Lizard-Nacol S, Riedinger J M, Lizard G, Glasser A L, Coudray N, Chaplain G, Guerrin J
Laboratory of Molecular Genetics, Centre G.F. Leclerc, Dijon, France.
Int J Cancer. 1997 Aug 7;72(4):599-603. doi: 10.1002/(sici)1097-0215(19970807)72:4<599::aid-ijc8>3.0.co;2-l.
TP53 abnormalities have been reported as an early event in the process of cellular transformation of human breast cancers, and involved in mammary-tumor evolution, from in situ to invasive disease. In this study, node-negative (N-) tumors were examined for TP53 allelic loss in relation to different genetic instability events, including allelic loss at chromosome 17p13.3 and c-H-ras-1 loci, as well as alteration of the c-myc and c-erbB-2/neu oncogenes. TP53 allelic loss was analyzed to determine whether such an abnormality was the more important, among other genetic events, in the N- tumors, whether it appeared independently of these genetic events, and whether accumulation of genetic events arises in this group of breast tumors. Clinicopathological parameters were also examined. Loss of heterozygosity (LOH) at the TP53 gene appears the most frequent alteration detected (26% vs. 13%, 8%, 9% and 3% for LOH at D17S30 and c-H-ras-1 loci, and amplification of c-myc and c-erbB-2/neu respectively). There was no association between LOH at the TP53 locus and other genetic events. Among clinicopathological parameters, significant associations were observed only with estrogen-receptor-negative tumors (p = 0.05). Our results demonstrate that LOH at TP53 arises more frequently in the N- breast cancer, thus supporting earlier findings suggesting that TP53 abnormality has a role early in the pathogenesis of breast lesions. Moreover, the data indicate that accumulation of many genetic events occurs at a low level in N- breast tumors, and that TP53 abnormality occurs independently of these genetic events.
TP53异常已被报道为人类乳腺癌细胞转化过程中的早期事件，并参与了乳腺肿瘤从原位癌到浸润性疾病的演变。在本研究中，对淋巴结阴性（N-）肿瘤进行了TP53等位基因缺失检测，以研究其与不同基因不稳定事件的关系，这些事件包括染色体17p13.3和c-H-ras-1位点的等位基因缺失，以及c-myc和c-erbB-2/neu癌基因的改变。分析TP53等位基因缺失，以确定这种异常在N-肿瘤的其他基因事件中是否更为重要，它是否独立于这些基因事件出现，以及在这组乳腺肿瘤中是否会出现基因事件的累积。还检查了临床病理参数。TP53基因杂合性缺失（LOH）似乎是检测到的最常见改变（D17S30和c-H-ras-1位点的LOH分别为26%，而c-myc扩增和c-erbB-2/neu扩增分别为13%、8%、9%和3%）。TP53位点的LOH与其他基因事件之间没有关联。在临床病理参数中，仅观察到与雌激素受体阴性肿瘤有显著关联（p = 0.05）。我们的结果表明，TP53基因的LOH在N-乳腺癌中更频繁出现，从而支持了早期研究结果，即TP53异常在乳腺病变发病机制早期起作用。此外，数据表明，许多基因事件的累积在N-乳腺肿瘤中处于低水平，并且TP53异常独立于这些基因事件发生。
