Zhou Yuan-zheng, Sun Qiang, Lin Shou-qing, Wang Jian, Liu Bin, Li Jing-xiang, Zhou Yi-dong, Ye Jing, Han Hua, Fang Fu-de
Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Beijing 100730, China.
Zhonghua Yi Xue Za Zhi. 2004 Feb 17;84(4):294-8.
To detect BRCA1 and BRCA2 gene germline mutation in the Chinese breast cancer families.
Samples of peripheral blood were collected to prepare genomic DNA by conventional techniques from 15 inherited breast cancer patients from 14 breast cancer families, 76 sporadic breast cancer patients, and 100 healthy controls based on informed consent. Exons 4, 8, 11 and 18 - 20 of BRCA1, and exons 1 - 14, 17 - 24 and 27 of BRCA2, were analyzed using DNA direct sequencing.
Six single nucleotide polymorphisms (SNPs) were found on the exon 11 of BRCA1, 2 being silent changes without change of amino acid coding, and 4 with change of amino acid coding among which 2 were polymorphic amino acid alterations and 2 were pathogenic SNPs, i.e. mutational sites. One novel BRCA1 mutation, C1196T (Pro 359 Leu), was identified in a family breast cancer patients, who was diagnosed at the age of 37. Another BRCA1 mutation, Trp 372 stop was found in a breast cancer patient who was diagnosed at the age 29. Eight SNPs were found on the exon3, 10 and 11 of BRCA2, among which 5 were silent changes and 3 were polymorphic amino acid alterations. A1093C (Asn289His) in exon 10 and A 3199G (Asn991Asp) in exon 11 being found simultaneously in the patients of 2 families but not appearing in pool DNA sample, and Asn 371 His appearing as A/C heterozygote in pool DNA sample.
Two pathogenic SNPs have been found in BRCA1 and may be related to early-onset breast cancer. One of them may be a novel mutation characterized of familial breast cancer in China.
检测中国乳腺癌家系中BRCA1和BRCA2基因的种系突变。
在获得知情同意后，采集14个乳腺癌家系的15例遗传性乳腺癌患者、76例散发性乳腺癌患者及100例健康对照者的外周血样本，采用常规技术制备基因组DNA。运用DNA直接测序法分析BRCA1基因的第4、8、11外显子以及第18 - 20外显子，BRCA2基因的第1 - 14、17 - 24及27外显子。
在BRCA1基因的第11外显子上发现6个单核苷酸多态性（SNP），其中2个为同义突变，不改变氨基酸编码，4个改变氨基酸编码，其中2个为多态性氨基酸改变，2个为致病性SNP，即突变位点。在1例37岁被诊断为乳腺癌的家系患者中鉴定出1个新的BRCA1突变，C1196T（Pro 359 Leu）。在1例29岁被诊断为乳腺癌的患者中发现另1个BRCA1突变，Trp 372 stop。在BRCA2基因的第3、10和11外显子上发现8个SNP，其中5个为同义突变，3个为多态性氨基酸改变。在2个家系的患者中同时发现第10外显子的A1093C（Asn289His）和第11外显子的A 3199G（Asn991Asp），但在混合DNA样本中未出现，Asn 371 His在混合DNA样本中表现为A/C杂合子。
在BRCA1基因中发现2个致病性SNP，可能与早发性乳腺癌相关。其中1个可能是中国家族性乳腺癌的新突变。
