Tseng S L, Yu I C, Yue C T, Chang S F, Chang T M, Wu C W, Shen C Y
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Genes Chromosomes Cancer. 1997 Dec;20(4):377-82.
Cells with abnormal TP53 lose cell cycle checkpoints, resulting in genomic instability and neoplastic transformation. However, the evidence linking the tumor-specific targets of genomic alteration to an abnormal TP53 is limited. The present study tested the hypothesis that TP53 abnormalities are correlated with an increased frequency of deletion of breast cancer susceptibility loci (17q and 13q) in breast carcinomas. Tumors from 90 patients were examined for TP53 abnormality and loss of heterozygosity (LOH) at 11 loci on 17q (17q11.2-21) and 13q (13q12-14), including the loci for BRCA1 and BRCA2. A higher frequency of LOH was consistently found at 17q or 13q loci in tumors with an abnormal TP53. The increased LOH in relation to TP53 abnormality was statistically significant at the BRCA1, D17S588, and D13S267 loci (P < 0.05) but not at the locus for BRCA2 (P = 0.64). These observations imply a possible link between an abnormal TP53 and specific genomic deletions of breast cancer susceptibility loci, which may provide clues to the role of TP53 during breast tumorigenesis.
TP53异常的细胞会失去细胞周期检查点，导致基因组不稳定和肿瘤转化。然而，将基因组改变的肿瘤特异性靶点与TP53异常联系起来的证据有限。本研究检验了以下假设：TP53异常与乳腺癌中乳腺癌易感基因座（17号染色体长臂和13号染色体长臂）缺失频率增加相关。对90例患者的肿瘤进行了TP53异常检测以及17号染色体长臂（17q11.2 - 21）和13号染色体长臂（13q12 - 14）上11个基因座的杂合性缺失（LOH）检测，包括BRCA1和BRCA2基因座。在TP53异常的肿瘤中，17号染色体长臂或13号染色体长臂基因座处始终发现更高频率的LOH。在BRCA1、D17S588和D13S267基因座，与TP53异常相关的LOH增加具有统计学意义（P < 0.05），但在BRCA2基因座无统计学意义（P = 0.64）。这些观察结果表明TP53异常与乳腺癌易感基因座的特定基因组缺失之间可能存在联系，这可能为TP53在乳腺肿瘤发生过程中的作用提供线索。
