LOSS OF HETEROZYGOSITY ON THE SHORT ARM OF CHROMOSOME-17 IS ASSOCIATED WITH HIGH PROLIFERATIVE CAPACITY AND DNA ANEUPLOIDY IN PRIMARY HUMAN BREAST-CANCER
LOSS OF HETEROZYGOSITY ON THE SHORT ARM OF CHROMOSOME-17 IS ASSOCIATED WITH HIGH PROLIFERATIVE CAPACITY AND DNA ANEUPLOIDY IN PRIMARY HUMAN BREAST-CANCER
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DOI：
10.1073/pnas.88.9.3847
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发表时间：
1991-05-01
影响因子：
11.1
通讯作者：
SMITH, HS
中科院分区：
文献类型：
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作者：
CHEN, LC;NEUBAUER, A;SMITH, HS
在52例未经治疗的原发性乳腺癌中，27例（52%）发现17号染色体短臂（17 p）的杂合性丢失（洛）。 这种17 p等位基因丢失与与侵袭性肿瘤行为相关的两个参数之间存在显着相关性：高细胞增殖分数和DNA非整倍体。 在其他9个染色体位点的洛的肿瘤中未发现这些与高细胞增殖分数和DNA非整倍体的相关性。 p53基因是一个假定的肿瘤抑制基因，位于17 p13，检测其畸变以确定其是否是乳腺癌中17 p洛的靶基因。 与其他类型的人类癌症不同，p53基因没有纯合缺失或重排，13例中只有2例（15%）在先前定位突变“热点”的保守区域发生突变。 因此，我们推测，在乳腺癌中，染色体17 p上除p53基因以外的基因的丢失或失活或p53基因失活的不同机制可能是导致观察到的高标记指数和与17 p处洛相关的DNA非整倍体的原因。
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.