Gains and amplifications of c-myc, EGFR, and 20.q13 loci in the no dysplasia-dysplasia-adenocarcinoma sequence of Barrett's esophagus
Gains and amplifications of c-myc, EGFR, and 20.q13 loci in the no dysplasia-dysplasia-adenocarcinoma sequence of Barrett's esophagus
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DOI：
10.1158/1055-9965.epi-07-2734
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发表时间：
2008-06-01
影响因子：
3.8
通讯作者：
Krishnadath, Kausillia K.
中科院分区：
文献类型：
--
作者：
Rygiel, Agnieszka M.;Milano, Francesca;Krishnadath, Kausillia K.
Barrett食管向食管腺癌的进展通常以遗传异常的积累为特征。目的是评估几个癌基因位点的拷贝数改变，包括7 p12 [表皮生长因子受体（EGFR）]，8 q24（c-myc）和20 q13在Barrett食管的非异型增生-异型增生-腺癌序列中。应用荧光原位杂交技术检测了99例Barrett食管不同分期的异型增生或食管腺癌患者的刷片细胞学标本中7号染色体着丝粒区和7 p12（EGFR）、8 q24（c-myc）和20 q13位点特异性区域的DNA探针。非异型增生Barrett食管中17号染色体、8 q24（c-myc）和20 q13位点的增加（3-4个拷贝）频率较低。其频率随不典型增生的分期而增加，在食管腺癌中的发生率最高。在14%的高度异型增生中观察到至少1个基因座扩增（>4个拷贝），在食管腺癌中增加到50%（P = 0.015）。在高度异型增生/食管腺癌病例中，最常见的扩增位点是c-myc（18%），其次是20 q13（13%）和EGFR（11%）。与高度异型增生（20%; P = 0.049）相比，高扩增水平（>10个拷贝）的基因座在食管腺癌（72%）中更常见。c-myc、EGFR和20 q12基因座的扩增可作为Barrett食管高度异型增生或食管腺癌患者的诊断标志物。基因座的增益可能是有价值的预后标志物，因为它们已经存在于非异型增生的情况下，并可能之前的扩增后的事件中观察到的高度异型增生和食管腺癌。
The progression of Barrett's esophagus to esophageal adenocarcinoma is often characterized by the accumulation of genetic abnormalities. The goal was to evaluate the copy number alterations of several oncogene loci, including 7p12 [epidermal growth factor receptor (EGFR)], 8q24 (c-myc), and 20q13 in the sequence of no dysplasia-dysplasia-adenocarcinoma of Barrett's esophagus. Fluorescence in situ hybridization with DNA probes for the centromeric region of chromosome 7 and the locus-specific regions of 7p12 (EGFR), 8q24 (c-myc), and 20q13 was applied on 99 brush cytology specimens of patients with Barrett's esophagus with different stages of dysplasia or esophageal adenocarcinoma. Gains (3-4 copies) of chromosome 17, 8q24 (c-myc), and 20q.13 loci were found in the low frequencies in nondysplastic Barrett's esophagus. Their frequencies increased with the stage of dysplasia and reached a high incidence in esophageal adenocarcinoma. Amplification (>4 copies) of at least 1 of the loci was observed in 14% of high-grade dysplasia and increased to 50% in esophageal adenocarcinoma (P = 0.015). The most frequently amplified locus was c-myc (18%), followed by 20q13 (13%) and EGFR (11%) in the high-grade dysplasia/esophageal adenocarcinoma cases. High amplification levels (>10 copies) of the loci were more frequent in esophageal adenocarcinoma (72%) compared with high-grade dysplasia (20%; P = 0.049). Amplifications of the c-myc, EGFR, and 20q12 loci may serve as diagnostic markers to identify patients with Barrett's esophagus with high-grade dysplasia or esophageal adenocarcinoma. Gains of the loci might be of value as prognostic markers because they are already present in nondysplasia cases and may precede the later event of the amplification as observed in high-grade dysplasia and esophageal adenocarcinoma.