[BRCA1 1100delAT is a recurrent mutation in Chinese women with familial breast cancer].
OBJECTIVE
Previous investigation on BRCA1 gene mutations in thirty-five breast cancer patients with affected relatives in Shanghai identified four germ-line mutations (1100delAT, IVS17-1G > T, IVS21+1G > C and 5640delA). To our knowledge, up to now, no founder mutation in BRCA1 gene has been identified in Chinese mainland population. The aim of this study was to investigate whether there are recurrent mutations or 'founder mutations' in Chinese mainland population.


METHODS
Peripheral blood samples were collected from 60 breast cancer patients with at least one first-degree relative affected with breast cancer from Shanghai, Jinan, Qingdao, and Shenyang. DNA extracted from lymphocytes was amplified by polymerase chain reaction (PCR) to analyze the 4 germ-line mutations (1100delAT, IVS17-1G > T, IVS21+1G > C and 5640delA) discovered previously: the amplicons were analyzed by denaturing high-performance liquid chromatography (DHPLC), and those with abnormal chromatographic profiles were confirmed by direct sequencing. Four BRCA1-linked markers were used to do allelotype analysis.


RESULTS
Only the 1100delAT mutation in BRCA1 gene recurred in two unrelated individuals. Allelotype analysis showed that the two individuals who carried the 1100delAT mutation shared the same allelotype at 4 sites: D17S855, D17S1322, D17S1326, and D17S1327, which was different from the allelotype of the patients who carried the mutation at the site D17S1322 previously reported in Shanghai population. This recurrent mutation gave an overall prevalence of 3.16% (3/95) in all of our investigated population. A novel mutation, 5589del8, was found in one case.


CONCLUSIONS
Recurrent mutation is found in Chinese mainland familial breast cancer patients for the first time. 1100delAT mutation may be a hotspot in BRCA1 gene in Chinese population. Whether this mutation is a founder mutation in the Northern Chinese community need further investigation.
Li
Wen-Feng
WF
Breast Cancer Institute, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Hu
Zhen
Z
Zhang
Bin
B
Cao
Ming-Zhi
MZ
Wang
Yong-Sheng
YS
Liu
Xiao-Yi
XY
Zhao
Lin
L
Liu
Yan-Bing
YB
Yuan
Wen-Tao
WT
Shen
Zhen-Zhou
ZZ
Huang
Wei
W
Shao
Zhi-Min
ZM
D000328:Adult; D000368:Aged; D000483:Alleles; D019313:BRCA1 Protein / Q000235:genetics*; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D002681:China; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion
D019313:BRCA1 Protein