Fine-mapping chromosomal loss at 9p21: Correlation with prognosis in primary cutaneous diffuse large B-cell lymphoma, leg type

Nancy J. Senff, Willem H. Zoutman, Maarten H. Vermeer, Chalid Assaf, Emilio Berti, Lorenzo Cerroni, Blanca Espinet, Ricardo Fernandez De Misa Cabrera, Marie Louise Geerts, Werner Kempf, Tracey J. Mitchell, Marco Paulli, Tony Petrella, Nicola Pimpinelli, Marco Santucci, Sean J. Whittaker, Rein Willemze, Cornelis P. Tensen

Research output: Contribution to journalArticle

Abstract

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL, LT) is the most aggressive type of primary cutaneous B-cell lymphoma. In a recent study on 12 patients it was found that inactivation of CDKN2A by either deletion of 9p21.3 or promoter hypermethylation is correlated with a worse prognosis. In the present EORTC multicenter study, skin biopsies of 64 PCLBCL, LT patients were analyzed by multiplex ligation-dependent probe amplification to validate these previous results and to fine-map the losses in this region. Although no minimal common region of loss could be identified, most homozygous loss was observed in the CDKN2A gene (43 of 64; 67%) encoding p16 and p14ARF. Promoter hypermethylation of p16 and p14ARF was found in six and zero cases, respectively. Survival was markedly different between patients with versus without aberrations in the CDKN2A gene (5-year disease-specific survival 43 versus 70%; P=0.06). In conclusion, our results confirm that deletion of chromosome 9p21.3 is found in a considerable proportion of PCLBCL, LT patients and that inactivation of the CDKN2A gene is associated with an unfavorable prognosis. In most patients the deletion involves a large area of at least several kilobase pairs instead of a small minimal common region.

Original languageEnglish
Pages (from-to)1149-1155
Number of pages7
JournalJournal of Investigative Dermatology
Volume129
Issue number5
DOIs
Publication statusPublished - May 2009

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

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    Senff, N. J., Zoutman, W. H., Vermeer, M. H., Assaf, C., Berti, E., Cerroni, L., Espinet, B., De Misa Cabrera, R. F., Geerts, M. L., Kempf, W., Mitchell, T. J., Paulli, M., Petrella, T., Pimpinelli, N., Santucci, M., Whittaker, S. J., Willemze, R., & Tensen, C. P. (2009). Fine-mapping chromosomal loss at 9p21: Correlation with prognosis in primary cutaneous diffuse large B-cell lymphoma, leg type. Journal of Investigative Dermatology, 129(5), 1149-1155. https://doi.org/10.1038/jid.2008.357