GRCh38 · COSMIC v92

Overview

This section shows a general overview of information for the selected study (COSU identifier) or publication (COSP identifier). Studies may have been performed by the Sanger Institute Cancer Genome Project, or imported from the ICGC/TCGA. You can see more information on the help pages.

Reference
Dynamics of genome alterations in Crohns disease associated colorectal carcinogenesis.
Paper ID
COSP45588
Authors
Hirsch D, Wangsa D, Zhu YJ, Hu Y, Edelman DC, Meltzer PS, Heselmeyer-Haddad K, Ott C, Kienle P, Galata C, Horisberger K, Ried T and Gaiser T
Affiliation
Institute of Pathology, Medical Faculty Mannheim/Heidelberg University.
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research, 2018
ISSN: 1078-0432
PMID: 29967250 (view at PubMed or Europe PMC)
Abstract
Purpose: Patients with inflammatory bowel diseases, i.e., ulcerative colitis (UC) and Crohn's disease (CD), face an increased risk of developing colorectal cancer (CRC). Evidence, mainly from UC, suggests that TP53 mutations represent an initial step in the progression from inflamed colonic epithelium to CRC. However, the pathways involved in the evolution of CRC in CD patients are poorly characterized.Here, we analyzed 73 tissue samples from 28 patients with CD-CRC, including precursor lesions, by targeted next generation sequencing of 563 cancer-related genes and array-based comparative genomic hybridization. The results were compared to 24 sporadic CRCs with similar histomorphology (i.e., mucinous adenocarcinomas), and to The Cancer Genome Atlas data.Results: CD-CRCs showed somatic copy number alterations (SCNAs) similar to sporadic CRCs with one notable exception: the gain of 5p was significantly more prevalent in CD-CRCs. CD-CRCs had a distinct mutation signature: TP53 (76% in CD-CRCs versus 33% in sporadic mucinous CRCs), KRAS (24% versus 50%), APC (17% versus 75%), and SMAD3 (3% versus 29%). TP53 mutations and SCNAs were early and frequent events in CD progression, while APC, KRAS and SMAD2/4 mutations occurred later. In four CD-CRC patients, at least one mutation and/or SCNAs were already present in non-dysplastic colonic mucosa, indicating occult tumor evolution.Conclusions: Molecular profiling of CD-CRCs and precursor lesions revealed an inflammation-associated landscape of genome alterations: 5p gains and TP53 mutations occurred early in tumor development. Detection of these aberrations in precursor lesions may help predicting disease progression and distinguishes CD-associated from sporadic colorectal neoplasia.
Paper Status
Curated
Genes Analysed
2515
Mutated Samples
65
Total No. of Samples
69

Mutation Matrix

This section shows the correlation plot between the top 20 genes and samples. There is more information in our help pages.

Genes

This table shows genes with mutations in the selected study/paper [more details]
Genes Mutated Samples
This table shows genes without mutations in the selected study/paper [more details]
Non-Mutant Genes Gene Id (COSG)

Variants

This tab shows genes with mutations in the selected study/paper [more details]

Genes Samples CDS Mutation AA Mutation

This tab shows non coding variant in the selected study/paper [more details]

Sample ID Sample Name ID NCV Annotation Zygosity Chromosome Genome start Genome stop Genome version Strand WT seq Mut seq FATHMM-MKL

This tab shows the gene expression and copy number variation data for this study [more details]

Table Information

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The table currently shows only high value (numeric) copy number data. Copy number segments are excluded if the total copy number and minor allele values are unknown.

Click here to include all copy number data. For more detailed information about copy number data and gain/loss definitions click here.

Sample Gene Expression Expr Level (Z-Score)

Over Expressed; Z-Score > 2.0

Under Expressed; Z-Score < -2.0

Normal; Z-Score within the range -2.0 to 2.0

CN Type Minor Allele Copy Number CN Segment Posn. Average Ploidy

1. N/A represents cases where the average ploidy value is not available( mostly ICGC samples). For some TCGA samples where the minor allele information is not available the average ploidy value could not be calculated.

2. For TCGA samples, the ASCAT algorithm was used to calculate the average ploidy.

3. For CGP samples, the PICNIC algorithm was used to calculate the average ploidy.

CNV

This table lists the samples in the selected study which have low/high methylation for each gene. [more details]

No data

This tab shows the fusion mutations observed in this sample [more details]

Gene Sample Name Id Sample(COSS) CDS Mutation Somatic status Zygosity Validated Type

Samples

This table shows mutated samples in the selected study/paper.

Sample Name Mutation Count

This table shows samples without mutations in the selected study/paper.

Non-Mutant Samples Sample Id (COSS)