Exome Sequencing Identifies Rare Deleterious Mutations in DNA Repair Genes FANCC and BLM as Potential Breast Cancer Susceptibility Alleles
Menée sur 33 femmes issues de 15 familles affectées par un cancer du sein sans lien avec des mutations BRCA1/2, puis sur deux cohortes de 438 et 957 familles similaires, cette étude identifie, dans 6 familles, des mutations de deux gènes, FANCC et BLM, en association avec un risque accru de cancer du sein
Author Summary: Currently, we know that a woman who inherits a fault in one of two genes, BRCA1 or BRCA2, has a high risk of developing both breast and ovarian cancer. However, such faults account for only half of all families with a strong family history of breast cancer. In this study, we planned to identify new genes that may be associated with an increased risk of developing breast cancer by looking for faults in every gene in the blood DNA of multiple women with breast cancer from large families with a strong family history of the condition over multiple generations. We can then track which gene fault is present in all the women with breast cancer in that family and in other families, but is not found in the women who did not develop breast cancer or have no family history. Using this approach, we identified faults in two genes, Fanconi C and Bloom helicase, in six families. Faults in these genes appear to increase the risk of developing breast cancer. Both these genes work in a similar way as BRCA1 and BRCA2, and this highlights the importance of these functions in preventing breast cancer. Further studies need to be done to confirm our results.