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129 results on '"Strefford, J C"'

1. EGR2 mutations define a new clinically aggressive subgroup of chronic lymphocytic leukemia

Author

Young, E, Noerenberg, D, Mansouri, L, Ljungström, V, Frick, M, Sutton, L-A, Blakemore, S J, Galan-Sousa, J, Plevova, K, Baliakas, P, Rossi, D, Clifford, R, Roos-Weil, D, Navrkalova, V, Dörken, B, Schmitt, C A, Smedby, K E, Juliusson, G, Giacopelli, B, Blachly, J S, Belessi, C, Panagiotidis, P, Chiorazzi, N, Davi, F, Langerak, A W, Oscier, D, Schuh, A, Gaidano, G, Ghia, P, Xu, W, Fan, L, Bernard, O A, Nguyen-Khac, F, Rassenti, L, Li, J, Kipps, T J, Stamatopoulos, K, Pospisilova, S, Zenz, T, Oakes, C C, Strefford, J C, Rosenquist, R, and Damm, F

Published
2017
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4. P624: CHROMOTHRIPSIS IN PATIENTS WITH CLL AND COMPLEX KARYOTYPE: PATTERNS OF ABERRATIONS AND PROGNOSTIC VALUE

Author

Ramos-Campoy, S., primary, Puiggros, A., additional, Kamaso, J., additional, Beà, S., additional, Bougeon, S., additional, Larráyoz, M. J., additional, Costa, D., additional, Parker, H., additional, Rigolin, G. M., additional, Blanco, M. L., additional, Collado, R., additional, Ancín, I., additional, Salgado, R., additional, Moro, M., additional, Baumann, T., additional, Gimeno, E., additional, Moreno, C., additional, Calasanz, M. J., additional, Cuneo, A., additional, Strefford, J. C., additional, Nguyen-Khac, F., additional, Oscier, D., additional, Haferlach, C., additional, Schoumans, J., additional, and Espinet, B., additional

Published
2022
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6. Recurrent mutations refine prognosis in chronic lymphocytic leukemia

Author

Baliakas, P, Hadzidimitriou, A, Sutton, L-A, Rossi, D, Minga, E, Villamor, N, Larrayoz, M, Kminkova, J, Agathangelidis, A, Davis, Z, Tausch, E, Stalika, E, Kantorova, B, Mansouri, L, Scarfò, L, Cortese, D, Navrkalova, V, Rose-Zerilli, M J J, Smedby, K E, Juliusson, G, Anagnostopoulos, A, Makris, A M, Navarro, A, Delgado, J, Oscier, D, Belessi, C, Stilgenbauer, S, Ghia, P, Pospisilova, S, Gaidano, G, Campo, E, Strefford, J C, Stamatopoulos, K, and Rosenquist, R

Published
2015
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7. Whole-exome sequencing in splenic marginal zone lymphoma reveals mutations in genes involved in marginal zone differentiation

Author

Martínez, N, Almaraz, C, Vaqué, J P, Varela, I, Derdak, S, Beltran, S, Mollejo, M, Campos-Martin, Y, Agueda, L, Rinaldi, A, Kwee, I, Gut, M, Blanc, J, Oscier, D, Strefford, J C, Martinez-Lopez, J, Salar, A, Sole, F, Rodriguez-Peralto, J L, Diez-Tascón, C, García, J F, Fraga, M, Sebastián, E, Alvés, J, Menárguez, J, González-Carreró, J, Casado, L F, Bayes, M, Bertoni, F, Gut, I, and Piris, M A

Published
2014
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9. Distinct patterns of novel gene mutations in poor-prognostic stereotyped subsets of chronic lymphocytic leukemia: the case of SF3B1 and subset #2

Author

Strefford, J C, Sutton, L-A, Baliakas, P, Agathangelidis, A, Malčíková, J, Plevova, K, Scarfó, L, Davis, Z, Stalika, E, Cortese, D, Cahill, N, Pedersen, L B, di Celle, P F, Tzenou, T, Geisler, C, Panagiotidis, P, Langerak, A W, Chiorazzi, N, Pospisilova, S, Oscier, D, Davi, F, Belessi, C, Mansouri, L, Ghia, P, Stamatopoulos, K, and Rosenquist, R

Published
2013
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20. Lamin B1 regulates somatic mutations and progression of B-cell malignancies

Author

Klymenko, T, Bloehdorn, J, Bahlo, J, Robrecht, S, Akylzhanova, G, Cox, K, Estenfelder, S, Wang, J, Edelmann, J, Strefford, J C, Wojdacz, T K, Fischer, K, Hallek, M, Stilgenbauer, S, Cragg, M, Gribben, J, and Braun, A

Subjects
CHROMATIN, B-Lymphocytes, Chromatin Immunoprecipitation, NUCLEAR LAMINA, Lamin Type B, CHRONIC LYMPHOCYTIC-LEUKEMIA, HYPERMUTATION, Immunoglobulin Variable Region, CLL8 TRIAL, Leukemia, Lymphocytic, Chronic, B-Cell, MEMORY B, PLASMA-CELLS, Cell Line, Tumor, Disease Progression, AID, Humans, Original Article, Somatic Hypermutation, Immunoglobulin, Immunoglobulin Heavy Chains, Lymphoma, Follicular, IMMUNOGLOBULIN GENES, GENE-EXPRESSION
Abstract

Somatic hypermutation (SHM) is a pivotal process in adaptive immunity that occurs in the germinal centre and allows B cells to change their primary DNA sequence and diversify their antigen receptors. Here, we report that genome binding of Lamin B1, a component of the nuclear envelope involved in epigenetic chromatin regulation, is reduced during B-cell activation and formation of lymphoid germinal centres. Chromatin immunoprecipitation-Seq analysis showed that kappa and heavy variable immunoglobulin domains were released from the Lamin B1 suppressive environment when SHM was induced in B cells. RNA interference-mediated reduction of Lamin B1 resulted in spontaneous SHM as well as kappa-light chain aberrant surface expression. Finally, Lamin B1 expression level correlated with progression-free and overall survival in chronic lymphocytic leukaemia, and was strongly involved in the transformation of follicular lymphoma. In summary, here we report that Lamin B1 is a negative epigenetic regulator of SHM in normal B-cells and a 'mutational gatekeeper', suppressing the aberrant mutations that drive lymphoid malignancy.

Published
2018

21. Lamin B1 regulates somatic mutations and progression of B-cell malignancies

Author

Klymenko, T., Bloehdorn, J., Bahlo, J., Robrecht, S., Akylzhanova, G., Cox, K., Estenfelder, S., Wang, J., Edelmann, J., Strefford, J. C., Wojdacz, T. K., Fischer, K., Hallek, M., Stilgenbauer, S., Cragg, M., Gribben, J., Braun, A., Klymenko, T., Bloehdorn, J., Bahlo, J., Robrecht, S., Akylzhanova, G., Cox, K., Estenfelder, S., Wang, J., Edelmann, J., Strefford, J. C., Wojdacz, T. K., Fischer, K., Hallek, M., Stilgenbauer, S., Cragg, M., Gribben, J., and Braun, A.

Abstract

Somatic hypermutation (SHM) is a pivotal process in adaptive immunity that occurs in the germinal centre and allows B cells to change their primary DNA sequence and diversify their antigen receptors. Here, we report that genome binding of Lamin B1, a component of the nuclear envelope involved in epigenetic chromatin regulation, is reduced during B-cell activation and formation of lymphoid germinal centres. Chromatin immunoprecipitation-Seq analysis showed that kappa and heavy variable immunoglobulin domains were released from the Lamin B1 suppressive environment when SHM was induced in B cells. RNA interference-mediated reduction of Lamin B1 resulted in spontaneous SHM as well as kappa-light chain aberrant surface expression. Finally, Lamin B1 expression level correlated with progression-free and overall survival in chronic lymphocytic leukaemia, and was strongly involved in the transformation of follicular lymphoma. In summary, here we report that Lamin B1 is a negative epigenetic regulator of SHM in normal B-cells and a 'mutational gatekeeper', suppressing the aberrant mutations that drive lymphoid malignancy.

Published
2018

23. Genomic disruption of the histone methyltransferase SETD2 in chronic lymphocytic leukaemia

Author

Parker, H, Rose Zerilli, M. J. J, Larrayoz, M, Clifford, R, Edelmann, J, Blakemore, S, Gibson, J, Wang, J, Ljungstr�m, V, Wojdacz, T. K, Chaplin, T, Roghanian, A, Davis, Z, Parker, A, Tausch, E, Ntoufa, S, Ramos, S, Robbe, P, Alsolami, R, Steele, A. J, Packham, G, Rodr�ez Vicente, A. E, Brown, L, Mcnicholl, F, Forconi, Francesco, Pettitt, A, Hillmen, P, Dyer, M, Cragg, M. S, Chelala, C, Oakes, C. C, Rosenquist, R, Stamatopoulos, K, Stilgenbauer, S, Knight, S, Schuh, A, Oscier, D. G, Strefford, J. C., Leukaemia & Lymphoma Research (UK), Royal Marsden NHS Foundation Trust, The Institute of Cancer Research (UK), Swedish Research Council, Swedish Cancer Society, Polysackaridforskning i Uppsala AB, German Research Foundation, Leukaemia Foundation, Wessex Medical Research, Kay Kendall Leukaemia Fund, and Cancer Research UK

Subjects
Male, Ataxia Telangiectasia Mutated Proteins, Disease-Free Survival, Humans, Genes, Tumor Suppressor, Hematologi, Chronic, Cancer och onkologi, Leukemia, B-Cell, Genomics, Histone-Lysine N-Methyltransferase, Hematology, Prognosis, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphocytic, Survival Rate, Mutation, Tumor Suppressor Protein p53, Genes, Cancer and Oncology, Histone Methyltransferases, Female, Original Article, Tumor Suppressor
Abstract

Histone methyltransferases (HMTs) are important epigenetic regulators of gene transcription and are disrupted at the genomic level in a spectrum of human tumours including haematological malignancies. Using high-resolution single nucleotide polymorphism (SNP) arrays, we identified recurrent deletions of the SETD2 locus in 3% (8/261) of chronic lymphocytic leukaemia (CLL) patients. Further validation in two independent cohorts showed that SETD2 deletions were associated with loss of TP53, genomic complexity and chromothripsis. With next-generation sequencing we detected mutations of SETD2 in an additional 3.8% of patients (23/602). In most cases, SETD2 deletions or mutations were often observed as a clonal event and always as a mono-allelic lesion, leading to reduced mRNA expression in SETD2-disrupted cases. Patients with SETD2 abnormalities and wild-type TP53 and ATM from five clinical trials employing chemotherapy or chemo-immunotherapy had reduced progression-free and overall survival compared with cases wild type for all three genes. Consistent with its postulated role as a tumour suppressor, our data highlight SETD2 aberration as a recurrent, early loss-of-function event in CLL pathobiology linked to aggressive disease., This work was funded by Bloodwise (11052, 12036), the Kay Kendall Leukaemia Fund (873), Cancer Research UK (C34999/A18087, ECMC C24563/A15581), Wessex Medical Research and the Bournemouth Leukaemia Fund. SS is supported by the Else Kröner-FreseniusStiftung (2012_A146) and Deutsche Forschungsgemeinschaft (SFB 1074 projects B1, B2). The LRF CLL4 trial was funded by a core grant from Leukaemia and Lymphoma Research. DG and DC acknowledge the support by The Royal Marsden Hospital and The Institute of Cancer Research National Institute of Health Research Biomedical Research Center. RR is supported by the Swedish Cancer Society, the Swedish Research Council, Science for Life Laboratory, Uppsala University, Uppsala University Hospital, and the Lion’s Cancer Research Foundation, Uppsala.

Published
2016

24. Lamin B1 regulates somatic mutations and progression of B-cell malignancies

Author

Klymenko, T, primary, Bloehdorn, J, additional, Bahlo, J, additional, Robrecht, S, additional, Akylzhanova, G, additional, Cox, K, additional, Estenfelder, S, additional, Wang, J, additional, Edelmann, J, additional, Strefford, J C, additional, Wojdacz, T K, additional, Fischer, K, additional, Hallek, M, additional, Stilgenbauer, S, additional, Cragg, M, additional, Gribben, J, additional, and Braun, A, additional

Published
2017
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25. Genomic disruption of the histone methyltransferase SETD2 in chronic lymphocytic leukaemia

Author

Parker, H., Rose-Zerilli, M. J. J., Larrayoz, M., Clifford, R., Edelmann, J., Blakemore, S., Gibson, J., Wang, J., Ljungström, Viktor, Wojdacz, T. K., Chaplin, T., Roghanian, A., Davis, Z., Parker, A., Tausch, E., Ntoufa, S., Ramos, S., Robbe, P., Alsolami, R., Steele, A. J., Packham, G., Rodriguez-Vicente, A. E., Brown, L., McNicholl, F., Forconi, F., Pettitt, A., Hillmen, P., Dyer, M., Cragg, M. S., Chelala, C., Oakes, C. C., Rosenquist, Richard, Stamatopoulos, K., Stilgenbauer, S., Knight, S., Schuh, A., Oscier, D. G., Strefford, J. C., Parker, H., Rose-Zerilli, M. J. J., Larrayoz, M., Clifford, R., Edelmann, J., Blakemore, S., Gibson, J., Wang, J., Ljungström, Viktor, Wojdacz, T. K., Chaplin, T., Roghanian, A., Davis, Z., Parker, A., Tausch, E., Ntoufa, S., Ramos, S., Robbe, P., Alsolami, R., Steele, A. J., Packham, G., Rodriguez-Vicente, A. E., Brown, L., McNicholl, F., Forconi, F., Pettitt, A., Hillmen, P., Dyer, M., Cragg, M. S., Chelala, C., Oakes, C. C., Rosenquist, Richard, Stamatopoulos, K., Stilgenbauer, S., Knight, S., Schuh, A., Oscier, D. G., and Strefford, J. C.

Abstract

Histone methyltransferases (HMTs) are important epigenetic regulators of gene transcription and are disrupted at the genomic level in a spectrum of human tumours including haematological malignancies. Using high-resolution single nucleotide polymorphism (SNP) arrays, we identified recurrent deletions of the SETD2 locus in 3% (8/261) of chronic lymphocytic leukaemia (CLL) patients. Further validation in two independent cohorts showed that SETD2 deletions were associated with loss of TP53, genomic complexity and chromothripsis. With next-generation sequencing we detected mutations of SETD2 in an additional 3.8% of patients (23/602). In most cases, SETD2 deletions or mutations were often observed as a clonal event and always as a mono-allelic lesion, leading to reduced mRNA expression in SETD2-disrupted cases. Patients with SETD2 abnormalities and wild-type TP53 and ATM from five clinical trials employing chemotherapy or chemo-immunotherapy had reduced progression-free and overall survival compared with cases wild type for all three genes. Consistent with its postulated role as a tumour suppressor, our data highlight SETD2 aberration as a recurrent, early loss-of-function event in CLL pathobiology linked to aggressive disease., De tre första författarna delar förstaförfattarskapet.

Published
2016
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26. EGR2 mutations define a new clinically aggressive subgroup of chronic lymphocytic leukemia

Author

Young, E, primary, Noerenberg, D, additional, Mansouri, L, additional, Ljungström, V, additional, Frick, M, additional, Sutton, L-A, additional, Blakemore, S J, additional, Galan-Sousa, J, additional, Plevova, K, additional, Baliakas, P, additional, Rossi, D, additional, Clifford, R, additional, Roos-Weil, D, additional, Navrkalova, V, additional, Dörken, B, additional, Schmitt, C A, additional, Smedby, K E, additional, Juliusson, G, additional, Giacopelli, B, additional, Blachly, J S, additional, Belessi, C, additional, Panagiotidis, P, additional, Chiorazzi, N, additional, Davi, F, additional, Langerak, A W, additional, Oscier, D, additional, Schuh, A, additional, Gaidano, G, additional, Ghia, P, additional, Xu, W, additional, Fan, L, additional, Bernard, O A, additional, Nguyen-Khac, F, additional, Rassenti, L, additional, Li, J, additional, Kipps, T J, additional, Stamatopoulos, K, additional, Pospisilova, S, additional, Zenz, T, additional, Oakes, C C, additional, Strefford, J C, additional, Rosenquist, R, additional, and Damm, F, additional

Published
2016
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28. ATM mutations in major stereotyped subsets of chronic lymphocytic leukemia: enrichment in subset #2 is associated with markedly short telomeres

Author

Navrkalova, V., primary, Young, E., additional, Baliakas, P., additional, Radova, L., additional, Sutton, L.-A., additional, Plevova, K., additional, Mansouri, L., additional, Ljungstrom, V., additional, Ntoufa, S., additional, Davis, Z., additional, Juliusson, G., additional, Smedby, K. E., additional, Belessi, C., additional, Panagiotidis, P., additional, Touloumenidou, T., additional, Davi, F., additional, Langerak, A. W., additional, Ghia, P., additional, Strefford, J. C., additional, Oscier, D., additional, Mayer, J., additional, Stamatopoulos, K., additional, Pospisilova, S., additional, Rosenquist, R., additional, and Trbusek, M., additional

Published
2016
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29. Genomic disruption of the histone methyltransferase SETD2 in chronic lymphocytic leukaemia

Author

Parker, H, primary, Rose-Zerilli, M J J, additional, Larrayoz, M, additional, Clifford, R, additional, Edelmann, J, additional, Blakemore, S, additional, Gibson, J, additional, Wang, J, additional, Ljungström, V, additional, Wojdacz, T K, additional, Chaplin, T, additional, Roghanian, A, additional, Davis, Z, additional, Parker, A, additional, Tausch, E, additional, Ntoufa, S, additional, Ramos, S, additional, Robbe, P, additional, Alsolami, R, additional, Steele, A J, additional, Packham, G, additional, Rodríguez-Vicente, A E, additional, Brown, L, additional, McNicholl, F, additional, Forconi, F, additional, Pettitt, A, additional, Hillmen, P, additional, Dyer, M, additional, Cragg, M S, additional, Chelala, C, additional, Oakes, C C, additional, Rosenquist, R, additional, Stamatopoulos, K, additional, Stilgenbauer, S, additional, Knight, S, additional, Schuh, A, additional, Oscier, D G, additional, and Strefford, J C, additional

Published
2016
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30. Additional trisomies amongst patients with chronic lymphocytic leukemia carrying trisomy 12: the accompanying chromosome makes a difference

Author

Baliakas, P., primary, Puiggros, A., additional, Xochelli, A., additional, Sutton, L.-A., additional, Nguyen-Khac, F., additional, Gardiner, A., additional, Plevova, K., additional, Minga, E., additional, Hadzidimitriou, A., additional, Walewska, R., additional, McCarthy, H., additional, Ortega, M., additional, Collado, R., additional, Gonzalez, T., additional, Granada, I., additional, Luno, E., additional, Kota kova, J., additional, Moysiadis, T., additional, Davis, Z., additional, Stavroyianni, N., additional, Anagnostopoulos, A., additional, Strefford, J. C., additional, Pospisilova, S., additional, Davi, F., additional, Athanasiadou, A., additional, Rosenquist, R., additional, Oscier, D., additional, Espinet, B., additional, and Stamatopoulos, K., additional

Published
2016
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31. Recurrent mutations refine prognosis in chronic lymphocytic leukemia

Author

Baliakas, Panagiotis, Hadzidimitriou, A, Sutton, Lesley Ann, Rossi, D, Minga, E, Villamor, N, Larrayoz, M, Kminkova, J, Agathangelidis, A, Davis, Z, Tausch, E, Stalika, E, Kantorova, B, Mansouri, Larry, Scarfò, L, Cortese, Diego, Navrkalova, V, Rose-Zerilli, M J J, Smedby, K E, Juliusson, G, Anagnostopoulos, A, Makris, A M, Navarro, A, Delgado, J, Oscier, D, Belessi, C, Stilgenbauer, S, Ghia, P, Pospisilova, S, Gaidano, G, Campo, E, Strefford, J C, Stamatopoulos, Kostas, Rosenquist, Richard, Baliakas, Panagiotis, Hadzidimitriou, A, Sutton, Lesley Ann, Rossi, D, Minga, E, Villamor, N, Larrayoz, M, Kminkova, J, Agathangelidis, A, Davis, Z, Tausch, E, Stalika, E, Kantorova, B, Mansouri, Larry, Scarfò, L, Cortese, Diego, Navrkalova, V, Rose-Zerilli, M J J, Smedby, K E, Juliusson, G, Anagnostopoulos, A, Makris, A M, Navarro, A, Delgado, J, Oscier, D, Belessi, C, Stilgenbauer, S, Ghia, P, Pospisilova, S, Gaidano, G, Campo, E, Strefford, J C, Stamatopoulos, Kostas, and Rosenquist, Richard

Abstract

Through the European Research Initiative on chronic lymphocytic leukemia (CLL) (ERIC), we screened 3490 patients with CLL for mutations within the NOTCH1 (n=3334), SF3B1 (n=2322), TP53 (n=2309), MYD88 (n=1080) and BIRC3 (n=919) genes, mainly at diagnosis (75%) and before treatment (>90%). BIRC3 mutations (2.5%) were associated with unmutated IGHV genes (U-CLL), del(11q) and trisomy 12, whereas MYD88 mutations (2.2%) were exclusively found among M-CLL. NOTCH1, SF3B1 and TP53 exhibited variable frequencies and were mostly enriched within clinically aggressive cases. Interestingly, as the timespan between diagnosis and mutational screening increased, so too did the incidence of SF3B1 mutations; no such increase was observed for NOTCH1 mutations. Regarding the clinical impact, NOTCH1 mutations, SF3B1 mutations and TP53 aberrations (deletion/mutation, TP53ab) correlated with shorter time-to-first-treatment (P<0.0001) in 889 treatment-naive Binet stage A cases. In multivariate analysis (n=774), SF3B1 mutations and TP53ab along with del(11q) and U-CLL, but not NOTCH1 mutations, retained independent significance. Importantly, TP53ab and SF3B1 mutations had an adverse impact even in U-CLL. In conclusion, we support the clinical relevance of novel recurrent mutations in CLL, highlighting the adverse impact of SF3B1 and TP53 mutations, even independent of IGHV mutational status, thus underscoring the need for urgent standardization/harmonization of the detection methods., De tre sista författarna delar sistaförfattarskapet.

Published
2015
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32. REFINING PROGNOSIS OF CHRONIC LYMPHOCYTIC LEUKEMIA WITH SOMATICALLY HYPERMUTATED B-CELL RECEPTORS : A NOVEL PROGNOSTIC INDEX ON BEHALF OF THE EUROPEAN RESEARCH INITIATIVE ON CLL (ERIC)

Author

Baliakas, Panagiotis, Hadzidimitriou, A., Mattsson, Mattias, Xochelli, Aliki, Sutton, L. A., Minga, E., Scarfo, L., Rossi, D., Davis, Z., Agathangelidis, A., Villamor, N., Parker, H., Kotaskova, J., Stalika, E., Plevova, K., Mansouri, Larry, Cortese, Diego, Navarro Lopez, A., Delgado, J., Larrayoz, M., Anagnostopoulos, A., Belessi, C., Smedby, K. E., Juliusson, G., Strefford, J. C., Pospisilova, S., Oscier, D., Gaidano, G., Campo, E., Ghia, P., Rosenquist, Richard, Stamatopoulos, Kostas, Baliakas, Panagiotis, Hadzidimitriou, A., Mattsson, Mattias, Xochelli, Aliki, Sutton, L. A., Minga, E., Scarfo, L., Rossi, D., Davis, Z., Agathangelidis, A., Villamor, N., Parker, H., Kotaskova, J., Stalika, E., Plevova, K., Mansouri, Larry, Cortese, Diego, Navarro Lopez, A., Delgado, J., Larrayoz, M., Anagnostopoulos, A., Belessi, C., Smedby, K. E., Juliusson, G., Strefford, J. C., Pospisilova, S., Oscier, D., Gaidano, G., Campo, E., Ghia, P., Rosenquist, Richard, and Stamatopoulos, Kostas

Published
2015

33. SNP-Arrays Provide New Insights Into the Pathogenesis of Richter Syndrome

Author

Rinaldi, A., Chigrinova, E., Kwee, I., Rossi, D., Rancoita, P. M. V., Strefford, J. C., Oscier, D. G., Stamatopoulos, K., Papadaki, T., Berger, F., Young, K. H., Murray, F., Rosenquis, R., Greiner, T. C., Chan, W. C., Arcaini, L., Lucioni, M., Marasca, R., Inghirami, G., Ladetto, M., Forconi, F., Cogliatti, S., Votavova, H., Swerdlow, S. H., Stilgenbauer, S., Piris, M., Matolcsy, A., Spagnolo, D., Nikitin, E., Zamo', Alberto, Gattei, V., Pasqualucci, L., Zucca, E., Gaidano, G., and Bertoni, F.

Subjects
SNP-Arrays, B-CLL, Richter Syndrome
Published
2011

34. The SF3B1 inhibitor spliceostatin A (SSA) elicits apoptosis in chronic lymphocytic leukaemia cells through downregulation of Mcl-1

Author

Larrayoz, M, primary, Blakemore, S J, additional, Dobson, R C, additional, Blunt, M D, additional, Rose-Zerilli, M J J, additional, Walewska, R, additional, Duncombe, A, additional, Oscier, D, additional, Koide, K, additional, Forconi, F, additional, Packham, G, additional, Yoshida, M, additional, Cragg, M S, additional, Strefford, J C, additional, and Steele, A J, additional

Published
2015
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35. Low frequency mutations independently predict poor treatment-free survival in early stage chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis

Author

Winkelmann, N., primary, Rose-Zerilli, M., additional, Forster, J., additional, Parry, M., additional, Parker, A., additional, Gardiner, A., additional, Davies, Z., additional, Steele, A. J., additional, Parker, H., additional, Cross, N. C. P., additional, Oscier, D. G., additional, and Strefford, J. C., additional

Published
2015
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37. ATM mutation rather than BIRC3 deletion and/or mutation predicts reduced survival in 11q-deleted chronic lymphocytic leukemia: data from the UK LRF CLL4 trial

Author

Rose-Zerilli, M. J. J., primary, Forster, J., additional, Parker, H., additional, Parker, A., additional, Rodriguez, A. E., additional, Chaplin, T., additional, Gardiner, A., additional, Steele, A. J., additional, Collins, A., additional, Young, B. D., additional, Skowronska, A., additional, Catovsky, D., additional, Stankovic, T., additional, Oscier, D. G., additional, and Strefford, J. C., additional

Published
2014
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38. Distinct patterns of novel gene mutations in poor-prognostic stereotyped subsets of chronic lymphocytic leukemia : the case of SF3B1 and subset #2

Author

Strefford, J. C., Sutton, Lesley Ann, Baliakas, Panagiotis, Agathangelidis, A., Malcikova, J., Plevova, K., Scarfo, L., Davis, Z., Stalika, E., Cortese, Diego, Cahill, Nicola, Pedersen, L. B., di Celle, P. F., Tzenou, T., Geisler, C., Panagiotidis, P., Langerak, A. W., Chiorazzi, N., Pospisilova, S., Oscier, D., Davi, F., Belessi, C., Mansouri, Larry, Ghia, P., Stamatopoulos, K., Rosenquist, Richard Brandell, Strefford, J. C., Sutton, Lesley Ann, Baliakas, Panagiotis, Agathangelidis, A., Malcikova, J., Plevova, K., Scarfo, L., Davis, Z., Stalika, E., Cortese, Diego, Cahill, Nicola, Pedersen, L. B., di Celle, P. F., Tzenou, T., Geisler, C., Panagiotidis, P., Langerak, A. W., Chiorazzi, N., Pospisilova, S., Oscier, D., Davi, F., Belessi, C., Mansouri, Larry, Ghia, P., Stamatopoulos, K., and Rosenquist, Richard Brandell

Abstract

Recent studies have revealed recurrent mutations of the NOTCH1, SF3B1 and BIRC3 genes in chronic lymphocytic leukemia (CLL), especially among aggressive, chemorefractory cases. Nevertheless, it is currently unknown whether their presence may differ in subsets of patients carrying stereotyped B-cell receptors and also exhibiting distinct prognoses. Here, we analyzed the mutation status of NOTCH1, SF3B1 and BIRC3 in three subsets with particularly poor prognosis, that is, subset # 1, # 2 and # 8, aiming to explore links between genetic aberrations and immune signaling. A remarkably higher frequency of SF3B1 mutations was revealed in subset # 2 (44%) versus subset # 1 and # 8 (4.6% and 0%, respectively; P<0.001). In contrast, the frequency of NOTCH1 mutations in subset # 2 was only 8%, lower than the frequency observed in either subset # 1 or # 8 (19% and 14%, respectively; P 0.04 for subset # 1 versus # 2). No associations were found for BIRC3 mutations that overall were rare. The apparent non-random association of certain mutations with stereotyped CLL subsets alludes to subset-biased acquisition of genomic aberrations, perhaps consistent with particular antigen/antibody interactions. These novel findings assist in unraveling specific mechanisms underlying clinical aggressiveness in poor-prognostic stereotyped subsets, with far-reaching implications for understanding their clonal evolution and implementing biologically oriented therapy., De tre första författarna delar första författarskapet.

Published
2013
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39. Whole-exome sequencing in splenic marginal zone lymphoma reveals mutations in genes involved in marginal zone differentiation

Author

Martínez, N, primary, Almaraz, C, additional, Vaqué, J P, additional, Varela, I, additional, Derdak, S, additional, Beltran, S, additional, Mollejo, M, additional, Campos-Martin, Y, additional, Agueda, L, additional, Rinaldi, A, additional, Kwee, I, additional, Gut, M, additional, Blanc, J, additional, Oscier, D, additional, Strefford, J C, additional, Martinez-Lopez, J, additional, Salar, A, additional, Sole, F, additional, Rodriguez-Peralto, J L, additional, Diez-Tascón, C, additional, García, J F, additional, Fraga, M, additional, Sebastián, E, additional, Alvés, J, additional, Menárguez, J, additional, González-Carreró, J, additional, Casado, L F, additional, Bayes, M, additional, Bertoni, F, additional, Gut, I, additional, and Piris, M A, additional

Published
2013
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40. EGR2mutations define a new clinically aggressive subgroup of chronic lymphocytic leukemia

Author

Young, E, Noerenberg, D, Mansouri, L, Ljungström, V, Frick, M, Sutton, L-A, Blakemore, S J, Galan-Sousa, J, Plevova, K, Baliakas, P, Rossi, D, Clifford, R, Roos-Weil, D, Navrkalova, V, Dörken, B, Schmitt, C A, Smedby, K E, Juliusson, G, Giacopelli, B, Blachly, J S, Belessi, C, Panagiotidis, P, Chiorazzi, N, Davi, F, Langerak, A W, Oscier, D, Schuh, A, Gaidano, G, Ghia, P, Xu, W, Fan, L, Bernard, O A, Nguyen-Khac, F, Rassenti, L, Li, J, Kipps, T J, Stamatopoulos, K, Pospisilova, S, Zenz, T, Oakes, C C, Strefford, J C, Rosenquist, R, and Damm, F

Abstract

Recurrent mutations within EGR2were 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 EGR2hotspot 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. EGR2mutations 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 ATMlesions (42%), TP53aberrations (18%) and NOTCH1/FBXW7mutations (16%). EGR2mutations 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 TP53aberrations. In summary, EGR2mutations were independently associated with an unfavorable prognosis, comparable to CLL patients carrying TP53aberrations, suggesting that EGR2-mutated patients represent a new patient subgroup with very poor outcome.

Published
2017
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46. Molecular characterisation of the t(1;15)(p22;q22) translocation in the prostate cancer cell line LNCaP.

Author

Strefford, J. C., Lane, T. M., Hill, A., LeRoux, L., Foot, N. J., Shipley, J., Oliver, R. T. D., Lu, Y.-J., and Young, B. D.

Subjects
*PROSTATE cancer, *CHROMOSOMAL translocation, *CANCER genetics, *MOLECULAR genetics, *GENETICS, *CHROMOSOMES
Abstract

Although chromosome translocations are well-documented recurrent events in hematological malignancies and soft tissue sarcomas, their significance in carcinomas is less clear. We report here the molecular characterization of the reciprocal translocation t(1;15)(p22;q22) in the prostate carcinoma cell line, LNCaP. The chromosome 1 breakpoint was localized to a single BAC clone, RP11-290M5, by sequential FISH analysis of clones selected from the NCBI chromosome 1 map. This was further refined to a 580-bp region by Southern blot analysis. A 2.85-kb fragment spanning the der(1) breakpoint was amplified by long-range inverse PCR. The breakpoint on chromosome 1 was shown to lie between the CYR61 and the DDAH1 genes with the der(1) junctional sequence linking the CYR61 gene to the TSPAN3 (TM4SF8) gene on chromosome 15. Confirmatory PCR and FISH mapping of the der(15) showed loss of chromosome material proximal to the breakpoint on chromosome 15, containing the PSTPIP1 and RCN2 genes. On the available evidence we conclude that this translocation does not result in an in-frame gene fusion. Comparative expressed sequence hybridization (CESH) and comparative genomic hybridization (CGH) analysis, showed relative down-regulation of gene expression surrounding the breakpoint, but no gross change in genomic copy number. Real-time quantitative RT-PCR for genes around the breakpoint supported the CESH data. Therefore, here we may have revealed a gene down-regulation mechanism associated with a chromosome translocation, either through small deletion at the breakpoint or through another means of chromosome domain related gene regulation. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Published
2006
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47. The characterisation of the lymphoma cell line U937, using comparative genomic hybridisation and multi-plex FISH.

Author

Strefford, J. C., Foot, N. J., Chaplin, T., Neat, M. J., Oliver, R. T. D., Young, B. D., and Jones, L. K.

Subjects
*CELL lines, *LYMPHOMAS, *MYELOID leukemia, *CYTOGENETICS, *DROSOPHILA, *KARYOTYPES
Abstract

The cell line U937, which has been used extensively for studies of myeloid differentiation, bears the t(10;11)(p13;q14) translocation which results in a fusion between the MLLT10 (myeloid/lymphoid or mixed-lineage leukemia [trithorax, Drosophila, homolog]; translocated to 10; alias AF10) gene and the Ap-3-like clathrin assembly protein, PICALM (Clathrin assembly lymphoid myeloid leukaemia). Apart from this translocation, very little is known about the other genetic alterations in this cell line that may represent significant events in disease progression. In this study, conventional G-banding, CGH and M-FISH have been used to characterise fully all of the cytogenetic alterations present in the U937 cell line. M-FISH analysis confirmed the presence of the t(10;11) and an apparently normal copy of both chromosomes 10 and 11. A t(1;5) translocation was observed as well as several unbalanced rearrangements. CGH detected amplifications resulting from duplications of 2q, 6p and 13q. These changes could result in fusion gene products involved in carcinogenesis or the positions of putative oncogenes and tumour suppressor genes. A good correlation between conventional G-banding, CGH and M-FISH was observed. Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Published
2001
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49. REFINING PROGNOSIS OF CHRONIC LYMPHOCYTIC LEUKEMIA WITH SOMATICALLY HYPERMUTATED B-CELL RECEPTORS: A NOVEL PROGNOSTIC INDEX ON BEHALF OF THE EUROPEAN RESEARCH INITIATIVE ON CLL (ERIC)

Author

Baliakas, P., Hadzidimitriou, A., Mattsson, M., Xochelli, A., Sutton, L. A., Minga, E., Scarfo, L., Rossi, D., Davis, Z., Agathangelidis, A., Villamor, N., Parker, H., Kotaskova, J., Stalika, E., Plevova, K., Mansouri, L., Cortese, D., Navarro Lopez, A., Delgado, J., Larrayoz, M., Anagnostopoulos, A., Belessi, C., Smedby, K. E., Juliusson, G., Strefford, J. C., Sarka Pospisilova, Oscier, D., Gaidano, G., Campo, E., Ghia, P., Rosenquist, R., and Stamatopoulos, K.

50. A Comparison of Array-based Comparative Genomic Hybridization (aCGH) Platforms in the Accurate Characterization of Cytogenetic Alteration Is Multiple.

Author

Worley, Helen, Cheung, K. L., Harrison, C. J., and Strefford, J. C.

Subjects
MULTIPLE myeloma
Abstract

Presents an abstract of the article "A Comparison of Array-based Comparative Genomic Hybridization (aCGH) Platforms in the Accurate Characterization of Cytogenetic Alterations Is Multiple Myeloma," by Helen Worley, K. L. Cheung, C. J. Harrison, and J. C. Strefford.

Published
2005

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