Clinical sequencing of 1134 colorectal cancer tumors.
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina HiSeq 2000, Illumina HiSeq 2500
ORGANISM(S): Homo Sapiens
SUBMITTER: MSKCC
PROVIDER: PRJEB23844 | EVA | 2017-12-09
REPOSITORIES: EVA
Similar Datasets
Project description:We have performed bulk RNA sequencing on colorectal tumors in order to determine their transcriptome-based molecular subtypes. RNA was isolated from fresh frozen human colorectal tumor specimens with Trizol extraction. RNA library preparation was performed with KAPA stranded mRNA sequencing kit, during which mRNA selection was performed with polyT capture beads. Sequencing was performed on Illumina HiSeq4000 as single-end 51 bp reads. File names include dataset name (KUL3), patient code(SCXXX), sample region (core or border) and sample code (EXTXXX): DATASETNAME_PATIENTCODE_SAMPLEREGION_rSAMPLE_CODE_...fastq.gz
2020-04-05 | E-MTAB-8412 | biostudies-arrayexpress
Project description:Primary prostate tumor samples sequenced with MSK-IMACT, a hybridization capture-based next-generation sequencing assay. Custom DNA probes were designed for targeted sequencing of all exons and selected introns of 468 genes.
2019-08-12 | PRJEB33969 | EVA
Project description:Single Gland Whole-exome sequencing: building on our prior description of multi-region WES of colorectal tumors and targeted single gland sequencing (E-MTAB-2247), we performed WES of multiple single glands from different sides (right: A and left: B) of two tumors in this study (tumor O and U) on the illumina platform using the Agilent SureSelect 2.0 or illumina Nextera Rapid Capture Exome kit (SureSelect or NRCE, as indicated in the naming of fastq files). Colorectal Cancer Xenograft Whole-exome sequencing: The HCT116 and LoVo Mismatch-Repair-deficient colorectal adenocarcinoma cell lines were obtained from the ATCC and cultured under standard conditions. For both cell lines, a single âfoundingâ cell was cloned and expanded in vitro to ~6M cells. Two aliquots of ~1M cells were subcutaneously injected into opposite flanks (right and left) of a nude mouse and tumors allowed to reach a size of ~1B cells (1cm3) before the animal was sacrificed. Tumor tissue was collected separately from the right and left lesions and DNA was extracted for WES using the illumina TruSeq Exome kit or Nextera Rapid Capture Exome expanded Kits (Truseq or NRCEe), as was DNA from the first passage population (a polyclonal tissue culture for HCT116 and a polyclonal xenograft sample for LoVo), which were employed as a control to study mutation accumulation in culture and post xenotransplantation.
2017-05-01 | E-MTAB-5547 | biostudies-arrayexpress
Project description:Evaluation of cell free circulating DNA (cfDNA) has recently been proposed for tracking disease relapse in colorectal cancer (CRC). Such assays could overcome the issues of classical monitoring, but requires personalized assay design due to absence of common alteration. On the contrary, early methylation alterations are restricted to delimited genomic loci allowing comprehensive assay design for population study. Our objective was to identify new cancer specific methylation biomarkers fitted to assess cfDNA over treatment, thus monitoring response in the metastatic CRC (mCRC) setup. Genome wide methylation profiling of colorectal cancer cell lines (surrogate to pure tumor tissue) was carried out and compared to publically available normal healthy colon mucosa (cancer unrelated). Identified loci were validated in additional publically available cohorts. Digital PCR assays were designed for selected markers and assessed in cfDNA of self-declared healthy donors (>40 years old), and of mCRC patients. Longitudinal assessment was performed in a subset of colorectal cancer patients treated with different therapy regimen (chemotherapy or targeted agents). Samples from the current GEOset were extracted by Wizard SV Genomic DNA Purification System (Promega). DNA samples were checked for integrity by 1% agarose gel, and quantity via Picogreen quantification. All samples were bisulfite converted using the EZ DNA methylation Gold kit (Zymo Research) with a minimum input of 500ng and following manufacturer’s instructions. Infinium HumanMethylation450 BeadChip arrays were carried out according to the Illumina Infinium HD methylation protocol.
2017-10-10 | GSE86078 | GEO
Project description:Mouse models have been developed to investigate colorectal cancer etiology and evaluate new anti-cancer therapies. While genetically engineered and carcinogen-induced mouse models have provided important information with regard to the mechanisms underlying the oncogenic process, xenograft models remain the standard for the evaluation of new chemotherapy and targeted drug treatments for clinical use. However, it remains unclear if drug efficacy data obtained from xenograft models translate into clinically-relevant treatment modalities. In this study, we have generated a panel of 28 patient-derived colorectal cancer explants (PDCCEs), an extension of our previous work, by direct transplantation of human colorectal cancer (CRC) tissues into NOD-SCID mice. A comprehensive histological and molecular evaluation of PDCCEs and their corresponding patient tumor demonstrates that PDCCEs maintain histological features and global biology through multiple passages. Furthermore, we demonstrate that in vivo sensitivity of PDCCEs to oxaliplatin can predict patient outcomes. Our findings suggest that PDCCEs maintain similarity to the patient tumor from which they are derived and can serve as a reliable preclinical model that can be incorporated into future strategies to optimize individual therapy for patients with CRC. 28 human primary colorectal and 37 mouse derived colorectal explant tumors
2012-06-06 | E-GEOD-35144 | biostudies-arrayexpress
Project description:Background and aims Tumor genetic testing is indispensable in the management of primary and advanced colorectal cancer, with one-third of patients progressing despite standard care. We aimed to refine the indications for genomics-guided precision therapy. Methods We prospectively sequenced 869 tumors from Chinese patients with colorectal cancer and performed a comprehensive analysis of clinical and genomic profiles. The clinical significance of single mutation and co-occurring events was assessed in metastatic colorectal cancer (mCRC). The tumor immune microenvironment was evaluated by Immunoscore assay and single-cell sequencing. Results Single gene somatic mutations in BRAF and RBM10 were associated with shorter progression-free survival (PFS) in treatment-naive mCRC patients (BRAF: hazard ratio [HR] = 2.2 [95% CI, 1.1-4.4]; RBM10: HR= 6.8 [95% CI, 2.6-17.3]), and RBM10 remained a risk factor irrespective of the addition of bevacizumab to the chemotherapy regimens. KRAS mutations coexisting with those in AMER1 or APC were enriched in the metastatic cohort (26.23%), which had poor PFS and did not benefit from bevacizumab. 40 patients (4.6%) carried pathogenic or likely pathogenic germline alterations in the DNA damage repair pathway and 30% of them had double-hit events in the tumor with higher MSI scores. High tumor indel burden with MSI-high suggested a large number of tumor-infiltrating lymphocytes, whereas POLE-mutant with TMB-ultrahigh indicated a relatively quiescent immunophenotype. The heterogeneous genomic-immunological ecosystem was reflected in the divergent antigen presentation, immune checkpoint protein expression and responses of T cells to pembrolizumab treatment. Conclusion Integrated analysis of the clinical, genomic, and immunological profiles of colorectal cancer provides insights into prognostic stratification, drug response and potential clinical trials.
2023-01-10 | GSE222202 | GEO
Project description:We showed that a large number of genes and exons were deregulated in colorectal adenomas in comparison with colorectal normal mucosa.
2016-08-26 | GSE50592 | GEO
Project description:Patient-derived xenografts (PDX) and organoids (PDO) have been shown to model clinical response to cancer therapy. However, it remains challenging to use these models to guide timely clinical decisions for cancer patients. Here we used droplet emulsion microfluidics with temperature control and dead-volume minimization to rapidly generate thousands of Micro- Organospheres (MOS) from low-volume patient tissues, which serve as an ideal patient-derived model for clinical precision oncology. A clinical study of newly diagnosed metastatic colorectal cancer (CRC) patients using a MOS-based precision oncology pipeline reliably predicted patient treatment outcome within 14 days, a timeline suitable for guiding treatment decisions in clinic. Furthermore, MOS capture original stromal cells and allow T cell penetration, providing a clinical assay for testing immuno-oncology (IO) therapies such as PD-1 blockade, bispecific antibodies, and T cell therapies on patient tumors.
2022-09-01 | GSE184242 | GEO
Project description:Colorectal cancer (CRC) is one of the most prevalent tumors, with a high mortality rate. Nearly half of CRC patients develop metastasis, which accounts for as many as 90% of CRC-related deaths. In the metastasis process, cancer cells exhibit altered dependency on specific metabolic pathways and some of the metabolites discovered might be useful as potential diagnostic biomarkers. To identify metabolic pathway dependencies in CRC metastasis, mass spectrometry-based untargeted metabolomic analysis was performed in two pairs of CRC cell lines with different metastatic abilities. Each pair of cell lines was comprised of primary and metastatic colorectal cancer cell lines (SW480 vs. SW620; HT-29 vs. COLO 205). Relative levels of intracellular metabolites distinguished high-metastatic CRC cells from low-metastatic CRC cells.
2022-10-06 | ST002341 | MetabolomicsWorkbench
Project description:Metastasis is a complex process involving multiple steps. We were interested in the role of microRNAs (miRNAs) in the process of liver colonization by colorectal cancer cells. We hypothesized that the comparison between non-metastatic versus metastatic isogenic cell line should thus offer valuable insight to the molecular mechanisms involved in developing metastatic behavior. KM12C/KM12SM and SW480/SW620 are probably the best available models of isogenic cell lines differing in metastatic properties for colorectal cancer. Our first goal was to identify miRNAs that contribute to the metastatic traits of the isogenic colorectal cancer cell lines, KM12C/KM12SM and SW480/SW620. Total RNA was extracted from cells using the mirVana kit (Ambion). Total RNA (1 µg) from KM12C and SW480 (poorly metastatic) and KM12SM and SW620 (highly metastatic) cells was used to analyze the global miRNA expression profiling with TaqMan Megaplex human array A (v2.0) and B (v3.0) (Applied Biosystems).
2017-03-01 | GSE86302 | GEO