GRCh38 · COSMIC v87


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.

Functional Interaction Between BRCA1 and DNA Repair in Yeast May Uncover a Role of RAD50, RAD51, MRE11A, and MSH6 Somatic Variants in Cancer Development.
Paper ID
Maresca L, Lodovichi S, Lorenzoni A, Cervelli T, Monaco R, Spugnesi L, Tancredi M, Falaschi E, Zavaglia K, Landucci E, Roncella M, Congregati C, Gadducci A, Naccarato AG, Caligo MA and Galli A
Molecular Genetics Unit, Department of Laboratory Medicine, University Hospital of Pisa, Pisa, Italy.
Frontiers in genetics 2018;9:397
In this study, we determined if BRCA1 partners involved in DNA double-strand break (DSB) and mismatch repair (MMR) may contribute to breast and ovarian cancer development. Taking advantage the functional conservation of DNA repair pathways between yeast and human, we expressed several BRCA1 missense variants in DNA repair yeast mutants to identify functional interaction between BRCA1 and DNA repair in BRCA1-induced genome instability. The pathogenic p.C61G, pA1708E, p.M775R, and p.I1766S, and the neutral pS1512I BRCA1 variants increased intra-chromosomal recombination in the DNA-repair proficient strain RSY6. In the <i>mre11, rad50, rad51</i>, and <i>msh6</i> deletion strains, the BRCA1 variants p.C61G, pA1708E, p.M775R, p.I1766S, and pS1215I did not increase intra-chromosomal recombination suggesting that a functional DNA repair pathway is necessary for BRCA1 variants to determine genome instability. The pathogenic p.C61G and p.I1766S and the neutral p.N132K, p.Y179C, and p.N550H variants induced a significant increase of reversion in the <i>msh2</i>Δ strain; the neutral p.Y179C and the pathogenic p.I1766S variant induced gene reversion also, in the <i>msh6</i>Δ strain. These results imply a functional interaction between MMR and BRCA1 in modulating genome instability. We also performed a somatic mutational screening of <i>MSH6, RAD50, MRE11A</i>, and <i>RAD51</i> genes in tumor samples from 34 patients and identified eight pathogenic or predicted pathogenic rare missense variants: four in <i>MSH6</i>, one in <i>RAD50</i>, one in <i>MRE11A</i>, and two in <i>RAD51</i>. Although we found no correlation between BRCA1 status and these somatic DNA repair variants, this study suggests that somatic missense variants in DNA repair genes may contribute to breast and ovarian tumor development.
Paper Status
Genes Analysed
Mutated Samples
Total No. of Samples

Mutation Matrix

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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


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


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


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.

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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.


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


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)