AT LEAST 4 DIFFERENT CHROMOSOMAL REGIONS ARE INVOLVED IN LOSS OF HETEROZYGOSITY IN HUMAN-BREAST CARCINOMA
AT LEAST 4 DIFFERENT CHROMOSOMAL REGIONS ARE INVOLVED IN LOSS OF HETEROZYGOSITY IN HUMAN-BREAST CARCINOMA
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DOI：
10.1016/0888-7543(89)90023-2
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发表时间：
1989-10-01
期刊：
影响因子：
4.4
通讯作者：
CORNELISSE, CJ
中科院分区：
文献类型：
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作者：
DEVILEE, P;VANDENBROEK, M;CORNELISSE, CJ
三个独立的研究小组之前曾报道，三个染色体区域，即 11p15、13q 和 17p，在人类原发性乳腺癌中被特异性降低为半合子。我们使用分散在 8 条不同染色体的 10 个臂上的 28 个多态性 DNA 标记检查了 64 个乳腺肿瘤的 DNA 杂合性丢失 (LOH)。在 5 个臂（5 条染色体）上观察到 LOH 完全或接近完全缺失。先前调用的所有三个区域的 LOH 均得到确认，最高频率出现在 17p（杂合子患者的 67%）。在 15 例信息丰富的病例中，有 7 例发现 3 号染色体（p14-p21 区域）的等位基因丢失。在 43 个显示 LOH 的肿瘤中，有 20 个肿瘤中注意到 2 至 4 个位点同时存在 LOH。等位基因丢失与所研究的六个临床组织病理学变量中的任何一个均不相关，但在我们无法证明 LOH 的一组患者中，不存在远处转移具有统计学意义（P < 0.05）。这些结果表明，一些观察到的等位基因丢失反映了随机事件，可能是遗传不稳定性的结果，但对于乳腺肿瘤特定亚类的进展并非没有生物学意义。
Three chromosome regions, i.e., 11p15, 13q, and 17p, were previously reported by three independent groups to be specifically reduced to hemizygosity in human primary breast cancer. We examined the DNA of 64 mammary tumors for loss of heterozygosity (LOH) with 28 polymorphic DNA markers dispersed on 10 arms of 8 different chromosomes. Complete or near-complete absence of LOH was observed on 5 arms (5 chromosomes). LOH at all three previously invoked regions was confirmed, and the highest frequency was found on 17p (67% of heterozygous patients). Allele loss of a marker from chromosome 3 (region p14-p21) was found in 7 of 15 informative cases. Concurrent LOH at 2 to 4 loci was noted in 20 of the 43 tumors showing LOH. Allele losses did not correlate with any of the six clinico-histopathological variables investigated, but in a group of patients in which we were unable to demonstrate LOH, the absence of distant metastases was statistically significant (P < 0.05). These results suggest that some of the observed allele losses reflect random events, possibly as a result of genetic instability, but are not without biological significance for the progression of particular subclasses of breast tumors.