Abstract

BackgroundWe examined colorectal adenomas and intramucosal adenocarcinomas (IMAs) to develop a genome-wide overview of copy number alterations (CNAs) during colorectal tumorigenesis.MethodsWe 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.ResultsAlthough 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.ConclusionsGenomic alterations play an essential role in early colorectal carcinogenesis. CNAs in colorectal tumours provide new insights for evaluation of colorectal tumorigenesis.

Highlights

  • There have been advances in medical treatment of colorectal cancer (CRC) recently, CRC remains a major cause of cancer death in both men and women worldwideJ Gastroenterol (2017) 52:1158–1168[1]

  • Background We examined colorectal adenomas and intramucosal adenocarcinomas (IMAs) to develop a genome-wide overview of copy number alterations (CNAs) during colorectal tumorigenesis

  • 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

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Summary

Introduction

There have been advances in medical treatment of colorectal cancer (CRC) recently, CRC remains a major cause of cancer death in both men and women worldwideJ Gastroenterol (2017) 52:1158–1168[1]. Intramucosal cancer is an intermediate lesion between colorectal adenoma and invasive submucosal cancer, which is associated with a high risk of metastasis [2]. Colorectal adenoma and intramucosal cancer (adenocarcinoma) are important lesions for our understanding of early colorectal carcinogenesis [3]. Copy number alterations (CNAs) have been extensively investigated in CRC [12,13,14,15,16,17], the role of CNAs is not fully understood in the initial stages of colorectal carcinogenesis, colorectal adenoma and intramucosal adenocarcinoma [16, 17]. We examined colorectal adenomas and intramucosal adenocarcinomas (IMAs) to develop a genome-wide overview of copy number alterations (CNAs) during colorectal tumorigenesis

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