Genomic changes in primary lesion and lymph node metastases of esophageal squamous cell carcinoma

Abstract

BACKGROUND & OBJECTIVE: Local lymph node and blood metastasis could occur at early stage of esophageal squamous cell carcinoma (ESCC), which may be the key factors of its recurrence and poor prognosis. However, the mechanism of ESCC metastasis is unclear. This study was to analyze the genetic changes in primary lesion and lymph node metastases of ESCC, to screen for and locate ESCC metastasis-related genes. METHODS: Genomic alterations in 15 pairs of primary lesions and matched metastatic lymph nodes of ESCC were analyzed by comparative genomic hybridization (CGH). RESULTS: In the 15 pairs of tissues, the most common chromosomal alterations were the gains of 3q, 8q, 6p, 20p, 5p, 18p, 2p, 2q and 1q, and the losses of 10p, 10q, 17p, 18q, 4p and 13q. Of these changes, the most significant finding was the gain of 6p with a frequency of 47% in metastatic lymph nodes and 13% in primary lesions, and the gain of 20p with a frequency of 73% in metastatic lymph nodes and 33% in primary lesions. The second interesting finding was the loss of 10p with a frequency of 53% in metastatic lymph nodes and 13% in primary lesions, and the loss of 10q with a frequency of 47% in metastatic lymph nodes and 13% in primary lesions. CONCLUSION: The gains of 6p and 20p and the losses of 10p and 10q are common genomic alterations in primary lesion and lymph node metastases of ESCC, which may code ESCC metastasis-related genes.

背景與目的:食管癌早期可發生局部淋巴或血行轉移,這是導致復發和預后差的主要原因。但是,食管癌轉移發生的分子機制尚不清楚。本研究旨在分析食管癌原發灶和淋巴結轉移灶腫瘤細胞染色體變化的特征,尋找或定位與食管癌轉移相關基因,加深對其轉移機制的了解。方法:應用比較基因組雜交技術(comparativegenomichybridization,CGH)分析15例食管癌患者原發灶和其對應的淋巴結轉移灶的染色體基因組改變。結果:最常見染色體DNA拷貝數增加的部位是3q,8q,6p,20p,5p,18p,2p,2q,1q;常見的染色體DNA拷貝數丟失的部位是10p,10q,17p,18q,4p,13q。其中,最有意義的發現是6p增加(原發灶:2/15,13%,轉移灶:7/15,47%),20p增加(原發灶:5/15,33.3%,轉移灶:11/15,73.3%)。第二個發現是10p丟失(原發灶:2/15,13.3%,轉移灶:8/15,53%),10q丟失(原發灶:2/15,13.3%,轉移灶:7/15,46.6%)。結論:食管癌原發灶和淋巴結轉移灶細胞染色體基因組改變最顯著的部位是6p,20p的增加和10p,10q的丟失;這些部位可能存在與食管癌細胞淋巴結轉移相關的基因。