Abstract
Almost all cancer cells possess multiple epigenetic abnormalities, which cooperate with genetic alterations to enable the acquisition of cancer hallmarks during tumorigenesis. As the most frequently found epigenetic change in human cancers, aberrant DNA methylation manifests at two major forms: global genomic DNA hypomethylation and locus-specific promoter region hypermethylation. It has been recognized as a critical contributor to esophageal squamous cell carcinoma (ESCC) malignant transformation. In ESCC, DNA methylation alterations affect genes involved in cell cycle regulation, DNA damage repair, and cancer-related signaling pathways. Aberrant DNA methylation patterns occur not only in ESCC tumors but also in precursor lesions. It adds another layer of complexity to the ESCC heterogeneity and may serve as early diagnostic, prognostic, and chemo-sensitive markers. Characterization of the DNA methylome in ESCC could help better understand its pathogenesis and develop improved therapies. We herein summarize the current research and knowledge about DNA methylation in ESCC and its clinical significance in diagnosis, prognosis, and treatment.
Highlights
As the ninth most common cancer in the world, esophageal carcinoma is the sixth leading cause of cancer-related deaths [1]
DNA methylation heterogeneity has been quantified and been linked to clinical variables in various cancer types, including prostate cancer [16], chronic lymphocytic leukemia [17], glioblastoma [18], Ewing sarcoma [19], as well as esophageal squamous cell carcinoma (ESCC) [20]. These findings demonstrate the power of DNA methylation sequencing in analyzing intratumor heterogeneity
We summarize recent advances regarding DNA methylation changes in the initiation and progression of ESCC
Summary
As the ninth most common cancer in the world, esophageal carcinoma is the sixth leading cause of cancer-related deaths [1]. Esophageal squamous cell carcinoma (ESCC) is the predominant subtype of esophageal carcinoma and accounts for ∼90% of the cases [2]. Enormous progress has been made in early diagnosis and multimodal therapies, the prognosis of ESCC patients remains dismal, with the overall 5-year survival rate below 30% [2, 3]. Intensive molecular biological studies have revealed that epigenetic dysregulation is a fundamental characteristic of most human cancers [4]. The most widely studied epigenetic modification is DNA methylation, which is the most frequently found abnormal epigenetic change in human cancers. DNA methylation occurs predominantly at the 5′ position of cytosine forming cytosine guanine dinucleotides.
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