Ontology highlight
ABSTRACT:
PROVIDER: PRJNA772782 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Colorectal cancer arises in part from the cumulative effects of multiple gene lesions. Recent studies in selected cancer types have revealed significant intra-tumor genetic heterogeneity and highlighted its potential role in disease progression and resistance to therapy. We hypothesized the existence of significant intra-tumor genetic heterogeneity in rectal cancers involving variations in localized somatic mutations and copy number abnormalities. Two or three spatially disparate areas from each of six rectal tumors were dissected and subjected to next-generation whole exome DNA sequencing, Oncoscan SNP arrays, and targeted confirmatory sequencing and analysis. The resulting data were integrated to define subclones using SciClone. Mutant-allele tumor heterogeneity (MATH) scores, mutant allele frequency correlation, and mutation percent concordance were calculated, and Copy number analysis including measurement of correlation between samples was performed.
2015-09-24 | GSE73365 | GEO
Project description:Background: Lung carcinoma-in-situ (CIS) lesions are the pre-invasive precursor to lung squamous cell carcinoma. However, only half progress to invasive cancer in three years, while a third spontaneously regress. Whether modern molecular profiling techniques can identify those pre-invasive lesions that will subsequently progress and distinguish them from those that will regress is unknown. Methods: Progressive and regressive CIS lesions were laser-captured and their genome, epigenome and transcriptome interrogated. We analysed 83 progressive lesions, 41 regressive and 33 normal epithelial control samples. DNA methylation and gene expression profiles were further validated using publicly available lung cancer data. Results: Somatic mutation burden was higher in progressive lesions than regressive CIS lesions, across base substitutions, rearrangements, insertions and deletions. Driver mutations were present in both progressive and regressive CIS lesions, but were more numerous in progressive cases. Progressive and regressive CIS lesions had distinct epigenomic and transcriptional profiles, with a strong chromosomal instability signature. Gene expression, methylation and copy number profiles can all predict accurately which CIS lesions will progress to lung cancer. Conclusion: Pre-invasive CIS lesions that will subsequently progress to invasive lung cancer can be distinguished from those that will regress using molecular profiling. Progression is associated with a strong chromosomal instability signature. These findings inform the development of novel therapeutic targets.
2019-01-01 | GSE108082 | GEO
Project description:Colorectal adenomas are cancer precursor lesions of the large bowel. In these preinvasive lesions, a vast array of genomic and epigenomic changes have been detailed, but the consequence of these molecular alterations on the effectors of biological function (proteins) has not been comprehensively explored.
2014-04-03 | PXD000445 | Pride
Project description:Colorectal adenomas are benign precursor lesions of colorectal cancer (CRC) that arise from normal epithelium1. The prevalence of adenomas in the large intestine is much higher than the incidence of cancer implying that the majority of adenomas will never progress to CRC4. In clinical practice, adenomas detected during colonoscopy are completely removed, and consequently the natural history of disease disrupted. Based on the prevalence of focal cancer in endoscopically removed adenomas, it is estimated that only 5% of adenomas will eventually progress to CRC. The aim of the present study was to characterize adenomas at low and high risk of progressing to cancer by extensive molecular profiling at DNA, RNA, and protein level, allowing to examine the biological processes in which they differ and to discover putative drivers of early colorectal tumor development.
2019-08-22 | PXD012254 | Pride
Project description:Laterally spreading tumors (LSTs) are colorectal adenomas that develop into extremely large lesions but rarely become malignant. Elucidating their molecular profiles, and how these contrast with colorectal cancer (CRC), offers the opportunity to understand their biology and how they are able to grow to such large lesions without progressing to cancer. Profiling of 11 LSTs with multiple genome-wide approaches showed mutation rates comparable with microsatellite stable CRCs at 2.4 versus 2.6 mutations per megabase respectively, however copy number alterations are infrequent (averaging 1.5 per LST). Only 28.5% of genes with promoter CpG island hypermethylation showed >2-fold downregulation of expression in LST tissue relative to paired normal mucosa. Integration of genetic and epigenetic data identified driver genes not previously implicated in colorectal neoplasia (ANO5, MED12L, EPB41L4A, RGMB, SLITRK1, NRXN1, ANK2), including genes targeted by both genetic and epigenetic alterations. Alterations to pathways commonly mutated in CRCs, namely the p53, PI3K and TGFb pathways, are rare. Instead LST-altered genes converge on axonal guidance, Wnt and actin cytoskeleton signalling. Non-granular morphology, which is associated with an elevated risk of cancer, correlates with low frequencies of epigenetic inactivation and KRAS mutations and the hyperactivation of CXCR4 signalling. These data show that mutation load is a poor predictor of invasive potential and that genomic structural aberrations or alterations in key pathways is important in progression to cancer. By integrating genetic, epigenetic and transcriptional data this study identifies novel genes important in early colorectal neoplasia.
2016-11-12 | GSE77635 | GEO
Project description:An investigation into genetic mutation of primary lesions in colorectal cancer patients with synchronous liver metastases
2023-01-03 | PRJEB58641 | EVA
Project description:DNA methylation profiling of gastric cancer and precursor lesions
| PRJNA525674 | ENA
Project description:Purpose: To identify the contribution of PRDM2 c.4459delA mutation to colorectal tumorigenesis Methods: We employed rAAV-mediated genome editing to correct somatic PRDM2 c.4459delA mutation in homozygously mutated cell line. Using next-generation sequencing we have compared transcriptional profile of parental and PRDM2-corrected cells. Results: RNA-seq profiling revealed that several hallmark cancer gene sets are affected by PRDM2 c.4459delA
2018-02-22 | GSE80033 | GEO
Project description:<p>Molecular profiling for somatic mutations that predict response to anti-EGFR therapy in colorectal cancer (CRC) has become standard practice. However, abundant tissue from metastatic lesions is not always available from patients with metastatic CRC. Concerns involving genetic heterogeneity between primary and metastatic lesions have called into question the suitability of profiling primary tumors in patients with metastatic disease. Further, the identification of discordant mutations between matched primary and metastatic tumors would be of biological interest for the delineation of biomarkers of tumor progression and metastasis.</p> <p>To explore the degree of genetic heterogeneity between matched primary and metastatic tumors in CRC, we performed whole genome sequencing of four patient "trios" comprised of a primary colon tumor, a liver metastasis, and matched normal (non-cancerous) tissue. Somatic mutations and indels were called in each tumor and compared between primary and metastatic lesions.</p>
| phs000790 | dbGaP
Project description:We performed whole exome sequencing and copy number analysis for 15 triplets, each comprising normal colorectal tissue, primary colorectal carcinoma, and its synchronous matched liver metastasis. We analyzed the similarities and differences between primary colorectal carcinoma and matched liver metastases in regards to somatic mutations and somatic copy number alterationss (SCNAs). The genomic profiling demonstrated mutations in APC(73%), KRAS (33%), ARID1A and PIK3CA (6.7%) genes between primary colorectal and metastatic liver tumors. TP53 mutation was observed in 47% of the primary samples and 67% in liver metastatic samples. The grouped pairs, in hierarchical clustering showed similar SCNA patterns, in contrast to the ungrouped pairs. Many mutations (including those of known key cancer driver genes) were shared in the grouped pairs. The ungrouped pairs exhibited distinct mutation patterns with no shared mutations in key driver genes. Four ungrouped liver metastasis samples had mutations in DNA mismatch repair genes along with hypermutations and a substantial number of copy number of alterations. Genomically, colorectal and metastatic liver tumors were very similar. However, in a subgroup of patients, there were genetic variations in liver metastases in the loss of DNA mismatch repair genes.
2014-03-01 | GSE53799 | GEO