Catrin Youssif and Jan Goldenbogen contributed equally to this work.
Genomic profiling of pediatric ALK-positive anaplastic large cell lymphoma: A Children's Cancer and Leukaemia Group Study
Article first published online: 18 AUG 2009
Copyright © 2009 Wiley-Liss, Inc.
Genes, Chromosomes and Cancer
Volume 48, Issue 11, pages 1018–1026, November 2009
How to Cite
Youssif, C., Goldenbogen, J., Hamoudi, R., Carreras, J., Viskaduraki, M., Cui, Y.-x., Bacon, C. M., Burke, G. A. A. and Turner, S. D. (2009), Genomic profiling of pediatric ALK-positive anaplastic large cell lymphoma: A Children's Cancer and Leukaemia Group Study. Genes Chromosom. Cancer, 48: 1018–1026. doi: 10.1002/gcc.20701
- Issue published online: 10 SEP 2009
- Article first published online: 18 AUG 2009
- Manuscript Accepted: 15 JUL 2009
- Manuscript Received: 11 MAY 2009
- The Leukaemia Research Fund (UK)
- The Kay Kendall Leukaemia Fund
- Cancer Research UK
- The Health Foundation/The Royal College of Pathologists/The Pathological Society of Great Britain and Ireland
- The Leonardo Da Vinci Fund, EU Programme
Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) is a T-cell malignancy in which ALK expression is a consequence of the t(2;5) or a variant translocation involving Chromosome 2. For the most part, this disease presents in the pediatric population and most, but not all, patients are successfully treated. Although the t(2;5) product nucleophosmin-ALK has been extensively studied for its transforming properties, very little is known regarding cooperative genetic mutations that may contribute to lymphomagenesis and may predict survival outcome, specifically in a purely pediatric population. We set out to determine the frequency and positions of genomic imbalances in this relatively rare disease. We collected biopsy material from 15 UK-resident children with ALK-expressing ALCL. We performed array comparative genomic hybridization at a resolution of 1 MB using DNA isolated from tumor tissue. Some of the more common genomic gains were confirmed by quantitative PCR. Regions of genomic gain were far more common than losses and were most often detected on chromosomes 1–4, 5–12, 14, and 17, with Chromosome 11 being the most frequent site of genomic imbalances. Patients with 14 or fewer imbalances had a lower overall 3-year survival (87.5–40%, P = 0.14) as did patients with gains in the regions of DDB1 or BIRC5. A range of genomic imbalances exist in ALK-expressing ALCL of a pediatric origin, with a greater number associated with poorer overall survival. © 2009 Wiley-Liss, Inc.