics / Q000379:methods; D006801:Humans; D016399:Lymphoma, T-Cell / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D058990:Molecular Targeted Therapy; D009154:Mutation; D011379:Prognosis; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents
keywords: Molecular classification; gene expression profiling; molecular prognosis; peripheral T-cell lymphoma; targeted therapy