The Genetic Basis of Hepatosplenic T-cell Lymphoma.
Fiche publication
Date publication
avril 2017
Journal
Cancer discovery
Auteurs
Membres identifiés du Cancéropôle Est :
Dr NICOLAE Alina
Tous les auteurs :
McKinney M, Moffitt AB, Gaulard P, Travert M, De Leval L, Nicolae A, Raffeld M, Jaffe ES, Pittaluga S, Xi L, Heavican T, Iqbal J, Belhadj K, Delfau-Larue MH, Fataccioli V, Czader MB, Lossos IS, Chapman-Fredricks JR, Richards KL, Fedoriw Y, Ondrejka SL, Hsi ED, Low L, Weisenburger D, Chan WC, Mehta-Shah N, Horwitz S, Bernal-Mizrachi L, Flowers CR, Beaven AW, Parihar M, Baseggio L, Parrens M, Moreau A, Sujobert P, Pilichowska M, Evens AM, Chadburn A, Au-Yeung RK, Srivastava G, Choi WW, Goodlad JR, Aurer I, Basic-Kinda S, Gascoyne RD, Davis NS, Li G, Zhang J, Rajagopalan D, Reddy A, Love C, Levy S, Zhuang Y, Datta J, Dunson DB, Davé SS
Lien Pubmed
Résumé
Hepatosplenic T-cell lymphoma (HSTL) is a rare and lethal lymphoma; the genetic drivers of this disease are unknown. Through whole-exome sequencing of 68 HSTLs, we define recurrently mutated driver genes and copy-number alterations in the disease. Chromatin-modifying genes, including , and , were commonly mutated in HSTL, affecting 62% of cases. HSTLs manifest frequent mutations in (31%), (9%), and (9%), for which there currently exist potential targeted therapies. In addition, we noted less frequent events in , and was the most frequently silenced gene in HSTL. We experimentally demonstrated that acts as a tumor suppressor gene. In addition, we found that mutations in and activate critical signaling pathways important to cell survival in HSTL. Our work thus defines the genetic landscape of HSTL and implicates gene mutations linked to HSTL pathogenesis and potential treatment targets. We report the first systematic application of whole-exome sequencing to define the genetic basis of HSTL, a rare but lethal disease. Our work defines as a tumor suppressor gene in HSTL and implicates genes including and in the disease. .
Mots clés
ATPases Associated with Diverse Cellular Activities, Adolescent, Adult, Aged, Base Sequence, Child, Child, Preschool, DNA Helicases, genetics, DNA-Binding Proteins, Enhancer of Zeste Homolog 2 Protein, Exome, genetics, Female, Histone-Lysine N-Methyltransferase, genetics, Humans, Liver Neoplasms, complications, Lymphoma, T-Cell, complications, Male, Middle Aged, Proto-Oncogene Proteins p21(ras), Splenic Neoplasms, complications, Transcription Factors, Tumor Suppressor Protein p53, genetics, Tumor Suppressor Proteins, genetics, Young Adult
Référence
Cancer Discov. 2017 04;7(4):369-379