Home LiteratureArticle Details
PMID: 15016754 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Methylation patterns define two types of hyperplastic polyp associated with colorectal cancer.

Gut ·Vol. 53 ·No. 4 ·2004-04-00 ·Pages 573-80

Wynter CV, Walsh MD, Higuchi T, Leggett BA, Young J, Jass JR

Abstract

Hyperplastic polyps (HP) of the colorectum have traditionally been regarded as non-neoplastic lesions. Recent data implicate HP in the pathogenesis of colorectal cancers (CRC) characterised by extensive DNA methylation and microsatellite instability. The aim of this study was to identify morphological and molecular features that may characterise subtypes of HP with potential for neoplastic progression. HP (22) clustering around distal CRC (group I) were compared with HP (58) in subjects with hyperplastic polyposis (group II). DNA methylation was tested in methylated in tumour (MINT) loci (1, 2, 12, 31) and genes HPP1, MGMT, p14ARF, p16INK4a, and hMLH1. Group II HP showed significantly more methylation than group I HP at all loci except MINT1 and MGMT. Group I showed the lowest frequency of DNA methylation but the highest frequency of K-ras mutation. Group II HP (termed HP variant) had the morphological features of the recently described "sessile serrated adenomas". Methylation of hMLH1 was found most frequently in group II polyps that included foci of dysplasia (7/10) and in no group I lesions. The findings support the existence of morphological and molecular heterogeneity among HP and highlight a subset that is likely to have significant malignant potential.

MeSH Terms
Aged Colon/pathology Colonic Polyps/genetics,pathology Colorectal Neoplasms/genetics DNA Methylation DNA, Neoplasm/genetics Disease Progression Female Genes, ras Humans Hyperplasia/genetics,pathology Male Microsatellite Repeats Middle Aged Mutation Precancerous Conditions/genetics,pathology
Chemicals
DNA, Neoplasm
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Wynter C V A
Conjoint Gastroenterology Laboratory, Royal Brisbane and Women's Hospital Research Foundation, Bancroft Centre, Queensland, Australia. [email protected]
Walsh M D
Higuchi T
Leggett B A
Young J
Jass J R
References (43)
43 references, click to expand
  1. HPP1: a transmembrane protein-encoding gene commonly methylated in colorectal polyps and cancers.
    Proc Natl Acad Sci U S A. 2001 Jan 2;98(1):265-70 PMID: 11120884
  2. Hyperplastic polyps and DNA microsatellite unstable cancers of the colorectum.
    Histopathology. 2000 Oct;37(4):295-301 PMID: 11012735
  3. Methylation of O-6-methylguanine DNA methyltransferase characterizes a subset of colorectal cancer with low-level DNA microsatellite instability.
    Cancer Res. 2001 Feb 1;61(3):827-30 PMID: 11221863
  4. Inverse relationship between microsatellite instability and K-ras and p53 gene alterations in colon cancer.
    Am J Pathol. 2001 Apr;158(4):1517-24 PMID: 11290569
  5. Sporadic colorectal cancers with microsatellite instability and their possible origin in hyperplastic polyps and serrated adenomas.
    J Natl Cancer Inst. 2001 Sep 5;93(17):1307-13 PMID: 11535705
  6. Concordant CpG island methylation in hyperplastic polyposis.
    Am J Pathol. 2002 Feb;160(2):529-36 PMID: 11839573
  7. CpG island methylation in sporadic colorectal cancers and its relationship to microsatellite instability.
    Gastroenterology. 2002 May;122(5):1376-87 PMID: 11984524
  8. CpG island methylation in aberrant crypt foci of the colorectum.
    Am J Pathol. 2002 May;160(5):1823-30 PMID: 12000733
  9. Molecular characteristics of serrated adenomas of the colorectum.
    Gut. 2002 Aug;51(2):200-6 PMID: 12117880
  10. Morphological and molecular heterogeneity within nonmicrosatellite instability-high colorectal cancer.
    Cancer Res. 2002 Nov 1;62(21):6011-4 PMID: 12414620
  11. Morphologic reappraisal of serrated colorectal polyps.
    Am J Surg Pathol. 2003 Jan;27(1):65-81 PMID: 12502929
  12. Frequent CpG island methylation in serrated adenomas of the colorectum.
    Am J Pathol. 2003 Mar;162(3):815-22 PMID: 12598316
  13. Characterization of sporadic colon cancer by patterns of genomic instability.
    Cancer Res. 2003 Apr 1;63(7):1608-14 PMID: 12670912
  14. Hyperplastic-like colon polyps that preceded microsatellite-unstable adenocarcinomas.
    Am J Clin Pathol. 2003 Jun;119(6):778-96 PMID: 12817424
  15. BRAF and KRAS mutations in colorectal hyperplastic polyps and serrated adenomas.
    Cancer Res. 2003 Aug 15;63(16):4878-81 PMID: 12941809
  16. Genetics supersedes epigenetics in colon cancer phenotype.
    Cancer Cell. 2003 Aug;4(2):121-31 PMID: 12957287
  17. BRAF mutations in colon cancer are not likely attributable to defective DNA mismatch repair.
    Cancer Res. 2003 Sep 1;63(17):5209-12 PMID: 14500346
  18. Structure and significance of metaplastic nodules in the rectal mucosa.
    J Clin Pathol. 1968 Nov;21(6):735-43 PMID: 5717544
  19. Rapid detection of ras oncogenes in human tumors: applications to colon, esophageal, and gastric cancer.
    Oncogene. 1989 Jul;4(7):923-8 PMID: 2666911
  20. Mixed hyperplastic adenomatous polyps/serrated adenomas. A distinct form of colorectal neoplasia.
    Am J Surg Pathol. 1990 Jun;14(6):524-37 PMID: 2186644
  21. Identification and quantification of aberrant crypt foci and microadenomas in the human colon.
    Hum Pathol. 1991 Mar;22(3):287-94 PMID: 1706308
  22. Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis.
    Nature. 1993 Jun 10;363(6429):558-61 PMID: 8505985
  23. Molecular determinants of dysplasia in colorectal lesions.
    Cancer Res. 1994 Nov 1;54(21):5523-6 PMID: 7923189
  24. Methylation of the oestrogen receptor CpG island links ageing and neoplasia in human colon.
    Nat Genet. 1994 Aug;7(4):536-40 PMID: 7951326
  25. Serrated adenomatous polyposis in humans.
    Gastroenterology. 1996 Mar;110(3):748-55 PMID: 8608884
  26. Familial giant hyperplastic polyposis predisposing to colorectal cancer: a new hereditary bowel cancer syndrome.
    J Pathol. 1996 May;179(1):20-5 PMID: 8691339
  27. Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands.
    Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9821-6 PMID: 8790415
  28. Methylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair-defective human tumor cell lines.
    Cancer Res. 1997 Mar 1;57(5):808-11 PMID: 9041175
  29. High frequency of K-ras mutations in human colorectal hyperplastic polyps.
    Gut. 1997 May;40(5):660-3 PMID: 9203947
  30. Alternative genetic pathways in colorectal carcinogenesis.
    Proc Natl Acad Sci U S A. 1997 Oct 28;94(22):12122-7 PMID: 9342373
  31. Infrequent K-ras codon 12 mutation in serrated adenomas of human colorectum.
    Gut. 1998 May;42(5):680-4 PMID: 9659164
  32. The human ARF cell cycle regulatory gene promoter is a CpG island which can be silenced by DNA methylation and down-regulated by wild-type p53.
    Mol Cell Biol. 1998 Nov;18(11):6457-73 PMID: 9774662
  33. DNA microsatellite instability in hyperplastic polyps, serrated adenomas, and mixed polyps: a mild mutator pathway for colorectal cancer?
    J Clin Pathol. 1999 Jan;52(1):5-9 PMID: 10343605
  34. CpG island methylator phenotype in colorectal cancer.
    Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8681-6 PMID: 10411935
  35. Optimisation of DNA and RNA extraction from archival formalin-fixed tissue.
    Nucleic Acids Res. 1999 Aug 15;27(16):e12 PMID: 10454649
  36. Distinct methylation pattern and microsatellite instability in sporadic gastric cancer.
    Int J Cancer. 1999 Oct 29;83(3):309-13 PMID: 10495421
  37. Characterisation of a subtype of colorectal cancer combining features of the suppressor and mild mutator pathways.
    J Clin Pathol. 1999 Jun;52(6):455-60 PMID: 10562815
  38. Distinct genetic profiles in colorectal tumors with or without the CpG island methylator phenotype.
    Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):710-5 PMID: 10639144
  39. Hypermethylation-associated inactivation of p14(ARF) is independent of p16(INK4a) methylation and p53 mutational status.
    Cancer Res. 2000 Jan 1;60(1):129-33 PMID: 10646864
  40. Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is associated with G to A mutations in K-ras in colorectal tumorigenesis.
    Cancer Res. 2000 May 1;60(9):2368-71 PMID: 10811111
  41. Neoplastic progression occurs through mutator pathways in hyperplastic polyposis of the colorectum.
    Gut. 2000 Jul;47(1):43-9 PMID: 10861263
  42. Phenotypic and molecular characteristics of hyperplastic polyposis.
    Gastroenterology. 2000 Aug;119(2):323-32 PMID: 10930367
  43. Hyperplastic polyposis: association with colorectal cancer.
    Am J Surg Pathol. 2001 Feb;25(2):177-84 PMID: 11176066
Article Info
Journal
Gut
Abbr.
Gut
ISSN
0017-5749
DOI
10.1136/gut.2003.030841
Email
[email protected]
Published
2004-04-00
Pages
573-80
Language
English
Region
England
NLM ID
2985108R
PMCID
PMC1774017
Subset
IM
Grants
NCI NIH HHS · R01 CA077057 · United States
NCI NIH HHS · CA77057 · United States
External Links
PubMed source DOI: 10.1136/gut.2003.030841 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2