Prediction of CCND1 amplification using plasma DNA as a prognostic marker in oesophageal squamous cell carcinoma

Takeshita, Hitoshi; Ichikawa, Daisuke; Komatsu, Shuhei; Tsujiura, Masahiro; Kosuga, Toshiyuki; Deguchi, Katsuya; Konishi, Hirotaka; Morimura, Ryo; Shiozaki, Atsushi; Fujiwara, Hitoshi; Okamoto, Kazuma; Otsuji, Eigo

doi:10.1038/sj.bjc.6605657

Cited by 18 publications

(7 citation statements)

References 20 publications

(19 reference statements)

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“…It ranks eighth in order of occurrence worldwide and sixth as the leading cause of death (4,5). china has the highest Ec incidence and mortality rates in the world (1,2,5).…”

Section: Introductionmentioning

confidence: 99%

Hypermethylation-modulated down-regulation of CDH1 expression contributes to the progression of esophageal cancer

Ling

Li²,

Ge³

et al. 2011

Int J Mol Med

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Abstract. CDH1, a cell adhesion molecule, which plays a key role in maintaining the epithelial phenotype, is regarded as an invasion-suppressor gene in light of accumulating evidence from in vitro experiments and clinical observations. In an attempt to clarify the mechanism responsible for inactivation of this gene in carcinomas, we investigated the methylation status of the CDH1 gene 5'-cpG islands and its regulatory mechanism in the progression of esophageal squamous cell carcinoma. Real-time methylation-specific polymerase chain reaction (qMSP) and treatment with the demethylating agent 5-aza-2'-deoxycytidine (5-Aza-cdR) were conducted to analyze the methylation status at the CDH1 promoter region in the human esophageal carcinoma cell lines, Ec1 and Ec9706. A total of 235 invasive esophageal squamous cell carcinomas (EScc) at stages I-IV and their corresponding normal tissue samples, were included in an immunohistochemistry study and methylation analysis of CDH1. The results demonstrate that in Ec1 and Ec9706 cells, the CDH1 promoter is methylated and treatment with 5-Aza-cdR restored CDH1 expression. Enhanced CDH1 expression decreased cell migration, invasion ability and increased adhesion ability. decreased CDH1 expression was detected in 59.6% of EScc tissues, compared with their adjacent non-neoplastic epithelia, which had a close correlation with the primary tumor status, lymph node status, distant metatasis and clinicopathologic stage. Hypermethylation at the CDH1 promoter was detected in 97.9% of 140 cases of EScc with low CDH1 expression. The methylation of CDH1 promoters (P=0.929) was closely correlated with the lack of expression of their corresponding proteins. The cox regression model for survival analysis showed that increases in CDH1 methylation had a greater impact on the prognosis than tumor clinical stage. These findings suggest that CDH1 gene silencing by promoter hypermethylation and the resultant reduction of CDH1 expression may play an important role in the progression of EScc. CDH1 methylation was a significant predictor of survival in EScc patients after surgery.

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“…It ranks eighth in order of occurrence worldwide and sixth as the leading cause of death (4,5). china has the highest Ec incidence and mortality rates in the world (1,2,5).…”

Section: Introductionmentioning

confidence: 99%

Hypermethylation-modulated down-regulation of CDH1 expression contributes to the progression of esophageal cancer

Ling

Li²,

Ge³

et al. 2011

Int J Mol Med

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“…The CCND1 gene is recurrently mutated in ESCC with amplifications reported in 33-46% of patients [62][63][64]. The level of CCND1 in plasma was significantly higher in patients with ESCC than healthy controls [65], also when only patients with superficial ESCC were investigated [66]. Furthermore, the survival was significantly poorer in patients with high CCDN1 levels than in patients with low level.…”

Section: Copy Number Variants In Candidate Genesmentioning

confidence: 99%

“…It has been suggested that ctDNA analysis could also be used for detection of minimal residual disease after surgery [85]. This hypothesis has not been tested in GEC, but a number of studies have confirmed that mutant allele frequencies in ctDNA drop after resection of the tumor for GC [59,72,86] as well as ESCC [57,58,65,66].…”

Section: Monitoring Of Treatment Response and Resistancementioning

confidence: 99%

Tumor-specific genetic aberrations in cell-free DNA of gastroesophageal cancer patients

et al. 2018

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“…ctDNA analysis of patients with squamous cell carcinoma (SCC) of the esophagus with the use of a 90gene panel was associated with sensitivity of 94% and 75%, respectively, when detecting ≥1 or ≥2 mutant genes, suggesting that ctDNA analysis can help monitor treatment effect in these patients [32]. In multivariate analysis, a higher plasma cyclin D1 (CCND1; 11q13) to dopamine receptor D2 (DRD2; 11q22-23) ratio (C/D ratio) was significantly correlated with worse prognosis [33]. In another study, high concordance of multiple somatic mutations was found between plasma ctDNA and tumor (primary or metastases) DNA (83%-100%).…”

Section: Esophageal Carcinomamentioning

confidence: 99%

Circulating tumor DNA analysis in the era of precision oncology

et al. 2020

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The spatial and temporal genomic heterogeneity of various tumor types and advances in technology have stimulated the development of circulating tumor DNA (ctDNA) genotyping. ctDNA was developed as a non-invasive, cost-effective alternative to tumor biopsy when such biopsy is associated with significant risk, when tumor tissue is insufficient or inaccessible, and/or when repeated assessment of tumor molecular abnormalities is needed to optimize treatment. The role of ctDNA is now well established in the clinical decision in certain alterations and tumors, such as the epidermal growth factor receptor (EGFR) mutation in non-small cell lung cancer and the v-Ki-ras2 kirsten rat sarcoma viral oncogene homolog (KRAS) mutation in colorectal cancer. The role of ctDNA analysis in other tumor types remains to be validated. Evolving data indicate the association of ctDNA level with tumor burden, and the usefulness of ctDNA analysis in assessing minimal residual disease, in understanding mechanisms of resistance to treatment, and in dynamically guiding therapy. ctDNA analysis is increasingly used to select therapy. Carefully designed clinical trials that use ctDNA analysis will increase the rate of patients who receive targeted therapy, will elucidate our understanding of evolution of tumor biology and will accelerate drug development and implementation of precision medicine. In this article we provide a critical overview of clinical trials and evolving data of ctDNA analysis in specific tumors and across tumor types.

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Prediction of CCND1 amplification using plasma DNA as a prognostic marker in oesophageal squamous cell carcinoma

Cited by 18 publications

References 20 publications

Hypermethylation-modulated down-regulation of CDH1 expression contributes to the progression of esophageal cancer

Hypermethylation-modulated down-regulation of CDH1 expression contributes to the progression of esophageal cancer

Tumor-specific genetic aberrations in cell-free DNA of gastroesophageal cancer patients

Circulating tumor DNA analysis in the era of precision oncology

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