Array comparative genomic hybridization reveals distinct DNA copy number differences between gastrointestinal stromal tumors and leiomyosarcomas
Array comparative genomic hybridization reveals distinct DNA copy number differences between gastrointestinal stromal tumors and leiomyosarcomas
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DOI：
10.1158/0008-5472.can-06-1972
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发表时间：
2006-09-15
期刊：
影响因子：
11.2
通讯作者：
Myklebost, Ola
中科院分区：
文献类型：
--
作者：
Meza-Zepeda, Leonardo A.;Kresse, Stine H.;Myklebost, Ola
平滑肌肉瘤是显示平滑肌分化的梭形细胞肿瘤。直到最近，大多数胃肠道间质瘤 (GIST) 还被归类为平滑肌肿瘤，但现在 GIST 被认为是一个单独的实体，定义为位于胃肠道的梭形细胞和/或上皮样肿瘤。使用基于微阵列的比较基因组杂交（阵列 CGH），我们创建了 7 个 GIST 和 12 个平滑肌肉瘤的 DNA 拷贝数变化的详细图谱。在两种肿瘤类型中都观察到染色体片段的大量增加和丢失。 GIST 中观察到的最常见畸变是 14 号和 22 号染色体丢失，14q11.2-q32.33（71% 的肿瘤）和 22q12.2-q13.31（100%）中的复发区域最少。在平滑肌肉瘤中，观察到 10 号和 13q 染色体频繁丢失，10q21.3 (7590) 和 13q14.2-q14.3 (75%) 的复发区域最少。在平滑肌肉瘤中检测到 17p13.1-p11.2 反复出现高水平扩增。使用 cDNA 微阵列进行的表达谱分析显示该区域有四个高表达的候选基因（AURKB、SREBF1、MFAP4 和 FLJ10847）。此前已在其他恶性肿瘤中观察到 AURKB 和 SREBF1 表达的改变。所有样本的分层聚类将胃肠道间质瘤和平滑肌肉瘤分成两个不同的簇。统计分析确定了 6 个染色体区域：1p36.11-p13.1、9q21.11-9q34.3、14q11.2-q23.2、14q31.3-q32.33、15q24.3-q26.3 和 22q11.21-q13.31，它们之间的拷贝数存在显着差异。胃肠道间质瘤和平滑肌肉瘤。我们的结果显示了使用阵列比较基因组杂交对组织学相似的肿瘤（例如胃肠道间质瘤和平滑肌肉瘤）进行分类的潜力。
Leiomyosarcomas are spindle cell tumors showing smooth muscle differentiation. Until recently, most gastrointestinal stromal tumors (GIST) were also classified as smooth muscle tumors, but now GISTs are recognized as a separate entity, defined as spindle cell and/or epithelioid tumors localized in the gastrointestinal tract. Using microarray-based comparative genomic hybridization (array CGH), we have created a detailed map of DNA copy number changes for 7 GISTs and 12 leiomyosarcomas. Considerable gains and losses of chromosomal segments were observed in both tumor types. The most frequent aberration observed in GISTs was loss of chromosomes 14 and 22, with minimal recurrent regions in 14q11.2-q32.33 (71% of the tumors) and 22q12.2-q13.31 (100%). In leiomyosarcomas, frequent loss of chromosome 10 and 13q was observed, with minimal recurrent regions in 10q21.3 (7590) and 13q14.2-q14.3 (75%). Recurrent high-level amplification of 17p13.1-p11.2 was detected in leiomyosarcomas. Expression profiling using cDNA microarrays revealed four candidate genes in this region with high expression (AURKB, SREBF1, MFAP4, and FLJ10847). Altered expression of AURKB and SREBF1 has been observed previously in other malignancies. Hierarchical clustering of all samples separated GISTs and leiomyosarcomas into two distinct clusters. Statistical analysis identified six chromosomal regions, 1p36.11-p13.1, 9q21.11-9q34.3, 14q11.2-q23.2, 14q31.3-q32.33, 15q24.3-q26.3, and 22q11.21-q13.31, which were significantly different in copy number between GISTs and leiomyosarcomas. Our results show the potential of using array comparative genomic hybridization to classify histologically similar tumors such as GISTs and leiomyosarcomas.