Large and genomic rearrangements in Danish high risk breast-ovarian cancer families

Thomas V. O. Hansen (1) , Lars Jønson (1) , Anders Albrechtsen (2) , Mette K. Andersen (3) , Bent Ejlertsen (4) , Finn C. Nielsen (1)

1 Department of Clinical Biochemistry [Rigshospitalet]
2 Section of Biostatistics [Copenhagen]
3 Department of Clinical Genetics, The Juliane Marie Center
4 Department of Oncology

germ-line mutations predispose to breast and ovarian cancer. Large genomic rearrangements of account for 0–36% of all disease causing mutations in various populations, while large genomic rearrangements in are more rare. We examined 642 East Danish breast and/or ovarian cancer patients in whom a deleterious mutation in and was not detected by sequencing using the multiplex ligation-dependent probe amplification (MLPA) assay. We identified 15 patients with 7 different genomic rearrangements, including a exon 5–7 deletion with a novel breakpoint, a exon 13 duplication, a exon 17–19 deletion, a exon 3–16 deletion, and a exon 20 deletion with a novel breakpoint as well as two novel exon 17–18 and exon 19 deletions. The large rearrangements in and accounted for 9.2% (15/163) of all and mutations in East Denmark. Nine patients had the exon 3–16 deletion in . By SNP analysis we find that the patients share a 5 Mb fragment of chromosome 17, including , indicating that the exon 3–16 deletion represents a Danish founder mutation.

Mots clés: Breakpoint; Danish founder mutation; Deletion; Duplication; MLPA; SNP array

Thomas V. O. Hansen, Lars Jønson, Anders Albrechtsen, Mette K. Andersen, Bent Ejlertsen, et al.. Large and genomic rearrangements in Danish high risk breast-ovarian cancer families. Breast Cancer Research and Treatment, 2008, 115 (2), pp.315-323. ⟨10.1007/s10549-008-0088-0⟩. ⟨hal-00478242⟩