Genomic imbalances pinpoint potential oncogenes and tumor suppressors in Wilms tumors.
Genomic imbalances pinpoint potential oncogenes and tumor suppressors in Wilms tumors.
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DOI：
10.1186/s13039-016-0227-y
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发表时间：
2016
影响因子：
1.3
通讯作者：
Carraro DM
中科院分区：
文献类型：
--
作者：
Krepischi ACV;Maschietto M;Ferreira EN;Silva AG;Costa SS;da Cunha IW;Barros BDF;Grundy PE;Rosenberg C;Carraro DM
肾母细胞瘤（WT）的发病机制尚未完全阐明。DNA拷贝数改变（CNAs）在癌症中很常见，并且经常定义关键的致病事件。这项工作的目的是研究CNAs，以揭示Wilms肿瘤发生的新候选基因。未进行化疗的50例原发性WTs的阵列- cgh显示了一些以前未报道的复发性CNAs，如7q和20q的增加，以及7p的损失。基因组扩增仅在3例后来复发的WTs中检测到，这也显示出影响16.2 Mb 1q21.1-q23.2区域的增益频率增加，11p， 11q远端和16q的损失，以及WT1缺失。相反，13和19号染色体的非整倍体仅在WTs中发现，没有进一步复发。与WT复发相关的1q21.1-q23.2增益包含CHD1L、CRABP2、GJA8、MEX3A和MLLT11等基因，这些基因在WT中被发现过表达。此外，局灶缺失所包含的基因的下调突出了新的潜在肿瘤抑制因子，如CNKSR1， MAN1C1, PAQR7 (1p36), TWIST1, SOSTDC1 (7p14.1-p12.2)， BBOX和FIBIN （11p13）以及PLCG2 （16q）。本研究证实了以前与WT相关的CNAs的存在，并描述了仅在少数病例中发现的新CNAs。后者在复发病例中出现的频率更高，这表明它们可能与WT进展有关。本文的在线版本（doi:10.1186/s13039-016-0227-y）包含补充材料，仅供授权用户使用。
Wilms tumor (WT) has a not completely elucidated pathogenesis. DNA copy number alterations (CNAs) are common in cancer, and often define key pathogenic events. The aim of this work was to investigate CNAs in order to disclose new candidate genes for Wilms tumorigenesis. Array-CGH of 50 primary WTs without pre-chemotherapy revealed a few recurrent CNAs not previously reported, such as 7q and 20q gains, and 7p loss. Genomic amplifications were exclusively detected in 3 cases of WTs that later relapsed, which also exhibited an increased frequency of gains affecting a 16.2 Mb 1q21.1-q23.2 region, losses at 11p, 11q distal, and 16q, and WT1 deletions. Conversely, aneuploidies of chromosomes 13 and 19 were found only in WTs without further relapse. The 1q21.1-q23.2 gain associated with WT relapse harbours genes such as CHD1L, CRABP2, GJA8, MEX3A and MLLT11 that were found to be over-expressed in WTs. In addition, down-regulation of genes encompassed by focal deletions highlighted new potential tumor suppressors such as CNKSR1, MAN1C1, PAQR7 (1p36), TWIST1, SOSTDC1 (7p14.1-p12.2), BBOX and FIBIN (11p13), and PLCG2 (16q). This study confirmed the presence of CNAs previously related to WT and characterized new CNAs found only in few cases. The later were found in higher frequency in relapsed cases, suggesting that they could be associated with WT progression. The online version of this article (doi:10.1186/s13039-016-0227-y) contains supplementary material, which is available to authorized users.