Genome-wide analysis of Ollier disease: Is it all in the genes?
Genome-wide analysis of Ollier disease: Is it all in the genes?
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DOI：
10.1186/1750-1172-6-2
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发表时间：
2011-01-14
影响因子：
3.7
通讯作者：
Bovée JV
中科院分区：
文献类型：
--
作者：
Pansuriya TC;Oosting J;Krenács T;Taminiau AH;Verdegaal SH;Sangiorgi L;Sciot R;Hogendoorn PC;Szuhai K;Bovée JV
Ollier病是一种罕见的非遗传性疾病，其特征在于存在多发性内生软骨瘤（EC），这是一种发生在骨髓内的良性软骨肿瘤，具有不对称分布。向中央软骨肉瘤（CS）恶性转化的风险增加高达35%。奥利耶病的病因不明。我们对28名Ollier患者的37个肿瘤进行了全基因组拷贝数和杂合性丢失（洛）分析，并结合使用Illumina BeadArray v3.0对6名患者的7个EC进行了表达阵列。在FAM86D、PRKG 1和ANKS 1B处发现非复发性EC特异性拷贝数改变。在两个无关的Ollier患者的两个EC中发现6号染色体拷贝数丢失的洛。其中1例患者在3号染色体上也有洛缺失。然而，没有共同的基因组改变被发现的所有EC。使用SNP和表达阵列的整合方法，我们鉴定了POU5F1的丢失以及下调和NIPBL的获得以及上调。这些候选区域在两名以上的Ollier患者中均未受到影响，表明这些变化是EC发展中的随机次要事件。OllierCS中的遗传变异和洛缺失的数目增加，主要发生在染色体9p、6q、5q和3p上。我们提出了第一个全基因组分析的最大的国际系列的奥利耶EC和CS报告迄今为止，并证明拷贝数的改变和洛是罕见的，而继发性CS是遗传不稳定的奥利耶EC的非复发性。人们可以预测，相反，小缺失，点突变或表观遗传机制在奥利耶病的EC起源中发挥作用。
Ollier disease is a rare, non-hereditary disorder which is characterized by the presence of multiple enchondromas (ECs), benign cartilaginous neoplasms arising within the medulla of the bone, with an asymmetric distribution. The risk of malignant transformation towards central chondrosarcoma (CS) is increased up to 35%. The aetiology of Ollier disease is unknown. We undertook genome-wide copy number and loss of heterozygosity (LOH) analysis using Affymetrix SNP 6.0 array on 37 tumours of 28 Ollier patients in combination with expression array using Illumina BeadArray v3.0 for 7 ECs of 6 patients. Non-recurrent EC specific copy number alterations were found at FAM86D, PRKG1 and ANKS1B. LOH with copy number loss of chromosome 6 was found in two ECs from two unrelated Ollier patients. One of these patients also had LOH at chromosome 3. However, no common genomic alterations were found for all ECs. Using an integration approach of SNP and expression array we identified loss as well as down regulation of POU5F1 and gain as well as up regulation of NIPBL. None of these candidate regions were affected in more than two Ollier patients suggesting these changes to be random secondary events in EC development. An increased number of genetic alterations and LOH were found in Ollier CS which mainly involves chromosomes 9p, 6q, 5q and 3p. We present the first genome-wide analysis of the largest international series of Ollier ECs and CS reported so far and demonstrate that copy number alterations and LOH are rare and non-recurrent in Ollier ECs while secondary CS are genetically unstable. One could predict that instead small deletions, point mutations or epigenetic mechanisms play a role in the origin of ECs of Ollier disease.
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影响因子：
64.8
作者：
通讯作者：
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影响因子：
12.3
作者：
Lin S;Carvalho B;Cutler DJ;Arking DE;Chakravarti A;Irizarry RA
通讯作者：
Irizarry RA
影响因子：
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作者：
Knijnenburg, J.;Oberstein, S. A. J. Lesnik;Szuhai, K.
通讯作者：
Szuhai, K.
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3.3
作者：
Bovée, JVMG;van Roggen, JFG;Hogendoorn, PCW
通讯作者：
Hogendoorn, PCW
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作者：
Fu, XY;McGrath, S;Kamps, MP
通讯作者：
Kamps, MP