Integrated Analysis of DNA Methylation and Mutations in Esophageal Squamous cell Carcinoma.

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Title
Integrated Analysis of DNA Methylation and Mutations in Esophageal Squamous cell Carcinoma.
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Description

Abstract

The recent development of next-generation sequencing technology for extensive mutation analysis, and beadarray technology for genome-wide DNA methylation analysis has made it possible to obtain integrated pictures of genetic and epigenetic alterations, using the same cancer samples. In this study, we aimed to characterize such a picture in esophageal squamous cell carcinomas (ESCCs). Base substitutions of 55 cancer-related genes and copy number alterations (CNAs) of 28 cancer-related genes were analyzed by targeted sequencing. Forty-four of 57 ESCCs (77%) had 64 non-synonymous somatic mutations, and 24 ESCCs (42%) had 35 CNAs. A genome-wide DNA methylation analysis using an Infinium HumanMethylation450 BeadChip array showed that the CpG island methylator phenotype was unlikely to be present in ESCCs, a different situation from gastric and colon cancers. Regarding individual pathways affected in ESCCs, the WNT pathway was activated potentially by aberrant methylation of its negative regulators, such as SFRP1, SFRP2, SFRP4, SFRP5, SOX17, and WIF1 (33%). The p53 pathway was inactivated by TP53 mutations (70%), and potentially by aberrant methylation of its downstream genes. The cell cycle was deregulated by mutations of CDKN2A (9%), deletions of CDKN2A and RB1 (32%), and by aberrant methylation of CDKN2A and CHFR (9%). In conclusion, ESCCs had unique methylation profiles different from gastric and colon cancers. The genes involved in the WNT pathway were affected mainly by epigenetic alterations, and those involved in the p53 pathway and cell cycle regulation were affected mainly by genetic alterations.

KEYWORDS:

DNA methylation; cancer-related pathway; epigenetics; esophageal squamous cell carcinoma (ESCC); genetic alterations

(医博甲676)

Author
著者 岸野 貴督
著者(ヨミ) キシノ タカヨシ
著者(別表記) Kishino Takayoshi
Publication Title
Molecular Carcinogenesis
Publication Title Alternative
Mol Carcinog.
Volume
55
Issue
12
Start Page
2077
End Page
2088
Publisher
Wiley-Liss
Wiley
Published Date
2016-01-12
ISSN
0899-1987
NCID
AA10671664
PMID
26756304
DOI
10.1002/mc.22452
Resource Type
Thesis or Dissertation
Language
eng
Relation
出版社版DOIリンク(URL): https://doi.org/10.1002/mc.22452
Resource URL
https://doi.org/10.1002/mc.22452
Rights
© 2016 Wiley Periodicals, Inc.
Non-Commercial
DOI: https://doi.org/10.1002/mc.22452
Text Version
ETD
Grant ID
博甲第676号
Grant Date
2018-03-24
Degree Name
博士(医学)
Grantor
香川大学
Set
香川大学
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