Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, 19-1, Uchimaru, Morioka, 020-8505, Japan.
Department of Pharmacodynamics and Molecular Genetics, School of Pharmacy, Iwate Medical University, Morioka, Japan.
J Gastroenterol. 2017 Nov;52(11):1158-1168. doi: 10.1007/s00535-017-1317-2. Epub 2017 Feb 14.
We examined colorectal adenomas and intramucosal adenocarcinomas (IMAs) to develop a genome-wide overview of copy number alterations (CNAs) during colorectal tumorigenesis.
We analysed CNAs using a high-resolution SNP array of isolated tumour glands obtained from 55 colorectal adenomas (35 low-grade adenomas and 20 high-grade adenomas) and 30 IMAs. Next, we examined whether frequent CNAs differed between low-grade and high-grade adenomas or high-grade adenomas and IMAs. Finally, we investigated the total lengths of the CNAs in low-grade adenomas, high-grade adenomas, and IMAs.
Although no frequent CNAs were found in low-grade adenomas, the most frequent alterations of high-grade adenomas were gains of 7q11, 7q21 and 9p13 and loss of 5q14.3-35. High levels of gains were detected at 13q, 7q, 8p, 20q, 7p, 18p and 17p in IMAs. Although no frequent alteration differed between low-grade and high-grade adenomas, significant differences of gains at 13q, 17p and 18p were found between high-grade adenoma and IMAs. Although the total lengths of all CNAs (gains and losses), copy number gains, and losses of heterozygosity were significantly greater in high-grade adenomas than in low-grade adenomas, no significant differences in the lengths of CNAs were found between high-grade adenomas and IMAs.
Genomic alterations play an essential role in early colorectal carcinogenesis. CNAs in colorectal tumours provide new insights for evaluation of colorectal tumorigenesis.
我们研究了结直肠腺瘤和黏膜内腺癌（IMAs），以全面了解结直肠肿瘤发生过程中的拷贝数改变（CNAs）。
我们使用从 55 个结直肠腺瘤（35 个低级别腺瘤和 20 个高级别腺瘤）和 30 个 IMA 中分离出的肿瘤腺体的高分辨率 SNP 阵列分析 CNAs。接下来，我们检查低级别和高级别腺瘤之间或高级别腺瘤和 IMA 之间是否存在频繁的 CNA 差异。最后，我们研究了低级别腺瘤、高级别腺瘤和 IMA 中的 CNA 总长度。
尽管在低级别腺瘤中未发现频繁的 CNA，但高级别腺瘤最常见的改变是 7q11、7q21 和 9p13 的增益和 5q14.3-35 的丢失。在 IMA 中检测到 13q、7q、8p、20q、7p、18p 和 17p 的高水平增益。尽管低级别和高级别腺瘤之间没有频繁改变，但在高级别腺瘤和 IMA 之间发现了 13q、17p 和 18p 增益的显著差异。尽管所有 CNA（增益和丢失）、拷贝数增益和杂合性丢失的总长度在高级别腺瘤中明显大于低级别腺瘤，但在高级别腺瘤和 IMA 之间没有发现 CNA 长度的显著差异。
基因组改变在结直肠早期癌变中起重要作用。结直肠肿瘤中的 CNA 为评估结直肠肿瘤发生提供了新的见解。
