Chen L C, Neubauer A, Kurisu W, Waldman F M, Ljung B M, Goodson W, Goldman E S, Moore D, Balazs M, Liu E
Geraldine Brush Cancer Research Institute at Pacific Presbyterian Medical Center, San Francisco, CA 94115.
Proc Natl Acad Sci U S A. 1991 May 1;88(9):3847-51. doi: 10.1073/pnas.88.9.3847.
Loss of heterozygosity (LOH) on the short arm of chromosome 17 (17p) was found in 27 of 52 (52%) previously untreated primary breast cancers. There was a significant correlation between this 17p allelic loss and two parameters associated with aggressive tumor behavior: high cellular proliferative fraction and DNA aneuploidy. These correlations with high cellular proliferative fraction and DNA aneuploidy were not found in tumors with LOH at nine other chromosome locations. The p53 gene, a putative tumor suppressor gene located at 17p13, was examined for aberrations to determine whether it is the target for the 17p LOH in breast cancer. Unlike other types of human cancer, there were no homozygous deletions or rearrangements of the p53 gene, and only 2 of 13 (15%) were mutated in the conserved region where mutational "hot spots" have been previously located. Therefore, we hypothesize that, in breast cancer, either loss or inactivation of gene(s) on chromosome 17p other than the p53 gene or a different mechanism of p53 gene inactivation may be responsible for the observed high labeling index and DNA aneuploidy associated with LOH at 17p.
在52例未经治疗的原发性乳腺癌中，有27例（52%）发现17号染色体短臂（17p）杂合性缺失（LOH）。这种17p等位基因缺失与两个与侵袭性肿瘤行为相关的参数之间存在显著相关性：高细胞增殖分数和DNA非整倍体。在其他九个染色体位置发生LOH的肿瘤中，未发现与高细胞增殖分数和DNA非整倍体的这些相关性。位于17p13的假定肿瘤抑制基因p53基因，检测其畸变以确定它是否是乳腺癌中17p LOH的靶点。与其他类型的人类癌症不同，p53基因没有纯合缺失或重排，在先前已定位突变“热点”的保守区域中，13例中只有2例（15%）发生突变。因此，我们推测，在乳腺癌中，除p53基因外，17p染色体上其他基因的缺失或失活，或p53基因失活的不同机制，可能是观察到的与17p LOH相关的高标记指数和DNA非整倍体的原因。
