Tumour-suppressor genes in prostatic oncogenesis: A positional approach
Tumour-suppressor genes in prostatic oncogenesis: A positional approach
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DOI：
10.1111/j.1464-410x.1997.tb00798.x
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发表时间：
1997-03-01
期刊：
影响因子：
--
通讯作者：
Isaacs, WB
中科院分区：
文献类型：
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作者：
Bookstein, R;Bova, GS;Isaacs, WB
遗传改变，如突变、甲基化和非整倍体，被认为是许多人类癌症的多步骤发生和进展的基础。然而，前列腺肿瘤发生中发生的遗传事件仍然相对知之甚少，尤其是在早期肿瘤中，已知癌基因或肿瘤抑制基因的突变似乎相当罕见。染色体臂7 q、8 p、10、16 q和18 q的等位基因丢失表明这些染色体上涉及新的抑制基因座;染色体臂8 p的等位基因丢失是特别频繁的，甚至在早期肿瘤中也可以检测到。我们已经使用定位方法来寻找前列腺癌中的新遗传靶点，包括染色体8 p的等位基因丢失作图和MSR基因周围染色体带8 p22的物理作图。一个纯合子体细胞缺失的前列腺淋巴结转移被映射在这个区域，跨越730-970 kb。然后详细检查该区域的表达序列。一种名为N33的新基因被发现在大多数结肠癌细胞系和一些原发性结肠直肠肿瘤中被甲基化机制沉默。其他染色体8 p22候选者的表征正在进行中。
Genetic alterations, such as mutation, methylation and aneuploidy, are thought to underlie the multistep genesis and progression of many human cancers, However, the genetic events occurring in prostatic oncogenesis are still relatively poorly understood, This is especially so in early-stage tumours, in which mutations of known oncogenes or tumour-suppressor genes appear to be quite infrequent. Allelic losses of chromosome arms 7q, 8p, 10, 16q and 18q suggest the involvement of novel suppressor loci on these chromosomes; allelic losses of chromosome arm 8p are especially frequent and may be detected even in early-stage tumours, We have used a positional approach to seek novel genetic targets in prostate cancer, including allelic-loss mapping of chromosome 8p and physical mapping of chromosome band 8p22 around the MSR gene. A homozygous somatic deletion in one prostatic nodal metastasis was mapped in this region and spanned 730-970 kb. This region was then examined in detail for expressed sequences. One novel gene, called N33, was found to be silenced by a methylation mechanism in most colon cancer cell lines and some primary colorectal tumours. Characterization of additional chromosome 8p22 candidates is in progress.