Project description:Circulating tumor DNA (ctDNA) as a biomarker of disease activity in classic Hodgkin lymphoma (cHL) patients are still not well-defined. By profiling primary tumors and ctDNA, we identified common variants between primary tumors and longitudinal plasma samples in most of the cases, confirming high PBatial and temporal heterogeneity. Though ctDNA analyses mirrored HRS cell genetics overall, the prevalence of variants shows that none of them can be used as a single biomarker. Conversely, the estimation of hGE/mL, based in total ctDNA quantification, reflects disease activity and is almost perfectly correlated with standard parameters such as PET/CT that are associated with refractoriness.
Project description:Early gastric cancers (EGC) precede advanced gastric cancers (AGC) with a favorable clinical outcome compared to advanced gastric cancers (AGC). To understand the progression mechanisms of EGC to AGC, it is required to disclose the EGC and AGC genomes in terms of the the mutational and evolutionary perspectives. In this study, we performed whole-exome sequencing and copy number profiling of nine microsatellite (MS)-unstable (MSI-H) (5 EGC and 4 AGC) and eight MS-stable (MSS) gastric cancers (4 EGC and 4 AGC). Unexpectedly, we observed no substantial differences in the number, sequence composition and functional consequences (potential driver mutations and affected pathways) of the mutations and CNAs between EGC and AGC genomes in both MSI-H and MSS cases.
Project description:Background: Immunotherapy has increased the expected survival of patients with advanced HCC. However, objective radiological response to these therapies has been reported to occur in around 20% of patients. Our aim was to identify potential serological markers of response to ICIs. Methods: 25 patients with advanced HCC treated with immunotherapy were prospectively in-cluded. Cytokine and cfDNA/ctDNA levels were measured prior to first treatment administration (basal) and after 3 months of treatment. Basal ctDNA profiling was also analyzed. Results: Basal levels of CTLA-4, cfDNA and ctDNA were significantly different in patients presenting progres-sive disease as best radiological response. The percentage of patients with basal mutations in CDKN2A was significantly higher in patients presenting progressive disease and they have a significantly lower number of CNV. Levels at 3 months of starting the treatment of MCP-1, TNF-alpha, cfDNA and ctDNA were also significantly different between patients with and without progressive disease. Higher cfDNA and ctDNA levels were associated with a poorer overall survival. Conclusion: Analysis of cfDNA and cytokines could help to stratify patients according to expected response to immunotherapies.
Project description:This study aims to compared ctDNA methylation status induced by ionizing to different ograns. SD rats were irradiated with local radaition to brain, lung or skin. Serum was collected and subjiected to ctDNA extraction. ctDNA were then treated by methylation-sensive bisulfite and sequencing.
Project description:Early gastric cancers (EGC) precede advanced gastric cancers (AGC) with a favorable clinical outcome compared to advanced gastric cancers (AGC). To understand the progression mechanisms of EGC to AGC, it is required to disclose the EGC and AGC genomes in terms of the the mutational and evolutionary perspectives. In this study, we performed whole-exome sequencing and copy number profiling of nine microsatellite (MS)-unstable (MSI-H) (5 EGC and 4 AGC) and eight MS-stable (MSS) gastric cancers (4 EGC and 4 AGC). Unexpectedly, we observed no substantial differences in the number, sequence composition and functional consequences (potential driver mutations and affected pathways) of the mutations and CNAs between EGC and AGC genomes in both MSI-H and MSS cases. Gastrectomy tissues from 17 GC patients were used for this study. The hospital pathology department confirmed pathologic features of the GC (e.g., EGC vs. AGC, differentiation, lymph node metastasis and TNM stage). All of the picked areas from tumor and normal areas were frozen, cut, and stained with hematoxylin & eosin (H&E). Two pathologists selected cases with rich tumor cell population (at least 60%), which were subsequently used in the study. Copy number profiling was performed using Agilent 180K platform according to the manufacturer's protocol.
Project description:Medulloblastoma (MB) is an embryonal tumor of the cerebellum and a highly malignant childhood brain tumor. Cell-free circulating tumor DNA (ctDNA) from the cerebrospinal fluid (CSF) of patients with brain tumors faithfully represent genomic alterations of brain tumors. Distinct epigenetic signatures among subgroups of MB allow us to detect epigenetic alterations in CSF to aid classify and guide therapy of MB tumors. Here, we evaluate DNA methylation and hydroxymethylation of ctDNA derived from small amount of CSF (200 µL) and matched tumor DNA from 3 MB patients. We find highly concordance of DNA methylation and hydroxymethylation between CSF ctDNA and tumor DNA, especially in CpG islands. Importantly, CSF ctDNA can mostly recapitulate the dynamic changes of DNA methylation and hydroxymehtylation in tumor species compared to healthy cerebellums. Those MB tumor signature CpGs’ DNA methylation status are recovered in CSF ctDNA can clearly distinguish MB subgroups by utilizing public large cohort data. We further identified potential diagnostic and prognostic DNA methylation markers in CSF ctDNA. Our results show that CSF ctNDA methylation and hydroxymethylation can be a minimal invasive method to assess epigenetic alterations of MB, which is complementary to current diagnoses of MB tumors.
Project description:Long non-coding RNAs (lncRNAs) may contribute to tumorigenesis and cancer progression by regulating the gene in various cancers, including advanced gastric cancer (AGC). To investigate differentially expressed lncRNAs in AGC, we use whole transcriptome sequencing in 3 pairs of human gastric adenocarcinoma and the corresponding normal tissues.
Project description:Patients with advanced gastric cancers (AGCs) would experience poor prognosis, lacking investigation on comprehensive ecosystem profile and specific prognostic factors. Here, we conducted patient stratification based on unsupervised clustering of transcriptomic profile of 108 normal/tumor AGC pairs and integrated single-cell RNA transcriptome profile of 116 gastric cancer/normal samples, revealing the heterogeneity of AGC, which can be stratified into distinct AGC-related signature (AGCRS)-based patient groups with different prognosis. AGCRS scores are over-presented in cancer-associated fibroblasts (CAF) and increase in metastasis-enriched subtypes (e.g., myofibroblastic CAF). More prolific cell-cell communications were observed between CAF and metastasis-enriched epithelial/endothelial through collagen-related interactions. Experimentally, CAF conditional-medium can enhance the tube formation of endothelial cells and HOXC-AS2-related migration ability of gastric cancer cells. Particularly, HOX-AS2 can facilitate the nucleus translocation of YBX1 through direct binding in cytoplasm and induce the epithelial-mesenchymal transition. Our findings highlight the potential prognostic role of AGC heterogeneity induced by CAF-related communications.