Flat-type colorectal advanced adenomas (laterally spreading tumors) have different genetic and epigenetic alterations from protruded-type advanced adenomas View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2006-11-24

AUTHORS

Taiga Takahashi, Katsuhiko Nosho, Hiroyuki Yamamoto, Masashi Mikami, Hiroaki Taniguchi, Nobuki Miyamoto, Yasushi Adachi, Fumio Itoh, Kohzoh Imai, Yasuhisa Shinomura

ABSTRACT

Morphologically, colorectal adenomas can be divided into two groups, protruded-type and flat-type. However, the accurate frequencies of genetic and epigenetic alterations in flat-type colorectal advanced adenomas (laterally spreading tumors) have remained largely unknown. In the current study, we investigated genetic and epigenetic alterations in 101 flat-type colorectal advanced adenomas and 68 protruded-type colorectal advanced adenomas by using direct DNA sequencing and quantitative real-time PCR (MethyLight), respectively. KRAS mutation was detected in a significantly higher percentage of flat-type adenomas (35%) than in protruded-type adenomas (13%). When the samples were limited to the tumors in the distal colon, the difference of KRAS mutation was still significant. KRAS mutation in G-to-A transitions at codons 12 and 13 was detected in a significantly higher percentage of flat-type adenomas (26%) than in protruded-type adenomas (9%). BRAF and β-catenin mutations were detected in 3 and 8% of the 101 flat-type adenomas, respectively. No significant difference was found between frequencies of those mutations in flat-type adenomas and protruded-type adenomas. Methylations of MGMT, CDKN2A (p16) and MLH1 were detected in 28, 33 and 9% of the 101 flat-type adenomas, respectively. CDKN2A methylation was detected in a significantly lower percentage of flat-type adenomas than in protruded-type adenomas (63%). Methylation of at least one gene was detected in a significantly lower percentage of flat-type adenomas (54%) than in protruded-type adenomas (78%). In conclusion, KRAS mutation was frequently detected in flat-type advanced adenomas and the mutational patterns in most of them with KRAS mutations were a transition from G-to-A. Therefore, these genetic alterations seem to play an important role in the development of flat-type advanced adenomas, especially in the distal colon. Epigenetic alterations infrequently occurred in flat-type advanced adenomas, suggesting that they have different genetic and epigenetic alterations from those of protruded-type advanced adenomas. More... »

PAGES

139-147

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/modpathol.3800722

DOI

http://dx.doi.org/10.1038/modpathol.3800722

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1041286606

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/17143260


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38 schema:description Morphologically, colorectal adenomas can be divided into two groups, protruded-type and flat-type. However, the accurate frequencies of genetic and epigenetic alterations in flat-type colorectal advanced adenomas (laterally spreading tumors) have remained largely unknown. In the current study, we investigated genetic and epigenetic alterations in 101 flat-type colorectal advanced adenomas and 68 protruded-type colorectal advanced adenomas by using direct DNA sequencing and quantitative real-time PCR (MethyLight), respectively. KRAS mutation was detected in a significantly higher percentage of flat-type adenomas (35%) than in protruded-type adenomas (13%). When the samples were limited to the tumors in the distal colon, the difference of KRAS mutation was still significant. KRAS mutation in G-to-A transitions at codons 12 and 13 was detected in a significantly higher percentage of flat-type adenomas (26%) than in protruded-type adenomas (9%). BRAF and β-catenin mutations were detected in 3 and 8% of the 101 flat-type adenomas, respectively. No significant difference was found between frequencies of those mutations in flat-type adenomas and protruded-type adenomas. Methylations of MGMT, CDKN2A (p16) and MLH1 were detected in 28, 33 and 9% of the 101 flat-type adenomas, respectively. CDKN2A methylation was detected in a significantly lower percentage of flat-type adenomas than in protruded-type adenomas (63%). Methylation of at least one gene was detected in a significantly lower percentage of flat-type adenomas (54%) than in protruded-type adenomas (78%). In conclusion, KRAS mutation was frequently detected in flat-type advanced adenomas and the mutational patterns in most of them with KRAS mutations were a transition from G-to-A. Therefore, these genetic alterations seem to play an important role in the development of flat-type advanced adenomas, especially in the distal colon. Epigenetic alterations infrequently occurred in flat-type advanced adenomas, suggesting that they have different genetic and epigenetic alterations from those of protruded-type advanced adenomas.
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52 PCR
53 accurate frequency
54 adenomas
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56 alterations
57 codon 12
58 colon
59 colorectal adenomas
60 colorectal advanced adenomas
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63 development
64 differences
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66 distal colon
67 epigenetic alterations
68 frequency
69 genes
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71 group
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77 mutational patterns
78 mutations
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