Single Nucleotide Polymorphism Array Profiling Identifies Distinct Chromosomal Aberration Patterns Across Colorectal Adenomas and Carcinomas
Single Nucleotide Polymorphism Array Profiling Identifies Distinct Chromosomal Aberration Patterns Across Colorectal Adenomas and Carcinomas
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DOI：
10.1002/gcc.22243
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发表时间：
2015-05-01
影响因子：
3.7
通讯作者：
Wong，Jason W. H.
中科院分区：
文献类型：
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作者：
Zarzour，Peter;Boelen，Lies;Wong，Jason W. H.
良性结直肠腺瘤向癌症的发展与染色体畸变的积累有关。尽管染色体畸变的模式和频率在结直肠癌中已经得到了很好的确定，但在腺瘤中相应的畸变模式却没有得到很好的记录。本研究的目的是分析结直肠腺瘤和癌的染色体畸变，以便更好地了解肿瘤发生和发展过程中的关键变化。对216对结直肠肿瘤/正常配对进行单核苷酸多态性阵列分析，其中60对为腺瘤，156对为癌。虽然许多染色体畸变是癌症特有的，但在癌症中频率最高的染色体畸变（染色体7、13q和20q的扩增；17p和18号染色体的缺失；1p、染色体4、5q、8p、17p、染色体18和20p的缺失）也在腺瘤中发现。利用染色体畸变的分层聚类揭示了三种不同的亚型。有趣的是，这些亚型仅部分依赖于肿瘤分期。一组染色体频繁缺失的结直肠癌患者预后最差，该组患者中也存在大量腺瘤（n= 9），这表明，至少在某些肿瘤中，染色体畸变模式在肿瘤形成的早期阶段就已确定。最后，对LOH事件的分析显示，拷贝中性/获得性LOH （CN/G - LOH）在5q、11q、15q、17p、18、20p和22q染色体上很常见（约10%）。腺瘤中有时会出现相应区域的缺失，这表明这些位点的LOH可能在肿瘤发生中起重要作用。©2015 Wiley期刊公司
The progression of benign colorectal adenomas into cancer is associated with the accumulation of chromosomal aberrations. Even though patterns and frequencies of chromosomal aberrations have been well established in colorectal carcinomas, corresponding patterns of aberrations in adenomas are less well documented. The aim of this study was to profile chromosomal aberrations across colorectal adenomas and carcinomas to provide a better insight into key changes during tumor initiation and progression. Single nucleotide polymorphism array analysis was performed on 216 colorectal tumor/normal matched pairs, comprising 60 adenomas and 156 carcinomas. While many chromosomal aberrations were specific to carcinomas, those with the highest frequency in carcinomas (amplification of chromosome 7, 13q, and 20q; deletion of 17p and chromosome 18; LOH of 1p, chromosome 4, 5q, 8p, 17p, chromosome 18, and 20p) were also identified in adenomas. Hierarchical clustering using chromosomal aberrations revealed three distinct subtypes. Interestingly, these subtypes were only partially dependent on tumor staging. A cluster of colorectal cancer patients with frequent chromosomal deletions had the least favorable prognosis, and a number of adenomas (n= 9) were also present in the cluster suggesting that, at least in some tumors, the chromosomal aberration pattern is determined at a very early stage of tumor formation. Finally, analysis of LOH events revealed that copy‐neutral/gain LOH (CN/G‐LOH) is frequent (>10%) in carcinomas at 5q, 11q, 15q, 17p, chromosome 18, 20p, and 22q. Deletion of the corresponding region is sometimes present in adenomas, suggesting that LOH at these loci may play an important role in tumor initiation. © 2015 Wiley Periodicals, Inc.