Alterations of the Cell-Cycle Inhibitors p27KIP1 and p16INK4a Are Frequent in Blastic Plasmacytoid Dendritic Cell Neoplasms  Thomas Wiesner, Anna C. Obenauf,

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Alterations of the Cell-Cycle Inhibitors p27KIP1 and p16INK4a Are Frequent in Blastic Plasmacytoid Dendritic Cell Neoplasms  Thomas Wiesner, Anna C. Obenauf, Carlo Cota, Isabella Fried, Michael R. Speicher, Lorenzo Cerroni  Journal of Investigative Dermatology  Volume 130, Issue 4, Pages 1152-1157 (April 2010) DOI: 10.1038/jid.2009.369 Copyright © 2010 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Genomic aberrations in BPDCN detected by array CGH. (a) The ideogram summarizes chromosomal gains and losses of 14 patients. The green and red bars on the right side of each chromosome indicate how often, that is, in what percentage, copy number changes were found. Losses are displayed in green in the left half of each figure, and gains are shown in red in the right half. Deletions at chromosomes 9, 12, 13, 15, and 19 were most often observed, whereas other changes only occurred in a low percentage of cases. (b) Representative genome-wide array-CGH profile of case 1. On the x axis, the data are organized along the 22 autosomal chromosomes and the 2 sex chromosomes. The y axis shows the relative copy number on a logarithmic scale. The blue bars define losses on chromosome 1, 6, 9, 12, 13. Abbreviations: BPDCN, blastic plasmacytoid dendritic cell neoplasm; CGH, comparative genomic hybridization. Journal of Investigative Dermatology 2010 130, 1152-1157DOI: (10.1038/jid.2009.369) Copyright © 2010 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Losses of chromosomes 9 and 12 in detail. (a) The common deleted region on chromosome 12, detected in 64% of cases, is only 1.6Mb large, and contains the CDKN1B gene. The right part of this figure shows the array-CGH profile of case 1. The blue line follows a log ratio of 0 over large parts of chromosome 12, indicating a normal copy number, but becomes negative at 12p13 (log ratio of -1), pointing at a monoallelic loss of this region. The shaded blue area defines the lost region. (b) Losses on chromosome 9 were detected in 50% of cases. The right part of this figure illustrates a biallelic, 500kb sized deletion at 9p21.3 (case 8). The blue line shows the log ratio and indicates at -1, a monoallelic loss of the whole chromosome 9; values <-2 indicate an additional loss of the CDKN2A–ARF–CDKN2B locus of the second chromosome. (c) Immunostaining of case 8 shows a weak expression of p27KIP1 in the nuclei of tumor cells, but also scattered admixed malignant cells with a strong nuclear p27KIP1 expression. Bar=10μm. (d) Immunostaining for p16INK4a was constantly negative as shown herein in case 7. Bar=10μm. Abbreviation: CGH, comparative genomic hybridization. Journal of Investigative Dermatology 2010 130, 1152-1157DOI: (10.1038/jid.2009.369) Copyright © 2010 The Society for Investigative Dermatology, Inc Terms and Conditions