High-resolution 400K oligonucleotide array comparative genomic hybridization analysis of neurofibromatosis type 1-associated cutaneous neurofibromas
High-resolution 400K oligonucleotide array comparative genomic hybridization analysis of neurofibromatosis type 1-associated cutaneous neurofibromas
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DOI：
10.1016/j.gene.2014.12.064
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发表时间：
2015-03-10
期刊：
影响因子：
3.5
通讯作者：
Hosokawa, Yoshitaka
中科院分区：
文献类型：
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作者：
Asai, Akiko;Karnan, Sivasundaram;Hosokawa, Yoshitaka
1型神经纤维瘤病（NF1）是一种遗传性疾病，受影响的个体发展为良性或恶性神经系统肿瘤。迄今为止，NF1是由位于染色体带17q112的NF1肿瘤抑制基因突变引起的。在这项研究中，我们的目的是表征新的复发性区域染色体不平衡和肿瘤相关的候选基因在NF 1相关的皮肤神经纤维瘤。采用高分辨率400K寡核苷酸阵列比较基因组杂交（aCGH）对9例NF 1患者的皮肤神经纤维瘤进行了复发性染色体失衡筛查。所有病例均表现出至少一种亚显微镜异常。在至少三分之一的病例中，复发性染色体不平衡的区域是1q13的丢失。（33%，FAM19A3），1q21.1（44%，RABGAP 1L），2q37.1（56%，INPP5D），3p25.1（67%，CHCHD4），4p15.32（56%，FGFBP 1），5q11.2（56%，ARL15），6q22.31（56%，NKAIN 2），6q22.33（67%，ARHGAP 18），6q25.1（67%，UST），2013年第7季度（56%，ADCY1），12q13.13（44%，KRT 71）、19q13.32（56%，GRLF 1）和20p11.21（56%，NLP），以及2p23.3（76%，C2orf53）、8q22.3（44%，ODF 1）和8q24.3（67%，ARC）的增益。几种染色体不平衡，包括7q1123，13q14.1，14q32.13，17p12和17q11.2的丢失，检测频率较低。我们还证实，这些染色体不平衡没有检测到患者匹配的淋巴细胞DNA。在复发性染色体不平衡区域鉴定的6个肿瘤相关候选基因（RABGAP1L、ADCY1、SLIT2、GRLF1、UST和ARC）中，发现UST（下调）和ARC（上调）的基因表达变化与拷贝数改变显著相关。新的复发性染色体不平衡和肿瘤相关候选基因表达水平的改变可能与NF1相关良性皮肤神经纤维瘤的发生有关。(C)© 2014 Elsevier B.V.保留所有权利。
Neurofibromatosis type 1 (NF1) is a genetic disorder where affected individuals develop benign or malignant nervous system tumors. To date, NF1 is caused by mutations in the NF1 tumor suppressor gene located at chromosome band 17q112. In this study, we aimed to characterize novel recurrent regional chromosomal imbalances and tumor-related candidate genes in NF1-associated cutaneous neurofibromas. Nine cutaneous neurofibromas from NF1 patients were screened for recurrent chromosomal imbalances using high-resolution 400K oligonudeotide array comparative genomic hybridization (aCGH). All the cases exhibited at least one sub-microscopic abnormality. Regions of recurrent chromosomal imbalances in a least one third of cases were loss of 1q13.2 (33%, FAM19A3), 1q21.1 (44%, RABGAP1L), 2q37.1 (56%, INPP5D), 3p25.1 (67%, CHCHD4), 4p15.32 (56%, FGFBP1), 5q11.2 (56%, ARL15), 6q22.31 (56%, NKAIN2), 6q22.33 (67%, ARHGAP18), 6q25.1 (67%, UST), 7q13 (56%, ADCY1), 12q13.13 (44%, KRT71),19q13.32 (56%, GRLF1), and 20p11.21 (56%, NLP) and gain of 2p23.3 (76%, C2orf53), 8q22.3 (44%, ODF1) and 8q24.3 (67%, ARC). Several chromosomal imbalances, including loss of 7q1123, 13q14.1, 14q32.13, 17p12, and 17q11.2 were detected at a lower frequency. We also confirmed that these chromosomal imbalances were not detected in the patient-matched lymphocyte DNAs. Amongst the 6 tumor-related candidate genes (RABGAP1L,ADCY1, SLIT2, GRLF1, UST, and ARC) identified in the regions of recurrent chromosomal imbalances, the gene expression changes of UST (down-regulation) and ARC (up-regulation) were found to be significantly associated with copy number alterations. The novel recurrent chromosomal imbalances and the altered expression levels of the tumor-related candidate genes may be associated with the development of NF1-associated benign cutaneous neurofibromas. (C) 2014 Elsevier B.V. All rights reserved.