Genome-wide catalogue of chromosomal aberrations in barrett's esophagus and esophageal adenocarcinoma: a high-density single nucleotide polymorphism array analysis.
Genome-wide catalogue of chromosomal aberrations in barrett's esophagus and esophageal adenocarcinoma: a high-density single nucleotide polymorphism array analysis.
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Barrett食管和食管腺癌中染色体畸变的全基因组分类：高密度的单核苷酸多态性阵列分析。
DOI：
10.1158/1940-6207.capr-09-0265
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发表时间：
2010-09
期刊：
影响因子：
--
通讯作者：
Wu X
中科院分区：
文献类型：
--
作者：
Gu J;Ajani JA;Hawk ET;Ye Y;Lee JH;Bhutani MS;Hofstetter WL;Swisher SG;Wang KK;Wu X
为了更好地了解食管腺癌(EAC)肿瘤发生的分子机制，我们使用高密度单核苷酸多态性(SNP)阵列分析了101例患者在四个顺序进展阶段-Barrett化生(BM)、低度不典型增生(LGD)、高度不典型增生(HGD)和EAC的染色体异常。我们观察到一个明显的趋势，即进展期较高的染色体丢失增加。BM、LGD、HGD和EAC的平均缺失臂数分别为0.30、3.21、7.70和11.90条(趋势P值分别为4.82×10−7)，等位基因缺失的SNPs平均百分比分别为0.1%、1.8%、6.6%和17.2%(趋势P值分别为2.64×10−6)。在LGD中，3p14.2(68.4%)和16q23.1(47.4%)的丢失仅限于FHIT(3p14.2)和WWOX(16q23.1)基因的狭窄区域，而9p21(68.4%)的丢失发生在较大的区域。HGD和EAC的其他染色体区域丢失显著增加，17P丢失是EAC中最常见的事件之一。包括FHIT、WWOX、RUNX1、KIF26B、MGC48628、PDE4D、C20orf133、GMDS、DMD和PARK2在内的许多反复出现的小区域染色体丢失干扰了单基因，其中大部分是人类基因组中常见的脆性位点(CFS)区域。而位于21q22的RUNX1基因可能是EAC的潜在抑癌基因。扩增的频率低于丢失，主要发生在EAC。8q24(含Myc)和8p23.1(含CTSB)是扩增频率最高的两个区域。此外，增加扩增的显著趋势与较高的进展阶段相关。
To better understand the molecular mechanisms behind esophageal adenocarcinoma (EAC) tumorigenesis, we used high-density single nucleotide polymorphism (SNP) arrays to profile chromosomal aberrations at each of the four sequential progression stages – Barrett’s metaplasia (BM), low-grade dysplasia (LGD), high-grade dysplasia (HGD), and EAC, in 101 patients. We observed a significant trend toward increasing loss of chromosomes with higher progression stage. For BM, LGD, HGD, and EAC, respectively, the average numbers of chromosome arms with loss per sample were 0.30, 3.21, 7.70, and 11.90 (P for trend= 4.82 × 10−7), and the mean percentages of SNPs with allele loss were 0.1%, 1.8%, 6.6%, and 17.2% (P for trend = 2.64 × 10−6). In LGD, loss of 3p14.2 (68.4%) and 16q23.1 (47.4%) was limited to narrow regions within the FHIT (3p14.2) and WWOX (16q23.1) genes, whereas loss of 9p21 (68.4%) occurred in larger regions. A significant increase in the loss of other chromosomal regions was seen in HGD and EAC; loss of 17p (47.6%) was one of the most frequent events in EAC. Many recurrent small regions of chromosomal loss disrupted single genes, including FHIT, WWOX, RUNX1, KIF26B, MGC48628, PDE4D, C20orf133, GMDS, DMD, and PARK2, most of which are common fragile site (CFS) regions in the human genome. But RUNX1 at 21q22 appeared to be a potential tumor suppressor gene in EAC. Amplifications were less frequent than losses and mostly occurred in EAC. The 8q24 (containing Myc) and 8p23.1 (containing CTSB) were the two most frequently amplified regions. In addition, a significant trend toward increasing amplification was associated with higher progression stage.