title: Gene mutations and actionable genetic lesions in mantle cell lymphoma.
abstract: Mutations and epigenetic alterations are key events in transforming normal cells to cancer cells. Mantle cell lymphoma (MCL), a non-Hodgkin's lymphoma of the B-cell, is an aggressive malignancy with poor prognosis especially for those patients who are resistant to the frontline drugs. There is a great need to describe the molecular basis and mechanism of drug resistance in MCL to develop new strategies for treatment. We reviewed frequent somatic mutations and mutations involving the B-cell pathways in MCL and discussed clinical trials that attempted to disrupt these gene pathways and/or epigenetic events. Recurrent gene mutations were discussed in the light of prognostic and therapeutic opportunity and also the challenges of targeting these lesions. Mutations in the ATM, CCND1, TP53, MLL2, TRAF2 and NOTCH1 were most frequently encountered in mantle cell lymphoma. Translational models should be built that would assess mutations longitudinally to identify important compensatory, pro-survival and anti-apoptic pathways and actionable genetic targets.
authors.affiliation: Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|The University of Texas Health Science Centre, Houston, Texas, USA.
authors.forename: Makhdum
authors.initials: M
authors.lastname: Ahmed
authors.affiliation: Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Leo
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Krystle
authors.initials: K
authors.lastname: Nomie
authors.affiliation: Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Lam
authors.affiliation: Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Wang
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism; D002461:Cell Line, Transformed; D002869:Chromosome Aberrations; D019938:Cyclin D1 / Q000235:genetics; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics; D044127:Epigenesis, Genetic; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D057285:Precision Medicine; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D051881:Receptor, Notch1 / Q000235:genetics; D012008:Recurrence; D012074:Remission Induction; D015398:Signal Transduction; D047992:TNF Receptor-Associated Factor 2 / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: C000595707:BCL2 protein, human; C530104:CCND1 protein, human; D004268:DNA-Binding Proteins; C120898:KMT2D protein, human; C497761:NOTCH1 protein, human; D009363:Neoplasm Proteins; C101338:PSMD2 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051881:Receptor, Notch1; D047992:TNF Receptor-Associated Factor 2; C495901:TP53 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1
keywords: MCL (mantle cell lymphoma); actionable genetic lesions; epigenetic; gene targets; mutations