Recurrent mutation testing of BRCA1 and BRCA2 in Asian breast cancer patients identify
carriers in those with presumed low risk by family history
Breast Cancer Research and Treatment
Peter Choon Eng Kang1,9, Sze Yee Phuah1,9, Kavitta Sivanandan1,9, In Nee Kang1,9, Eswary
Thirthagiri1, Jian Jun Liu2, Norhashimah Hassan1,3, Sook-Yee Yoon1, Meow Keong Thong4,
Miao Hui5, Mikael Hartman5,6, Cheng Har Yip7,8, Nur Aishah Mohd Taib3,8 and Soo Hwang Teo
1,3,10
1Cancer
Research Initiatives Foundation, Sime Darby Medical Centre, Subang Jaya, Malaysia
2Genome
Institute of Singapore, Singapore
3University
Malaya Cancer Research Institute, Faculty of Medicine, University Malaya, Kuala
Lumpur, Malaysia
4Department
5Saw
of Paediatrics, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia
Swee Hock School of Public Health and Department of Surgery, National University of
Singapore, Singapore
6Department
7Sime
Darby Medical Centre, Subang Jaya, Malaysia
8Department
9Joint
of Medical Epidemiology and Biostatistics, Karolinska Institute, Sweden
of Surgery, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia
first authors
10Corresponding
author
Soo Hwang Teo: [email protected]
Online Resource 1A: BRCA1 mutations tested
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
Mutation (BIC)
180 delA
185 delAG
185 insA
269 delA
582 C>T
589 delCT
735 C>T
804 delT
969 C>T
1017 G>T
1100 delAT
1129 delA
1173 G>T
1223 delA
1323 G>T
1510 delC
1523 delG
1966 ins7
2189 del2
2371 del2
2430 insC
2509 delAA
2732 insT
2754 G>T
2790 delT
2846 insA
2885 delA
3241 C>G
3300 delA
3378 delG
3407 del2
3478 del5
3672 G>T
3867 G>T
3874 del4
3889 del2
3975 delA
4267 C>G
4377 C>T
4446 C>T
4491 C>T
4731 C>T
4920 A>T
5370 C>T
5447 insC
5454 delC
5589 del8
5622 C>T
IVS 3+1 G>T
IVS 3+2 delT
IVS 4-1 G>C
IVS 5+1 G>T
IVS 5-12 A>G
IVS 7-15 del10
IVS 21+1 G>C
Mutation (HGVS)
c.61 delA
c.68_69 delAG
c.66 dupA
c.150 delA
c.463 C>T
c.470_471 delCT
c.616 C>T
c.685 delT
c.850 C>T
c.898 G>T
c.981_982 delAT
c.1016 delA
c.1054 G>T
c.1104 delA
c.1204 G>T
c.1392 delC
c.1405delG
c.1847_1853 insAAGTCTT
c.2070_2071delAA
c.2253_2254 delGT
c.2311 insC
c.2390_2391 delAA
c.2617 dupT
c.2635 G>T
c.2671 delT
c.2727 insA
c.2766 delA
c.3122 C>G
c.3181 delA
c.3262 delG
c.3288_3289 delAA
c.3359_3363 delTTAAT
c.3553 G>T
c.3748 G>T
c.3756_3759 delGTCT
c.3770_3771 delAG
c.3856 delA
c.4148 C>G
c.4258 C>T
c.4327 C>T
c.4372 C>T
c.4612 C>T
c.4801 A>T
c.5251 C>T
c.5328 dupC
c.5335 delC
c.5470_5477del8
c.5503 C>T
c.134+1 G>T
c.134+2 delT
c.135-1 G>C
c.212+1 G>T
c.213-12 A>G
c.442-15 del10
c.5332+1 G>C
AA change
STOP 22
STOP 39
STOP 40
STOP 68
Q155X
S157X
Q206X
STOP 233
Q284X
E300X
C328X
STOP 340
E352X
STOP 373
E402X
STOP 474
STOP 474
STOP 626
STOP 692
STOP 760
STOP 776
STOP 799
STOP 902
E879X
STOP 892
STOP 914
STOP 999
S1041X
I1061X
STOP 1108
STOP 1101
STOP 1130
E1185X
E1250X
STOP 1262
STOP 1265
STOP 1306
S1383X
Q1420X
R1443X
Q1458X
Q1538X
K1601X
R1751X
STOP 1829
STOP 1792
STOP 1826
R1835X
Population/Country
Indian/Malaysia
Indian/Malaysia, Singapore
Various
Indian/Malaysia
Chinese/China
Chinese/Malaysia
Chinese/China
Indian/Singapore
Indian/Malaysia
Singapore
Chinese/Malaysia
Chinese/Hong Kong
Indian/Malaysia
Chinese/Malaysia
Malay/Malaysia
Chinese/Singapore
Chinese/Singapore
Malaysia
Chinese/Malaysia
Chinese/Hong Kong
Chinese/Singapore
Japanese/Japan
Chinese/Singapore
Chinese/Malaysia,Hong Kong
Chinese/China
Malay/Singapore
Indian/Singapore
Japanese/Japan
Thai/Thailand
Chinese/Singapore
Malaysia
Chinese/China
Indian/India
Indian/India
Chinese/China
Indian/Pakistan
Malay/Malaysia
Chinese/Malaysia
Chinese/Malaysia
Chinese/Singapore
Chinese/Hong Kong
Filipino/Philippines
Chinese/Singapore
Indian/Malaysia
Malay/Malaysia
Filipino/Philippines
Chinese/China
Filipino/Philippines
Chinese/Malaysia
Chinese/Malaysia
Indian/Malaysia
Indian/India
Various
Chinese/Singapore
Chinese/China
References
[6]
[6, 30, 31]
[6, 31]
Novel
[32]
[6, 24]
[32]
BIC
Novel
[6, 26]
[21, 33]
[6, 34]
Novel
[6]
[35]
[35]
BIC
[33]
[35]
[36]
[35]
[21, 37]
[32]
[38]
[38]
[39]
[40]
[35]
[41]
[42]
[43]
[44]
[31]
Novel
Novel
Novel
[35]
[24]
[45]
[30]
[6, 46]
[23]
[45]
[26]
[45]
[6]
[6]
[6]
[47]
BIC
[30]
[26]
Online Resource 1B: BRCA2 mutations tested
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
Mutation (BIC)
490 delCT
1037C>G
1184 insA
2001 del4
2041 delA
2041 insA
2670 delC
2699 del6
2822 del4
2864 delCT
3036delACAA
3337 C>T
3423del4
3827del2
3972del4
4093del4
4242 insGG
4265 delCT
Mutation (HGVS)
c.262_263delCT
c.809C>G
c.956_957 insA
c.1773_1776 del4
c.1813_1813 delA
c.1813_1814 insA
c.2442_2442 delC
c.2471_2476delTAAATG
c.2596_2599 delGAAA
c.2636_2637 delCT
c.2808_2811delACAA
c.3109 C>T
c.3195_3198delTAAT
c.3599_3600delGT
c.3744_3747delTGAG
c.3865_3868delAAAT
c.4014_4015insGG
c.4037_4038delCT
AA change
STOP 99
S270X
STOP 326
STOP 612
STOP 613
STOP 615
STOP 824
STOP 824
STOP 872
STOP 879
STOP 958
Q1037X
STOP 1075
STOP 1200
STOP 1257
STOP 1291
STOP 1374
STOP 1350
19
20
21
22
23
4379 delT
5227 insT
5242 insT
5301 insA
5802del4
c.4151_4151delT
c.4999_5000insT
c.5014_5015insT
c.5073_5074 insA
c.5576_5579delTTAA
STOP 1387
STOP 1676
STOP 1676
STOP 1694
STOP 1861
24
5873 C>A
c.5645 C>A
S1882X
25
26
27
28
29
30
31
32
32
33
5950 delCT
6174delT
6180 insA
6195 insA
6553 delGT
6769G>T
6862 del4
6901 delA
6943 G>T
7051_7053
delGAG
7361 C>G
7786 C>T
8462 del4
9097 C>T
9118 insA
9143 delT
9187 del4
9189 del4
9325 delA
9326 insA
IVS15+1G>A
c.5722_5723 delCT
c.5946_5946 delT
c.5952_5953insA
c.5967_5968insA
c.6325_6326 delGT
c.6541G>T
c.6634_6637delTGTT
c.6673_6673 delA
c.6715 G>T
c.6823_6825delGAG
STOP 1909
STOP 2003
STOP 2002
STOP 2002
STOP 2109
G2181X
STOP 2227
STOP 2228
E2239X
E2275del
c.7133 C>G
c.7558 C>T
c.8234_8237delTGAC
c.8869 C>T
c.8890_8891insA
c.8915_8915delT
c.8959_8962delCTGA
c.8961_8964delGAGT
c.9097_9097delA
c.9098_9099insA
c.7617+1G>A
S2378X
R2520X
STOP 2775
Q2957X
STOP 3017
STOP 2975
STOP 2999
STOP 2999
STOP 3061
STOP 3042
34
35
36
37
38
39
40
41
42
43
44
a
Population/Country
Malay/Malaysia
Chinese/Malaysia
Chinese/Malaysia
Chinese/Malaysia
Chinese/Thailand
Indian/Malaysian
Chinese/China, Taiwan
Javanese/Indonesia
Chinese/Singapore
Chinese/Malaysia
Chinese/China
Indian/Pakistan
Chinese/China
Chinese/Malaysia
Chinese/China
Indian / Malaysia
Indian / Malaysia
Malay/Malaysia,
Philippines
Chinese/Singapore
Indian/India
Indian/India
Chinese/China
Chinese/China, Singapore,
Japan, Korea
Chinese/Malaysia, China,
Japan
Chinese/Hong Kong, China
Chinese/China
Indian/India
Malay/Malaysia
Chinese/Malaysia
Malay/Malaysia
Malay/Singapore
Chinese/Malaysia
Indian/Malaysia
Chinese/Malaysia
References
[6, 48]
BIC
BIC, [6]
[49]
[40]
BIC
[26, 50]
[51]
[30]
[6]
BIC, [26]
[31]
BIC, [26]
[45]
BIC, [26]
BIC
BIC
[45]
Chinese/Malaysia
Chinese/Malaysia
Malaysia
Indian/Malaysia
Chinese/Singapore
Chinese/Singapore
Singapore
Malaysia
Chinese/Singapore
Chinese/Malaysia
Chinese/Singapore
Novel
BIC, HUKMb
BIC; HUKM-HKL
[6]
[30]
[30]
[30]
[42]
[42]
BIC, [49] HUKM
BIC, [26, 30, 52]
[39, 53, 54]
BIC, [21, 26, 49, 52]
BIC, [42, 55]a
[42]
[6]
[6]
Novel
[30]
[6]
[6]
Novel
BIC, HUKM-HKL
[30]
[6]
[30]
Reported in Exome Sequencing Project with minor allele frequency of 0.016% in Caucasian population. None
of the other mutations were reported in Exome Sequencing Project, 1000 Genomes, or dbSNP.
b
Reported in Exome Sequencing Project with minor allele frequency of 0.0077% in Caucasian population.