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Lymphoma

Genome-wide detection of recurring sites of uniparental disomy in follicular and transformed follicular lymphoma

Leukemia volume 21, pages 1514–1520 (2007)Cite this article

Abstract

Single-nucleotide polymorphism (SNP) array analysis was performed using the 10K GeneChip array on a series of 26 paired follicular lymphoma (FL) and transformed-FL (t-FL) biopsies and the lymphoma cell lines SCI-1, DoHH2 and RL2261. Regions of acquired homozygosity were detected in 43/52 (83%) primary specimens with a mean of 1.7 and 3.0 aberrations in the FL and t-FL, respectively. A notable feature was the occurrence of recurring sites of acquired uniparental disomy (aUDP) on 6p, 9p, 12q and 17p in cell lines and primary samples. Homozygosity of 9p and 17p arose predominantly in t-FL and in three cases rendered the cell homozygous for a pre-existing mutation of either CDKN2A or TP53. These data suggest that mutation precedes mitotic recombination, which leads to the removal of the remaining wild-type allele. In all, 18 cases exhibited abnormalities in both FL and t-FL samples. In 10 cases blocks of homozygosity were detected in FL that were absent in the subsequent t-FL sample. These differences support the notion that FL and t-FL may arise in a proportion of patients by divergence from a common malignant ancestor cell rather than by clonal evolution from an antecedent FL.

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Acknowledgements

We thank Randy Gascoyne for sharing his unpublished flow data in FL, Susan Weiss for assistance in preparing the article, Iram Gull and Victoria Miller for sample collection and storage, and Jean-Baptiste Cazier and Manu Gupta for helpful comments on the article. Derville O’Shea is a MRC training fellow and Emanuela Carlotti is a Bart's and the Royal London Charitable Foundation fellow. The work was also supported by the Cancer Research UK and Kay Kendall Leukaemia Fund.

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Authors and Affiliations

  1. Cancer Research UK, Centre for Medical Oncology, Barts and the London School of Medicine and Dentistry, London, UK

    J Fitzgibbon, S Iqbal, A Davies, D O'Shea, E Carlotti, T Chaplin, J Matthews, M Raghavan, T A Lister & B D Young

  2. Department of Histopathology, St Bartholomew's Hospital, London, UK

    A Norton

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Correspondence to J Fitzgibbon.

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Supplementary Information accompanies the paper on the National Centre for Biotechnology Information website (http://www.ncbi.nlm.nih.gov/projects/geo/query/acc.cgi?acc=GSE7425)

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Fitzgibbon, J., Iqbal, S., Davies, A. et al. Genome-wide detection of recurring sites of uniparental disomy in follicular and transformed follicular lymphoma. Leukemia 21, 1514–1520 (2007). https://doi.org/10.1038/sj.leu.2404696

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