Copy number variations are not modifiers of phenotypic expression in a pair of identical twins carrying a mutation

A. Lasa (1) , T. Ramón y Cajal (2) , G. Llort (3) , J. Suela (4) , J. C. Cigudosa (4) , M. Cornet (1, 5) , C. Alonso (2) , A. Barnadas (2) , M. Baiget (1, 5, 6)

1 Genetics Department, Hospital Sant Pau
2 Clinical Oncology Department, Hospital Sant Pau
3 Clinical Oncology Department
4 NIMGenetics
5 U-705 CIBERER
6 Servicio de Genética

Mutations in and genes confer a high risk of breast and ovarian cancer but the incomplete penetrance of these mutations suggests that other genetic and/or environmental factors may modify this risk. We present a family where all affected members carried a mutation in the gene and the index case had suffered from cancer twice in the last 27 years, whereas her monozygotic twin sister, also a carrier of the mutation, remained healthy. As copy number variants (CNVs) contribute to phenotypic diversity, a comparative genomic hybridization array (CGH) was performed to see whether the differences in the CNV profile were a modifier factor of the phenotype in our monozygotic twins. Our results show that differences in the CNVs profile were not the cause of the extremely variable penetrance observed in our MZ twin. The search for an explanation should not therefore be limited to genetic changes at the level of the DNA sequence.

Mots clés: BRCA1; BRCA2; Copy number variation; Monozygotic twins

A. Lasa, T. Ramón y Cajal, G. Llort, J. Suela, J. C. Cigudosa, et al.. Copy number variations are not modifiers of phenotypic expression in a pair of identical twins carrying a mutation. Breast Cancer Research and Treatment, 2010, 123 (3), pp.901-905. ⟨10.1007/s10549-010-0877-0⟩. ⟨hal-00523666⟩