In addition to the genes described above, plausible candidate genes exist in several of the newly associated regions. MUS81 at 11q13 has a key role in the maintenance of genomic stability and in DNA repair pathways37,38, and the cofilin gene (CFL1) is required for tumor cell motility and invasion, particularly in mammary tumors39,40. Several other genes have been associated with tumor aggressiveness; these include PTH1R at 3p21, FOXQ1 at 6p25, ARHGEF5 at 7q35 and MKL1 at 22q13. PTH1R is the receptor for PTHLH, encoded by a previously identified breast cancer susceptibility locus15. PTHLH is required for normal mammary gland function and has been shown to be involved in the metastasis of breast cancer cells to bone41,42. FOXQ1 encodes a transcription factor with a key role in cell proliferation and migration and in breast cancer metastasis43. Alterations in its expression level induce mesenchymal-epithelial transition44. Dysfunctional ARHGEF5 acts as an oncogene specific for human breast tissue, with a crucial role in tumorigenesis and metastasis in breast cancer45. MKL1 is also involved in tumor cell invasion and metastasis, particularly in human breast carcinoma46.
