Project description:Gastric cancer is one of the most aggressive cancers and is the second leading cause of cancer death worldwide. Approximately 40% of global gastric cancer cases occur in China, with peritoneal metastasis being the prevalent form of recurrence and metastasis in advanced disease (>50%). Currently, there are limited clinical approaches for predicting and treatment of peritoneal metastasis, resulting in a 6- month average survival time. By comprehensive genome analysis will uncover the pathogenesis of peritoneal metastasis. Here we describe a comprehensive whole-genome and transcriptome sequencing analysis of one advanced gastric cancer case, including non-cancerous mucosa, primary cancer and matched peritoneal metastatic cancer. The peripheral blood is used as normal control.
Project description:Gastric cancer is one of the leading causes of cancer mortality worldwide, and peritoneal metastasis is a hallmark of incurable advanced gastric cancer. The identification of molecular vulnerability for such conditions is imperative to improve the prognosis of gastric cancer. Here, we comprehensively analysed cancer cells purified from malignant ascitic fluid samples and their corresponding cell lines from 98 patients, through whole-genome sequencing, whole transcriptome sequencing, methylation analyses, and genome-wide enhancer analyses.
Project description:Gastric cancer is one of the leading causes of cancer mortality worldwide, and peritoneal metastasis is a hallmark of incurable advanced gastric cancer. The identification of molecular vulnerability for such conditions is imperative to improve the prognosis of gastric cancer. Here, we comprehensively analysed cancer cells purified from malignant ascitic fluid samples and their corresponding cell lines from 98 patients, through whole-genome sequencing, whole transcriptome sequencing, methylation analyses, and genome-wide enhancer analyses.
Project description:Gastric cancer is one of the leading causes of cancer mortality worldwide, and peritoneal metastasis is a hallmark of incurable advanced gastric cancer. The identification of molecular vulnerability for such conditions is imperative to improve the prognosis of gastric cancer. Here, we comprehensively analysed cancer cells purified from malignant ascitic fluid samples and their corresponding cell lines from 98 patients, through whole-genome sequencing, whole transcriptome sequencing, methylation analyses, and genome-wide enhancer analyses.
Project description:<p>BRCA1 mutations are a hallmark of hereditary ovarian cancer, strongly linked to deficiencies in homologous recombination (HR) DNA repair and impaired DNA replication fork protection. However, its roles in cancer progression beyond maintaining genomic integrity remain poorly understood. Through metabolomics approaches, we found BRCA1-deficiency strikingly increased choline metabolism. Loss of BRCA1 promotes choline uptake through upregulating choline transporter-like protein 4 (CTL4). BRCA1 directly binds and recruits EZH2-mediated H3K27Me3 deposition to CTL4 promoter. CTL4 was therefore overexpressed in ovarian cancer tissues with BRCA1 mutations. Furthermore, BRCA1-deficiency significantly promotes ovarian cancer invasion, while inhibition of CTL4 reverses the high metastatic potential of BRCA1-deficient ovarian cancer cells, suggesting the functionality and specificity of CTL4 as a therapeutic target. Additionally, we discovered that phosphocholine, the choline metabolite increased by CTL4 overexpression, interacted with and stabilized the epithelial-to-mesenchymal transition inducer FAM3C in BRCA1-deficient ovarian cancer cells. Importantly, we identified a potent CTL4 inhibitor, DT-13, which significantly reduces choline metabolism and effectively suppresses metastasis in BRCA1-deficient ovarian cancers. Therefore, our study uncovers a mechanism underlying metastasis in BRCA1-deficient cancers and identifies CTL4 as a therapeutic target for metastatic ovarian cancer patients with BRCA1 mutations.</p>