Genomic characterization of esophageal squamous cellcarcinoma:insights from next-generation sequencing

Two major types of cancer occur in the esophagus: squamous cell carcinoma, which is associated with chronic smoking and alcohol consumption, and adenocarcinoma, which typically arises in gastric reflux-associated Barrett's esophagus. Although there is increasing incidence of esophageal adenocarcinoma in Western counties, esophageal squamous cell carcinoma(ESCC) accounts for most esophageal malignancies in East Asia, including China and Japan. Technological advances allowing for massively parallel, high-throughput next-generation sequencing(NGS) of DNA have enabled comprehensive characterization of somatic mutations in large numbers of tumor samples. Recently, several studies were published in which whole exome or whole genome sequencing was performed in ESCC tumors and compared with matched normal DNA. Mutations were validated in several genes, including in TP53, CDKN2 A, FAT1, NOTCH1, PIK3 CA, KMT2 D and NFE2L2, which had been previously implicated in ESCC. Several new recurrent alterations have also been identified in ESCC. Combining the clinicopathological characteristics of patients with information obtained from NGS studies may lead to the development of effective diagnostic and therapeutic approaches for ESCC. As this research becomes more prominent, it is important that gastroenterologist become familiar with the various NGS technologies and the results generated using these methods. In the present study, we describe recent research approaches using NGS in ESCC.

Down-regulated expression of NPM1 in IMS-M2 cell line by(-)-epigallocatechin-3-gallate

Objective:To investigate the inhibited effect of epigallocatechin-3-gallate(EGCG)on the expression of NPM1 in IMS-M2 cells harboring the NPMl mutations.Methods:Cell proliferation assay was performed to test the effects of EGCG on eell growth of IMS-M2 cells harboring the NPM1 mutations.Western blot analysis were performed to test the protein expression of NPM1,AKT,those associated with apoplosis.Results:EGCG can down-regulate the expression of NPM1 in IMS-M2 cells harboring the NPM1mutations.Moreover,EGCG also suppressed the cell proliferation and induced apoptosis in IMSM2 cells.Conclusions:The results suggested that EGCG could be considered as a reagent for treatment of AML patients with NPM1 mutations.

Hunt for the tipping point during endocrine resistance process in breast cancer by dynamic network biomarkers

Acquired drug resistance is the major reason why patients fail to respond to cancer therapies.It is a challenging task to deter.mine the tipping point of endocrine resistance and detect the associated molecules.Derived from new systems biology theory, the dynamic network biomarker (DNB) method is designed to quantitatively identify the tipping point of a drastic system transition and can theoretically identify DNB genes that play key roles in acquiring drug resistance.We analyzed time-course mRNA sequence data generated from the tamoxifen-treated estrogen receptor (ER)-positive MCF-7 cell line, and identified the tipping point of endocrine resistance with its leading molecules.The results show that there is interplay between gene mutations and DNB genes, in which the accumulated mutations eventually affect the DNB genes that subsequently cause the change of transcriptional landscape, enabling full-blown drug resistance. Survival analyses based on clinical datasets validated that the DNB genes were associated with the poor survival of breast cancer patients.The results provided the detection for the pre-resistance state or early signs of endocrine resistance.Our predictive method may greatly benefit the scheduling of treatments for complex diseases in which patients are exposed to considerably different drugs and may become drug resistant.