The Genetics of Breast Cancer 
and Head & Neck Paragangliomas

Past & Present research goals

Previous work:

1. Breast Cancer:
• Linkage analysis in ~200 well-defined Dutch breast cancer families
• Loss of heterozygosity analysis in inherited breast tumors
• Loss of heterozygosity mapping of 16q in sporadic breast tumors
• Mutation screening of BRCA1 and BRCA2 in breast cancer families
• Mutation screening of BRCA1 and BRCA2 in consecutively collected series of breast cancer cases
2. Head & Neck Paragangliomas:
• Linkage analysis in ~30 paraganglioma families
• Loss of heterozygosity analysis in microdissected and flow-sorted paragangliomas
• Mutation screening of SDHD in familial and sporadic cases

Present research goals:

1. Breast Cancer:
• A linkage search for BRCA3
• A search for genetic factors that may modify the risk conferred by BRCA1 and BRCA2 by candidate gene analysis
• Identifying the tumor suppressor gene(s) targeted by LOH on 16q
• The analysis of a mouse model carrying a C-terminally truncated allele of Brca1
• The development of a functional assay for BRCA1 and BRCA2 mutations
2. Head & Neck Paragangliomas:
• Mutation analysis of SDHD in sporadic paraganglioma (in germline and in the tumors)
• The development of a mouse model carrying a null allele of SDHD
• Identification of the gene-defect mapping to PGL2 on 11q13
• Ultrastructural and biochemical analysis of the role of mitochondria in the genesis of paraganglioma in inherited patients