Molecular alterations in colorectal adenomas and intramucosal adenocarcinomas defined by high-density single-nucleotide polymorphism arrays

Makoto Eizuka,Tamotsu Sugai,Takayuki Matsumoto,Hiromu Suzuki,Keisuke Kawasaki,Eiichiro Yamamoto,Yayoi Takahashi,Wataru Habano,Noriyuki Uesugi

doi:10.1007/s00535-017-1317-2

Makoto Eizuka, Tamotsu Sugai + Show 7 more

Open Access

https://doi.org/10.1007/s00535-017-1317-2

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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

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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