Array Comparative Genomic Hybridization of Enchondroma and Grade 1 Chondrosarcoma

背景与目的：内生性软骨瘤与低级别软骨肉瘤的组织学相似，难以进行病理诊断。阵列比较基因组杂交（CGH）是检测基因拷贝数的各种增益和损失的有用工具，为研究特定疾病的发生提供了重要信息。我们进行了阵列CGH来确定内生性软骨瘤和1级软骨肉瘤之间基因组改变的差异。方法：采用阵列CGH技术对9例软骨瘤（EC）和8例1级软骨肉瘤（CS）冷冻标本的拷贝数变化进行分析。我们分析了内生性软骨瘤和1级软骨肉瘤的基因组改变及其相关的遗传变化，并重点研究了每种组织学类型中超过一半的病例（EC: 25/9例，CS: 24/8例）中检测到的特定拷贝数变化。结果：所有样本均存在遗传失衡。两组间拷贝数变化较大。阵列CGH显示特定的基因失衡，在内生纤维瘤中有20个增益和14个损失，在1级软骨肉瘤中有41个增益和16个损失。基因拷贝获得最多的区域为2q12.1-2（60%）、6p22（60%）、7q11.2（53%）、15q13.2（53%）、21q22.1（60%）和22q13.3(60%)，基因拷贝缺失最多的区域为1q21.3（87%）、6p21.3（73%）、7q22.1（60%）、19q13.2（67%）、20q11.2（93%）和20q13.1-2（80%）。软骨肉瘤中检测到的特异性区域为11p15.4、12q13.2、17q12和13q14。在78%的内生纤维瘤中观察到WDR5的增加。在所有I级软骨肉瘤中均观察到CHK2的增加，75%的患者观察到DTX3的增加。这些基因可能是与I级软骨肉瘤进展相关的候选基因。结论：我们使用阵列CGH在内生纤维瘤和1级软骨肉瘤中发现了一些特定的基因组改变，尽管这两种肿瘤之间存在更多相似的基因组改变。在本研究中，array-CGH检测到I级CS中CHK2、RARA和DTX3的增加，内生性瘤中WDR5的增加。CHK2和WDR5基因可能是I级CS和EC中肿瘤进展的靶点。少

Background and Aims: It is difficult to make pathological diagnosis between enchondroma and low grade chondrosacoma because of similar histology. Array comparative genomic hybridization (CGH), which is a useful tool to detect various gains and losses of gene copy number, provides important information about the genesis of specific diseases. We performed array CGH to identify the difference of genomic alterations between enchondroma and grade 1 chondrosarcoma.Methods: We performed array CGH to assess the copy number changes in frozen specimens of 9 enchondroma (EC) and 8 grade 1 chondrosarcoma (CS),those were collected surgically and diagnosed histologically. We analyzed genomic alterations of enchondroma and grade 1 chondrosarcoma and those related genetic changes, and focused on the specific copy number change detected in more than half cases of each histological type (EC:〓25/9 cases, CS:〓24/8cases).Results: Genetic imbalances were found in all samples. There were similar copy number … More changes between two groups. Array CGH showed specific genetic imbalances of20 gains and 14 losses in enchondroma, and 41 gains and 16 losses in grade 1 chondrosarcoma. The most common regions of gain of gene copy in both samples were 2q12.1-2(60%),6p22(60%),7q11.2(53%),15q13.2( 53%),21q22.1(60%)and 22q13.3(60%),and the most common regions of loss were 1q21.3(87%),6p21.3( 73%),7q22.1(60%), 19q13.2(67%),20q11.2( 93%),and 20q13.1-2(80%). The specific regions detected in enchondroma were 9q34 and 13q12, and those detected in those chondrosarcoma,11p15.4,12q13.2,17q12, and 13q14. Gain of WDR5 was observed in seventy-eight percent of enchondroma. Gain of CHK2 was observed in all grade I chondrosarcoma, and gain of DTX3 was observed in seventy-five percent. These genes may be candidate genes related to the progression of grade I chondrosarcoma.Conclusion: We demonstrated several specific genomic alternations detected in enchondroma and grade 1 chondrosarcoma using array CGH, although there were more similar genomic alterations between both tumors. In this study, array-CGH identified gain of CHK2, RARA, and DTX3 in grade I CS, and gain of WDR5 in enchondroma. CHK2 and WDR5 gene may be a target of tumor progression in grade I CS and EC. Less