@article{3085766,
    title = "EGR2 mutations define a new clinically aggressive subgroup of chronic lymphocytic leukemia",
    author = "Young, E. and Noerenberg, D. and Mansouri, L. and Ljungström, V. and Frick, M. and Sutton, L.-A. and Blakemore, S.J. and Galan-Sousa, J. and Plevova, K. and Baliakas, P. and Rossi, D. and Clifford, R. and Roos-Weil, D. and Navrkalova, V. and Dörken, B. and Schmitt, C.A. and Smedby, K.E. and Juliusson, G. and Giacopelli, B. and Blachly, J.S. and Belessi, C. and Panagiotidis, P. and Chiorazzi, N. and Davi, F. and Langerak, A.W. and Oscier, D. and Schuh, A. and Gaidano, G. and Ghia, P. and Xu, W. and Fan, L. and Bernard, O.A. and Nguyen-Khac, F. and Rassenti, L. and Li, J. and Kipps, T.J. and Stamatopoulos, K. and Pospisilova, S. and Zenz, T. and Oakes, C.C. and Strefford, J.C. and Rosenquist, R. and Damm, F.",
    journal = "Leukemia Research",
    year = "2017",
    volume = "31",
    number = "7",
    pages = "1547-1554",
    publisher = "Nature Publishing Group",
    issn = "0145-2126",
    doi = "10.1038/leu.2016.359",
    keywords = "ATM protein;  biological marker;  CD38 antigen;  early growth response factor 2;  Notch1 receptor;  protein p53;  early growth response factor 2;  EGR2 protein, human, adult;  advanced cancer;  aged;  antigen expression;  Article;  cancer patient;  cancer prognosis;  cancer screening;  cancer survival;  chronic lymphatic leukemia;  female;  gene frequency;  gene mutation;  groups by age;  human;  major clinical study;  male;  mutational analysis;  overall survival;  priority journal;  prognostic assessment;  sequence analysis;  time to treatment;  classification;  genetics;  Leukemia, Lymphocytic, Chronic, B-Cell;  middle aged;  mortality;  mutation;  proportional hazards model;  tumor suppressor gene, Adult;  Aged;  Early Growth Response Protein 2;  Female;  Genes, p53;  Humans;  Leukemia, Lymphocytic, Chronic, B-Cell;  Male;  Middle Aged;  Mutation;  Proportional Hazards Models",
    abstract = "Recurrent mutations within EGR2 were recently reported in advanced-stage chronic lymphocytic leukemia (CLL) patients and associated with a worse outcome. To study their prognostic impact, 2403 CLL patients were examined for mutations in the EGR2 hotspot region including a screening (n=1283) and two validation cohorts (UK CLL4 trial patients, n=366; CLL Research Consortium (CRC) patients, n=490). Targeted deep-sequencing of 27 known/postulated CLL driver genes was also performed in 38 EGR2-mutated patients to assess concurrent mutations. EGR2 mutations were detected in 91/2403 (3.8%) investigated cases, and associated with younger age at diagnosis, advanced clinical stage, high CD38 expression and unmutated IGHV genes. EGR2-mutated patients frequently carried ATM lesions (42%), TP53 aberrations (18%) and NOTCH1/FBXW7 mutations (16%). EGR2 mutations independently predicted shorter time-to-first-treatment (TTFT) and overall survival (OS) in the screening cohort; they were confirmed associated with reduced TTFT and OS in the CRC cohort and independently predicted short OS from randomization in the UK CLL4 cohort. A particularly dismal outcome was observed among EGR2-mutated patients who also carried TP53 aberrations. In summary, EGR2 mutations were independently associated with an unfavorable prognosis, comparable to CLL patients carrying TP53 aberrations, suggesting that EGR2-mutated patients represent a new patient subgroup with very poor outcome. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved."
}