Hahtola Sonja, Burghart Elke, Puputti Marjut, Karenko Leena, Abdel-Rahman Wael M, Väkevä Liisa, Jeskanen Leila, Virolainen Susanna, Karvonen Jaakko, Salmenkivi Kaisa, Kinnula Vuokko, Joensuu Heikki, Peltomäki Päivi, Klein Christoph A, Ranki Annamari
Department of Dermatology and Allergology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
Genes Chromosomes Cancer. 2008 Feb;47(2):107-17. doi: 10.1002/gcc.20513.
Cutaneous T-cell lymphoma (CTCL) patients have an increased risk of certain secondary cancers, the most common of which are lung cancers, especially small cell lung cancer. To reveal the molecular pathogenesis underlying CTCL-associated lung cancer, we analyzed genomic aberrations in CTCL-associated and reference lung cancer samples. DNA derived from microdissected lung cancer cells of five CTCL-associated lung cancers and five reference lung cancers without CTCL association was analyzed by comparative genomic hybridization (CGH). Fluorescent in situ hybridization (FISH), immunohistochemistry (IHC), and loss of heterozygosity (LOH) analysis were performed for selected genes. In CTCL-associated lung cancer, CGH revealed chromosomal aberrations characterizing both lung cancer and CTCL, but also losses of 1p, and 19, and gains of 4q and 7, hallmarks of CTCL. LOH for the CTCL-associated NAV3 gene was detected in two of the four informative primary lung cancers. FISH revealed increased copy number of the KIT gene in 3/4 of CTCL-associated lung cancers and 1/5 of primary lung cancers. PDGFRA and VEGFR2 copy numbers were also increased. IHC showed moderate KIT expression when the gene copy number was increased. CTCL-associated lung cancer shows chromosomal aberrations different from primary lung cancer, especially amplifications of 4q, a chromosome arm frequently deleted in the latter tumor type. Copy numbers and expression of selected genes in chromosome 4 differed between CTCL-associated and reference lung cancers. These preliminary observations warrant further prospective studies to identify the common underlying factors between CTCL and CTCL-associated lung cancer.
皮肤T细胞淋巴瘤（CTCL）患者患某些继发性癌症的风险增加，其中最常见的是肺癌，尤其是小细胞肺癌。为了揭示CTCL相关肺癌的分子发病机制，我们分析了CTCL相关肺癌样本和对照肺癌样本中的基因组畸变。通过比较基因组杂交（CGH）分析了来自5例CTCL相关肺癌和5例无CTCL关联的对照肺癌的显微切割肺癌细胞的DNA。对选定基因进行了荧光原位杂交（FISH）、免疫组织化学（IHC）和杂合性缺失（LOH）分析。在CTCL相关肺癌中，CGH揭示了表征肺癌和CTCL的染色体畸变，同时也发现了1p和19号染色体的缺失以及4q和7号染色体的增加，这些都是CTCL的特征。在4例信息丰富的原发性肺癌中有2例检测到CTCL相关NAV3基因的杂合性缺失。FISH显示，3/4的CTCL相关肺癌和1/5的原发性肺癌中KIT基因的拷贝数增加。PDGFRA和VEGFR2的拷贝数也增加。当基因拷贝数增加时，IHC显示KIT表达中等。CTCL相关肺癌显示出与原发性肺癌不同的染色体畸变，尤其是4q的扩增，而4q染色体臂在后者肿瘤类型中经常缺失。CTCL相关肺癌和对照肺癌之间，4号染色体上选定基因的拷贝数和表达存在差异。这些初步观察结果需要进一步的前瞻性研究，以确定CTCL和CTCL相关肺癌之间的共同潜在因素。
