Aims
Professor Solomon's group's research currently concentrates on two areas, breast cancer and leukaemia. Much of her work centres on the genetics of breast cancer (especially where this is of an early onset, familial nature), and adopts several approaches.
First is a molecular analysis of the BRCA1 gene, which confers susceptibility to breast cancer in a proportion of women. This involves the investigation of the structure and expression of the gene product (including its role in sporadic breast and ovarian cancer), its regulation, and its behaviour as a tumour suppressor, and studies of transgenic mice with altered BRCA1 genes. Collaborative investigations of the structure of the RING finger domain of BRCA1 are also under way.
The second approach involves the analysis of further genes implicated in the genesis of breast cancer, which exist in close proximity to BRCA1. Molecular analysis of the function, expression and regulation of these genes is gradually disentangling their complex relationship with BRCA1.
Thirdly, a sib-pair genome search, which aims to identify regions of the genome containing further genes predisposing to breast cancer, is being undertaken with Prof Cathryn Lewis. Together with Prof Grimwade, she is continuing her work on the PML/RARA translocation underlying Acute Promyelocytic Leukaemia, the regulation of PML, and the structure of its RING finger domain.
AFFECT
Aims
- To collect breast tumour tissue, DNA, family history and clinical information from BRCA1 variant carriers whose gene change is thought to allow expression of an altered BRCA1 protein to test two assumptions currently used in variant classification research.
- To examine breast tumour tissue for features thought to predict BRCA1 variant pathogenicity.
- To define an algorithm for the determination of the pathogenicity of BRCA1 variants of unknown significance.
Protocol flow chart
Inclusion Criteria
Affected (breast cancer) carriers of BRCA1:
- Any missense (with a change of amino acid) variant (regardless of co-occuring UV in BRCA2).
- Any in-frame insertion or in-frame deletion variant
- BRCA1 185delAG and 188del11
- Variants in exon 24: (5677insA, 5622C>T (Arg1835ter) 5382insC)
What is involved
- Blood sample for DNA analysis
- Collection of family history and clinical data
- Collection and examination of paraffin embedded cancer tissue
- Follow up (by phone at approx. 2 and 5 years) to record any cancers that have occurred
Contact
Caroline Langman (Senior Research Nurse)
7th Floor Tower Wing,
Guy’s Hospital, Great Maze Pond,
London, SE1 9RT.
Tel: 020718 82603
Fax: 020718 82585
Email: caroline.langman@genetics.kcl.ac.uk
Collaborators and useful links
Funding bodies
- Medical Research Council
- Leukaemia Research Fund
- Arthritis Research Campaign (Versus Arthritis)
- Guy's & St Thomas charity