GRCh38 · COSMIC v91

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
Aristolochic acid in the etiology of renal cell carcinoma.
Paper ID
COSP42128
Authors
Hoang ML, Chen CH, Chen PC, Roberts NJ, Dickman KG, Yun BH, Turesky RJ, Pu YS, Vogelstein B, Papadopoulos N, Grollman AP, Kinzler KW and Rosenquist T
Affiliation
Ludwig Center for Cancer Genetics and Therapeutics and The Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center.
Journal
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2016
ISSN: 1538-7755
PMID: 27555084 (view at PubMed or Europe PMC)
Abstract
Background: Aristolochia species used in the practice of traditional herbal medicine contain aristolochic acid (AA), an established human carcinogen contributing to urothelial carcinomas of the upper urinary tract. AA binds covalently to genomic DNA, forming aristolactam (AL)-DNA adducts. We here investigated whether AA is also an etiologic factor in clear cell renal cell carcinoma (ccRCC).Methods: We conducted a population-based case-control study to investigate the linkage between Aristolochia prescription history, cumulative AA consumption, and ccRCC incidence in Taiwan (5,709 cases and 22,836 matched controls). The presence and level of mutagenic dA-AL-I adducts were determined in the kidney DNA of 51 Taiwanese ccRCC patients. The whole exome sequences of ccRCC tumors from ten Taiwanese ccRCC pateints with prior exposure to AA were determined.Results: Cumulative ingestion of more than 250 milligrams of AA increased risk of ccRCC (OR 1.25) and we detected dA-AL-I adducts in 76% of Taiwanese ccRCC patients. Further, the distinctive AA-mutational signature was evident in six of ten sequenced ccRCC exomes from Taiwanese patients.Conclusions: This study strongly suggests that AA contributes to the etiology of certain renal cell carcinomas.Impact: The present study offers compelling evidence implicating AA in a significant fraction of the RCC arising in Taiwan and illustrates the power of integrating epidemiological, molecular and genetic data in the investigation of cancer etiology.
Paper Status
Curated
Genes Analysed
2186
Mutated Samples
8
Total No. of Samples
8

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]

Table Information

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This is a whole exome/systematic screen paper and the negatives for this paper should be inferred.

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)