Genomic Landscape of Colorectal Cancer in a Multi-Ancestry Cohort
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PROVIDER: PRJNA1035236 | ENA |
REPOSITORIES: ENA
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Project description:Genomic Landscape of Colorectal Cancer in a Multi-Ancestry Cohort
| PRJNA1035237 | ENA
Project description:The genomic and immune landscapes of prostate cancer differ by self-identified race. However, few studies have examined the genome-wide copy number landscape and immune content of matched cohorts with genetic ancestry data and clinical outcomes. Here, we assessed prostate cancer somatic copy number alterations (sCNA) and tumor immune content of a grade-matched, surgically-treated cohort of 145 self-identified Black (BL) and 145 self-identified white (WH) patients with genetic ancestry estimation. A generalized linear model adjusted with age, pre-operative PSA, and Grade Group and filtered for germline copy number variations (gCNV) identified 143 loci where copy number varied significantly by percent African ancestry, clustering on chromosomes 6p, 10q, 11p, 12p, and 17p. Multivariable Cox regression models adjusted for age, pre-operative PSA levels, and Grade Group revealed that chromosome 8q gains (including MYC) were significantly associated with biochemical recurrence and metastasis, independent of genetic ancestry. Finally, regulatory T-cell density in BL and WH patients was significantly correlated with percent genome altered, and these findings were validated in the TCGA cohort. Taken together, our findings identify specific sCNA linked to genetic ancestry and outcome in primary prostate cancer and demonstrate that regulatory T-cell infiltrate varies by global sCNA burden in primary disease.
2023-05-31 | GSE221219 | GEO
Project description:Response to drug therapy in individual colorectal cancer (CRC) patients is associated with tumor biology. Here we describe the genomic landscape of tumor samples of a homogeneous well-annotated series of patients with metastatic CRC of two phase III clinical trials, CAIRO and CAIRO2. DNA copy number aberrations of 349 patients are determined. Within three treatment arms, 194 chromosomal sub-regions are associated with progression free survival PFS (uncorrected single-test p-values < 0.005). These sub-regions are filtered for effect on mRNA expression, using an independent data set from The Cancer Genome Atlas (TCGA) which returned 171 genes. Three chromosomal regions are associated with a significant difference in PFS between treatment arms with or without irinotecan. One of these regions, 6q16.1-q21, correlates in vitro with sensitivity to SN-38, the active metabolite of irinotecan. This genomic landscape of metastatic CRC reveals a number of DNA copy number aberrations associated with response to drug therapy. aCGH data of colorectal cancers of patients from 2 clinical trials (CAIRO, CAIRO2). 105 patients were treated with capecitabine first line (CAIRO arm A), 111 patients were treated with capecitabine and irinotecan first line (CAIRO arm B), and 133 patients were treated with capecitabine, oxaliplatin and bevacizumab (CAIRO2 arm A).
2014-11-14 | E-GEOD-36864 | biostudies-arrayexpress
Project description:The Genomic Landscape of Interval Colorectal Cancers
| PRJNA892207 | ENA
Project description:The Genomic Landscape of Interval Colorectal Cancers
| PRJNA892208 | ENA
Project description:Purpose: Examine H3K27ac enhancer and super-enhancer landscape differences between primary colorectal carcinoma and adjacent normal mucosa towards the identification of novel downstream targets. Methods: H3K27ac ChIP-seq and RNA-seq were performed on fresh primary colorectal carcinoma samples and normal colonic mucosa, from human patient samples. Results: We identified 2026 total super-enhancers in our cohort, between primary colorectal and normal mucosa. We quantified differences in H3K27ac signal within this space, between tumor and normal, and identified putative downstream target genes through integration with sample matched RNA-seq using a positive linear correlation model to identifty putative target genes.
2022-08-03 | GSE166254 | GEO
Project description:Response to drug therapy in individual colorectal cancer (CRC) patients is associated with tumor biology. Here we describe the genomic landscape of tumor samples of a homogeneous well-annotated series of patients with metastatic CRC of two phase III clinical trials, CAIRO and CAIRO2. DNA copy number aberrations of 349 patients are determined. Within three treatment arms, 194 chromosomal sub-regions are associated with progression free survival PFS (uncorrected single-test p-values < 0.005). These sub-regions are filtered for effect on mRNA expression, using an independent data set from The Cancer Genome Atlas (TCGA) which returned 171 genes. Three chromosomal regions are associated with a significant difference in PFS between treatment arms with or without irinotecan. One of these regions, 6q16.1-q21, correlates in vitro with sensitivity to SN-38, the active metabolite of irinotecan. This genomic landscape of metastatic CRC reveals a number of DNA copy number aberrations associated with response to drug therapy.
2014-11-14 | GSE36864 | GEO
Project description:We measured genomic responses to active vitamin D, 1α,25-dihydroxyvitamin D (1,25D), in colonic organoids from individuals of African and European ancestry. Given protective effects of 1,25D for gastrointestinal conditions such as colorectal cancer, organoid cultures enabled evaluation of condition-specific responses in relevant target tissue. We found significant alterations in transcriptional and chromatin accessibility responses to 1,25D treatment, including some with ancestry-associated differences, and also elucidated the role of cis-genetic variance on treatment responses. Integration of genomic profiling with genetic mapping found an indel that explains ancestry-associated differences in the regulation of POLB response to 1,25D which showed signals of positive natural selection.
2026-01-01 | GSE295961 | GEO
Project description:Epigenomics landscape of colorectal cancer
| PRJNA563919 | ENA
Project description:Characterization of ancestry-linked peptide variants in disease-relevant patient tissues represents a foundational step to connect patient ancestry with molecular disease pathogenesis. Nonsynonymous single nucleotide polymorphisms (SNPs) encoding missense substitutions within tryptic peptides exhibiting high allele frequencies in European, African, and East Asian populations, termed peptide ancestry informative markers (pAIMs), were prioritized from 1000 genomes. In silico analysis shows that as few as 20 pAIMs can determine ancestry proportions similarly to >260K SNPs (R2=0.9905). Multiplexed proteomic analysis of >100 human endometrial cancer cell lines and uterine leiomyoma (ULM) tissues combined resulted in the quantitation of 62 pAIMs that correlate with self-described race and genotype-confirmed patient ancestry. Candidates include a D451E substitution in GC vitamin D-binding protein previously associated with altered vitamin D levels in African and European populations. These efforts describe a generalized set of markers for proteoancestry assessment that will further support studies investigating the impact of ancestry on the human proteome and how this relates to the pathogenesis of uterine neoplasms.
2022-02-16 | PXD029323 | Pride