Tomlinson G E, Chen T T, Stastny V A, Virmani A K, Spillman M A, Tonk V, Blum J L, Schneider N R, Wistuba I I, Shay J W, Minna J D, Gazdar A F
Department of Pediatrics, and the Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas 75235-8593, USA.
Cancer Res. 1998 Aug 1;58(15):3237-42.
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.
一种肿瘤细胞系HCC1937是从一名患有胚系BRCA1突变的24岁原发性乳腺癌患者的肿瘤中建立的。从该患者的外周血淋巴细胞中建立了相应的B淋巴母细胞系。BRCA1分析显示，该肿瘤细胞系对于BRCA1 5382insC突变是纯合的，而患者的淋巴细胞DNA对于相同突变是杂合的，至少另外两名家庭成员的淋巴细胞DNA也是如此。该肿瘤细胞系具有多个其他遗传改变，包括高度非整倍体、TP53获得性突变伴野生型等位基因缺失、PTEN基因获得性纯合缺失以及多个已知参与乳腺癌发病机制的位点杂合性缺失。原发性肿瘤与细胞系的比较显示相同的BRCA1突变以及多个位点相同的等位基因缺失模式，表明该细胞系保留了原始肿瘤的许多特性。这种源自乳腺肿瘤的细胞系可能为研究家族性乳腺癌发病机制以及阐明BRCA1功能和定位提供一个有用的模型系统。
