Familial breast and or ovarian cancer eligibility statement Familial breast and or ovarian cancer inclusion criteria Multiplex cases: Proband is affected by invasive breast cancer (age <50) - 3 family members (FDR, SDR, TDR) affected by invasive breast cancer (average age of BCs <60). - Samples available and to be collected from >= 2 affected relatives Proband only recruitment: - Proband is affected by breast cancer (age <50) or ovarian cancer (any age). - Manchester Score of family >22 - Cases of ovarian cancer (any age) and breast cancer (<40) have been confirmed. - Ovarian cancers demonstrated to be invasive epithelial; mucinous and borderline tumours non-eligible (where histology available) - Family is not eligible for recruitment to the multiplex families breast cancer eligibility. - Samples to be supplied from: proband only. Unaffected individuals should not be recruited in this disorder. Familial breast and or ovarian cancer exclusion criteria Prior genetic testing guidance - Results should have been reviewed for all genetic tests undertaken, including disease-relevant genes in exome sequencing data. The patient is not eligible if they have a molecular diagnosis for their condition. - Genetic testing should continue according to routine local practice for this phenotype regardless of recruitment to the project; results of these tests must be submitted via the ‘Genetic investigations’ section of the data capture tool to allow comparison of WGS with current standard testing. PLEASE NOTE: The sensitivity of WGS compared to current diagnostic genetic testing has not yet been established. It is therefore important that tests which are clinically indicated under local standard practice continue to be carried out. Familial breast and or ovarian cancer prior genetic testing genes Testing as below is strongly recommended PRIOR TO RECRUITMENT to allow appropriate management of families with readily detectable mutations in known disease genes: - BRCA1 - BRCA2
Ellen McDonagh (Genomics England Curator)
Group: Other
Workplace: Other
Treena Cranston (Oxford)
Group: NHS Genomic Medicine Centre
Workplace: NHS diagnostic lab
Paul Pharoah (University of Cambridge)
Group: Other NHS organisation
Workplace: Research lab
Clare Turnbull (Queen Mary University London)
Group: GeCIP domain
Workplace: NHS clinical service
Ellen Thomas (Genomics England Curator)
Group: Other
Workplace: Other
Dmitrijs Rots (Children's Clinical University Hospital)
Group: Other
Workplace: Research lab
Arina Puzriakova (Genomics England Curator)
Group: Other
Workplace: Other
Lauma Freimane (Children's Clinical University Hospital)
Group: Other
Workplace: Other diagnostic lab
List | Entity | Reviews | Mode of inheritance | Details | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Green List (high evidence) |
ATM |
4 reviews1 green 1 red |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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Green List (high evidence) |
BRCA1 |
3 reviews3 green |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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Green List (high evidence) |
BRCA2 |
3 reviews3 green |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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Green List (high evidence) |
CHEK2 |
4 reviews2 red |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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Green List (high evidence) |
PALB2 |
4 reviews3 green |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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Green List (high evidence) |
PTEN |
1 review |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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Green List (high evidence) |
RAD51C |
3 reviews1 green 2 red |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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Green List (high evidence) |
RAD51D |
4 reviews1 green 2 red |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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Green List (high evidence) |
STK11 |
2 reviews1 red |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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Green List (high evidence) |
TP53 |
3 reviews2 green |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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Amber List (moderate evidence) |
ATRIP |
2 reviews1 green |
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown |
Sources
Phenotypes
Tags |
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Red List (low evidence) |
AR |
1 review1 red |
Not set |
Sources
Phenotypes
Tags |
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Red List (low evidence) |
BARD1 |
3 reviews1 green 1 red |
BIALLELIC, autosomal or pseudoautosomal |
Sources
Phenotypes
Tags |
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Red List (low evidence) |
BRIP1 |
3 reviews2 red |
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown |
Sources
Phenotypes
Tags |
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Red List (low evidence) |
CDH1 |
5 reviews2 green 1 red |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
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Red List (low evidence) |
EPCAM |
1 review1 red |
Not set |
Sources
Phenotypes
Tags |
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Red List (low evidence) |
ESR1 |
1 review1 red |
Not set |
Sources
Phenotypes
Tags |
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Red List (low evidence) |
MLH1 |
1 review1 red |
Not set |
Sources
Phenotypes
Tags |
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Red List (low evidence) |
MSH2 |
1 review1 red |
Not set |
Sources
Phenotypes
Tags |
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Red List (low evidence) |
MSH6 |
1 review1 red |
Not set |
Sources
Phenotypes
Tags |
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Red List (low evidence) |
MUTYH |
1 review1 red |
Not set |
Sources
Phenotypes
Tags |
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Red List (low evidence) |
NBN |
1 review1 red |
Not set |
Sources
Phenotypes
Tags |
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Red List (low evidence) |
PMS2 |
1 review1 red |
Not set |
Sources
Phenotypes
Tags |
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Red List (low evidence) |
PPM1D |
2 reviews2 red |
Not set |
Sources
Phenotypes
Tags |
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Red List (low evidence) |
RAD54L |
1 review1 red |
Not set |
Sources
Phenotypes
Tags |
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Red List (low evidence) |
RRAS2 |
1 review1 red |
Unknown |
Sources
Phenotypes
Tags |
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Red List (low evidence) |
XRCC2 |
1 review1 red |
Not set |
Sources
Phenotypes
Tags |
Many genes are robustly associated with breast cancer but with low penetrance and no clear clinical pathway. For now, the panel has been designed to identify mutations in genes which have high penetrance and therefore confer eligibility to screening. Further research will be done via GeCIP to look at the other genes on this panel and if robust evidence develops for diagnostic utility, a re-analysis will detect these mutations in all recruited participants with familial breast cancer.