Characterization of a breast cancer cell line derived from a germ-line BRCA1 mutation carrier.
Characterization of a breast cancer cell line derived from a germ-line BRCA1 mutation carrier.
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发表时间：
1998-08
期刊：
影响因子：
11.2
通讯作者：
G. Tomlinson;T. Chen;V. Stastny;A. Virmani;M. Spillman;V. Tonk;J. Blum;N. Schneider;I. Wistuba;J. Shay;J. Minna;A. Gazdar
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作者：
G. Tomlinson;T. Chen;V. Stastny;A. Virmani;M. Spillman;V. Tonk;J. Blum;N. Schneider;I. Wistuba;J. Shay;J. Minna;A. Gazdar
一个肿瘤细胞系HCC1937是从一位24岁的BRCA1种系突变患者的原发性乳腺癌中建立的。从患者外周血淋巴细胞中建立相应的b淋巴母细胞样细胞系。BRCA1分析显示，肿瘤细胞系BRCA1 5382突变为纯合的，而患者的淋巴细胞DNA为杂合的，同样的突变，至少两个其他家庭成员的淋巴细胞DNA也是如此。肿瘤细胞系具有多种额外的遗传变化，包括高度的非整倍性，获得性TP53突变并伴有野生型等位基因丢失，获得性PTEN基因纯合缺失，以及已知与乳腺癌发病机制有关的多个位点的杂合性丢失。将原发肿瘤与细胞系进行比较，发现相同的BRCA1突变和多个位点的等位基因丢失模式相同，表明该细胞系保持了原始肿瘤的许多特性。这种乳腺肿瘤来源的细胞系可能为家族性乳腺癌发病机制的研究和阐明BRCA1的功能和定位提供一个有用的模型系统。
A tumor cell line, HCC1937, was established from a primary breast carcinoma from a 24-year-old patient with a germ-line BRCA1 mutation. A corresponding B-lymphoblastoid cell line was established from the patient's peripheral blood lymphocytes. BRCA1 analysis revealed that the tumor cell line is homozygous for the BRCA1 5382insC mutation, whereas the patient's lymphocyte DNA is heterozygous for the same mutation, as are at least two other family members' lymphocyte DNA. The tumor cell line is marked by multiple additional genetic changes including a high degree of aneuploidy, an acquired mutation of TP53 with wild-type allele loss, an acquired homozygous deletion of the PTEN gene, and loss of heterozygosity at multiple loci known to be involved in the pathogenesis of breast cancer. Comparison of the primary tumor with the cell line revealed the same BRCA1 mutation and an identical pattern of allele loss at multiple loci, indicating that the cell line had maintained many of the properties of the original tumor. This breast tumor-derived cell line may provide a useful model system for the study of familial breast cancer pathogenesis and for elucidating BRCA1 function and localization.