Open AccessIntegrative genome‐wide analyses reveal the transcriptional aberrations in Japanese esophageal squamous cell carcinoma
Author(s) -
Takemoto Akira,
Tanimoto Kousuke,
Mori Seiichi,
Inoue Jun,
Fujiwara Naoto,
Noda Tetsuo,
Inazawa Johji
Publication year - 2021
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.15063
Subject(s) - biology , epigenomics , dna methylation , gene , genetics , exome sequencing , transcriptome , cpg site , methylation , gene expression , mutation
Esophageal squamous cell carcinoma (ESCC) is a malignant disease. At present, the genomic profiles of ESCC are known to a considerable extent, and DNA methylation and gene expression profiles have been mainly used for the classification of ESCC subtypes, but integrative genomic, transcriptomic, and epigenomic analyses remain insufficient. Therefore, we performed integrative analyses using whole‐exome sequencing, DNA methylation, and RNA sequencing (RNA‐seq) analyses of Japanese patients with ESCC. In cancer‐related genes, such as NOTCH family genes, RTK/PI3K pathway genes, and NFE2L2 pathway genes, variants and copy number amplification were detected frequently. Japanese ESCC cases were clustered into two mutational signatures: an APOBEC‐associated signature and an age‐related signature. In imprinted genes, DNA methylation was aberrant in gene promoter regions and correlated well with gene expression profiles. Nonsynonymous single‐nucleotide variants and allelic expression imbalance were detected frequently in FAT family genes. Our integrative genome‐wide analyses, including DNA methylation and allele‐specific gene expression profiles, revealed altered gene regulation of imprinted genes and FAT family genes in ESCC.