Introduction ATM 1 ATM http://chromium.liacs.nk/lovd/ ATM 2 3 ATM 4 ATM ATM ATM 5 6 ATM 2 7 8 9 ATM ATM Methods Patients n n 10 11 Genomic DNA isolation 12 Mutation analysis ATM ATM Statistical analysis 13 Results and discussion ATM germline mutations ATM ATM ATM ATM 10 ATM D1853N ATM missense mutation spectrum ATM 1 ATM Table 1 ATM Missense variants Amino acid change n n a 37C>T R13C  1 10 146C>G S49C 5 5 database 162T>C Y54H 2 1 4 14 378A>T D126E  1 database 1009C>T R337C  1 Novel 1132A>G S377G  1 Novel 1229T>G V410A 2 1 4 1810C>T P604S 1  database 2119T>C S707P 7 8 database 2276G>A  S759N   Novel 2336T>C M779T  1 Novel 2414G>A R805Q 2  Novel 2572T>C F858L 4 3 database 2650C>T P884S 1   2650C>T P884S 1  Novel 2614C>T P872S   15 3161C>G P1054R 8 13 database 3925G>A A1309T 1 1 16 4138C>T H1380Y 1  database 4258C>T L1420F 5 4 database 4324T>C Y1442H  2 Novel 4362A>C K1454N  1 database 4477C>G L1493V 1  Novel 4664T>A L1555H  1 Novel 4722G>T L1574F 1  Novel 5044G>T D1682Y 1  database 5071A>C S1691R 2 2 database 5557G>A b D1853N 35 49 database 5558A>T D1853V 3 1 database 5741A>G D1914G   Novel 6067G>A G2023R 1  database 6820G>A A2274T 1  database 6919C>T L2307F 1  14 7446G>A M2482I 1  Novel 7874A>G D2625G  1 Novel 8659C>G H2887D  1 Novel Truncating mutations IVS10-6T>G 419X 1 2 10 17 1563delAG 521X  1 database 1660delA 554X 1  Novel IVS14 + 2T>G del 601-633 1  database 2572insT F858X  1 Novel 3115A>T R1039X 1  Novel a  http://chromium.liacs.nk/lovd/ b  ATM ATM ATM 18 20 ATM missense mutations and contralateral breast cancer ATM 2 n ATM 2 ATM ATM n ATM ATM ATM Table 2 ATM Breast cancer patients with n n n ATM a  55: 51 missense and 4 truncating 52: 48 missense and 4 truncating ATM 91 (21%) 45 (18%) 46 (23%) ATM 85 (19%) 43 (17%) 42 (21%) ATM 3 2 1 One truncating and one missense variant 5 2 3 Double missense variants 11 8 3 a  Association with radiation treatment ATM 21 BRCA1, BRCA2, CHEK2 ATM ATM ATM p ATM ATM 22 24 ATM ATM 22 ATM ATM p p The suggestion of a shorter induction period of RT-associated breast cancer in patients, who carry an ATM missense mutation, while the proportion of patients with missense variants was similar in CBC and UBC cases, might be attributable to a different spectrum of mutations in those patients who developed CBC. A big challenge in such a study remains to assess which particular missense mutations have an impact on ATM function. Large association studies, as performed by the Breast Cancer Association Consortium (coordinated by Doug Easton and Paul Pharoah, Cambridge), and functional studies are clearly necessary to determine the importance of particular variants and their contribution to the breast cancer risk.