title: Molecular alterations in colorectal adenomas and intramucosal adenocarcinomas defined by high-density single-nucleotide polymorphism arrays.
abstract: BACKGROUND
  We examined colorectal adenomas and intramucosal adenocarcinomas (IMAs) to develop a genome-wide overview of copy number alterations (CNAs) during colorectal tumorigenesis.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Genomic alterations play an essential role in early colorectal carcinogenesis. CNAs in colorectal tumours provide new insights for evaluation of colorectal tumorigenesis.
authors.affiliation: Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, 19-1, Uchimaru, Morioka, 020-8505, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Eizuka
authors.affiliation: Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, 19-1, Uchimaru, Morioka, 020-8505, Japan. tsugai@iwate-med.ac.jp.
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Sugai
authors.affiliation: Department of Pharmacodynamics and Molecular Genetics, School of Pharmacy, Iwate Medical University, Morioka, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Habano
authors.affiliation: Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, 19-1, Uchimaru, Morioka, 020-8505, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Uesugi
authors.affiliation: Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, 19-1, Uchimaru, Morioka, 020-8505, Japan.
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kawasaki
authors.affiliation: Department of Molecular Biology, School of Medicine, Sapporo Medical University, Sapporo, Japan.
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Yamamoto
authors.affiliation: Department of Molecular Biology, School of Medicine, Sapporo Medical University, Sapporo, Japan.
authors.forename: Hiromu
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsumoto
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D000236:Adenoma / Q000235:genetics / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D015894:Genome, Human; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D020641:Polymorphism, Single Nucleotide
keywords: Colorectal adenoma; Copy number alteration; Gain; Intramucosal adenocarcinoma; Loss of heterozygosity