Large but not small copy-number alterations correlate to high-risk genomic aberrations and survival in chronic lymphocytic leukemia: a high-resolution genomic screening of newly diagnosed patients (original) (raw)

Leukemia volume 24, pages 211–215 (2010)Cite this article

The known recurrent genomic aberrations, that is deletions of 11q, 13q, 17p and trisomy 12, are important prognostic markers, which reliably predict clinical outcome in chronic lymphocytic leukemia (CLL) patients.1 Approximately 50% of CLL patients carry deletions of 13q, which is correlated with an indolent disease course when detected as a sole aberration. In contrast, deletions of 11q and 17p, which cover the ATM and TP53 gene, respectively, are associated with poor prognosis. Furthermore, trisomy 12 is related to an intermediate prognosis, whereas deletion of 6q has been identified as a recurrent CLL progression marker.1, 2

Genomic microarrays are widely used for screening of copy-number alterations (CNAs) in cancers. Several studies on CLL have provided additional information on genome-wide alterations, such as gain of 2p and deletion of 22q.3, 4 Recently, an SNP-array (50K) study showed an association between genomic complexity (⩾3 CNAs/sample) and time to first or second treatment as clinical end points.5 To date, copy-number neutral loss of heterozygosity has been identified on chromosome 11p, 13q, and 17p in CLL,3, 6 although the biological or clinical significance remains unknown.

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References

  1. Dohner H, Stilgenbauer S, Benner A, Leupolt E, Krober A, Bullinger L et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med 2000; 343: 1910–1916.
    Article CAS Google Scholar
  2. Finn WG, Kay NE, Kroft SH, Church S, Peterson LC . Secondary abnormalities of chromosome 6q in B-cell chronic lymphocytic leukemia: a sequential study of karyotypic instability in 51 patients. Am J Hematol 1998; 59: 223–229.
    Article CAS Google Scholar
  3. Pfeifer D, Pantic M, Skatulla I, Rawluk J, Kreutz C, Martens UM et al. Genome-wide analysis of DNA copy number changes and LOH in CLL using high-density SNP arrays. Blood 2007; 109: 1202–1210.
    Article CAS Google Scholar
  4. Gunn SR, Bolla AR, Barron LL, Gorre ME, Mohammed MS, Bahler DW et al. Array CGH analysis of chronic lymphocytic leukemia reveals frequent cryptic monoallelic and biallelic deletions of chromosome 22q11 that include the PRAME gene. Leuk Res 2008; 33: 1276–1281.
    Article Google Scholar
  5. Kujawski L, Ouillette P, Erba H, Saddler C, Jakubowiak A, Kaminski M et al. Genomic complexity identifies patients with aggressive chronic lymphocytic leukemia. Blood 2008; 112: 1993–2003.
    Article CAS Google Scholar
  6. Lehmann S, Ogawa S, Raynaud SD, Sanada M, Nannya Y, Ticchioni M et al. Molecular allelokaryotyping of early-stage, untreated chronic lymphocytic leukemia. Cancer 2008; 112: 1296–1305.
    Article CAS Google Scholar
  7. Smedby KE, Hjalgrim H, Melbye M, Torrang A, Rostgaard K, Munksgaard L et al. Ultraviolet radiation exposure and risk of malignant lymphomas. J Natl Cancer Inst 2005; 97: 199–209.
    Article Google Scholar
  8. Gunnarsson R, Staaf J, Jansson M, Ottesen AM, Goransson H, Liljedahl U et al. Screening for copy-number alterations and loss of heterozygosity in chronic lymphocytic leukemia-a comparative study of four differently designed, high resolution microarray platforms. Genes Chromosomes Cancer 2008; 47: 697–711.
    Article CAS Google Scholar
  9. Grubor V, Krasnitz A, Troge JE, Meth JL, Lakshmi B, Kendall JT et al. Novel genomic alterations and clonal evolution in chronic lymphocytic leukemia revealed by representational oligonucleotide microarray analysis (ROMA). Blood 2009; 113: 1294–1303.
    Article CAS Google Scholar
  10. Goransson H, Edlund K, Rydaker M, Rasmussen M, Winquist J, Ekman S et al. Quantification of normal cell fraction and copy number neutral LOH in clinical lung cancer samples using SNP array data. PloS One 2009; 4: e6057.
    Article Google Scholar

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Acknowledgements

We thank the Swedish CLL group for support during the collection of clinical data. This research was supported by the Nordic Cancer Union, the Swedish Cancer Society, the Swedish Research Council, Lion's Cancer Research Foundation, Uppsala, Sweden and the Svend Andersen Foundation, Denmark. A fellowship (2006/18) was awarded to R Rosenquist by the European Hematology Association.

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Author notes

  1. G Juliusson and R Rosenquist: These two authors contributed equally to this work.

Authors and Affiliations

  1. Department of Laboratory Medicine, Stem Cell Center, Hematology and Transplantation, Lund University, Lund, Sweden
    R Gunnarsson, K Karlsson & G Juliusson
  2. Department of Medical Sciences, Cancer Pharmacology and Informatics, Uppsala University, Uppsala, Sweden
    A Isaksson, H Göransson & M Rasmussen
  3. Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden
    M Mansouri, M Jansson, N Cahill & R Rosenquist
  4. Department of Oncology, Clinical Sciences, Lund University, Lund, Sweden
    J Staaf
  5. Departments of Hematology/Oncology, Karolinska University Hospital, Stockholm, Sweden
    J Lundin
  6. Department of Hematology, Karolinska University Hospital, Stockholm, Sweden
    S Norin
  7. Department of Hematology, Leukemia Laboratory, Rigshospitalet, Copenhagen, Denmark
    A M Buhl & J Jurlander
  8. Department of Medicine, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden
    K E Smedby
  9. Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
    H Hjalgrim

Authors

  1. A Isaksson
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  2. M Mansouri
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  3. H Göransson
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  4. M Jansson
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  5. N Cahill
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  6. M Rasmussen
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  7. J Staaf
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  8. J Lundin
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  9. S Norin
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  10. A M Buhl
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  11. K E Smedby
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  12. H Hjalgrim
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  13. K Karlsson
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  14. J Jurlander
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  15. G Juliusson
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  16. R Rosenquist
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Corresponding author

Correspondence toR Gunnarsson.

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Gunnarsson, R., Isaksson, A., Mansouri, M. et al. Large but not small copy-number alterations correlate to high-risk genomic aberrations and survival in chronic lymphocytic leukemia: a high-resolution genomic screening of newly diagnosed patients.Leukemia 24, 211–215 (2010). https://doi.org/10.1038/leu.2009.187

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