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: 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: COSP45874
Authors: 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
Affiliation: Molecular Genetics Unit, Department of Laboratory Medicine, University Hospital of Pisa, Pisa, Italy.
Journal: Frontiers in genetics, 2018;9:397
ISSN: 1664-8021
PMID: 30283497 (view at PubMed or Europe PMC)
Abstract: 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 mre11, rad50, rad51, and msh6 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 msh2Δ strain; the neutral p.Y179C and the pathogenic p.I1766S variant induced gene reversion also, in the msh6Δ strain. These results imply a functional interaction between MMR and BRCA1 in modulating genome instability. We also performed a somatic mutational screening of MSH6, RAD50, MRE11A, and RAD51 genes in tumor samples from 34 patients and identified eight pathogenic or predicted pathogenic rare missense variants: four in MSH6, one in RAD50, one in MRE11A, and two in RAD51. 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: Curated
Genes Analysed: 24
Mutated Samples: 6
Total No. of Samples: 34

Mutation Matrix

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

Genes	Mutated Samples

Non-Mutant Genes	Gene Id (COSG)

Variants

Coding Mutations
Non-Coding Mutations
CNV & Expr
Methylation
Fusions

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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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

Mutant Samples
Non-Mutant 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)

GRCh38 · COSMIC v92