Kluiver Joost, Kok Klaas, Pfeil Ines, de Jong Debora, Blokzijl Tjasso, Harms Geert, van der Vlies Pieter, Diepstra Arjan, Atayar Ciğdem, Poppema Sibrand, Küppers Ralf, van den Berg Anke
Department of Pathology and Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Hematol Oncol. 2007 Mar;25(1):21-9. doi: 10.1002/hon.804.
To identify genes involved in the pathogenesis of classical Hodgkin lymphoma (cHL), we performed serial analysis of gene expression (SAGE) and array-based comparative genomic hybridization (aCGH). Comparison of SAGE libraries of cHL cell lines L428 and L1236 with that of germinal centre B cells revealed consistent overexpression of only 14 genes. In contrast, 141 genes were downregulated in both cHL cell lines, including many B cell and HLA genes. aCGH revealed gain of 2p, 7p, 9p, 11q and Xq and loss of 4q and 11q. Eighteen percent of the differentially expressed genes mapped to regions with loss or gain and a good correlation was observed between underexpression and loss or overexpression and gain of DNA. Remarkably, gain of 2p and 9p did not correlate with increased expression of the proposed target genes c-REL and JAK2. Downregulation of many genes within the HLA region also did not correlate with loss of DNA. FSCN1 and IRAK1 mapping at genomic loci (7p and Xq) that frequently showed gain were overexpressed in cHL cell lines and might be involved in the pathogenesis of cHL.
为了鉴定参与经典型霍奇金淋巴瘤（cHL）发病机制的基因，我们进行了基因表达系列分析（SAGE）和基于芯片的比较基因组杂交（aCGH）。将cHL细胞系L428和L1236的SAGE文库与生发中心B细胞的SAGE文库进行比较，结果显示只有14个基因持续高表达。相比之下，在这两种cHL细胞系中，有141个基因表达下调，其中包括许多B细胞和HLA基因。aCGH结果显示存在2p、7p、9p、11q和Xq的扩增以及4q和11q的缺失。18%的差异表达基因定位于存在缺失或扩增的区域，并且在基因低表达与DNA缺失或高表达与DNA扩增之间观察到良好的相关性。值得注意的是，2p和9p的扩增与推测的靶基因c-REL和JAK2的表达增加并无关联。HLA区域内许多基因的下调也与DNA缺失无关。定位于经常出现扩增的基因组位点（7p和Xq）的FSCN1和IRAK1在cHL细胞系中高表达，并可能参与cHL的发病机制。
