RESUMEN
Objective: To analyze the mutations of BRCA1 in 9 Chinese familiar breast cancer patients. Methods: Peripheral blood samples were obtained from 9 patients enrolled from 9 breast cancer families, one normal control, 32 sporadic breast cancer patients and 33 normal donors. DNA extracted from lymphocytes was amplified by polymerase chain reaction (PCR). The 22 exons and partial introns of BRCA1 were screened by PCR denaturing high performance liquid chromatography (PCR-DHPLC) and confirmed by direct sequencing. Results: Among these 9 familiar breast cancer patients, a deleterious mutation was detected in one case in exon 11 (3870delTGTC) which was a 4 base deletion and caused a frameshift in turn. One novel and unique amino acid substitution (E867R) was detected in one case. Eight patients were detected to have a known variation in intron 18 (IVS18+65G→A), and the ratio of this variation detected was 88.9%(8/9). The ratio of this variation was 37.5%(12/32) in sporadic breast cancer patients or 33.3%(11/33) in normal control. This variation was found to be accompanied all the time with a known missense variation in exon 11 (P871L) and a polymorphism in intron 9 (IVS8 57delT). Those three variants were also detected in homozygous in one case, which implies the linkage of the 3 sites. The linkage had not been reported. Two patients had been found with a known polymorphism in exon 13 (S1436S). Another known polymorphism was found in one case (L771L). In addition, intronic variants (IVS2+48C→T, IVS2+133C→T, IVS12+112C→A) were detected. Conclusion: The mutations of BRCA1 in Chinese familiar breast cancer patients are different from the hot spots reported in Caucasian and Jewish. It is important that further study be conducted to seek for specific mutations of this gene or other possible relevant genes in Chinese familiar breast cancer patients.