DEFINITION OF A TUMOR SUPPRESSOR LOCUS WITHIN HUMAN CHROMOSOME-3P21-P22
DEFINITION OF A TUMOR SUPPRESSOR LOCUS WITHIN HUMAN CHROMOSOME-3P21-P22
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DOI：
10.1073/pnas.89.22.10877
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发表时间：
1992-11-15
影响因子：
11.1
通讯作者：
NAYLOR, SL
中科院分区：
文献类型：
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作者：
KILLARY, AM;WOLF, ME;NAYLOR, SL
涉及人类3号染色体短臂的细胞遗传学异常和高频等位基因丢失已在多种组织学不同的肿瘤中被发现。这些发现表明，一个或多个肿瘤抑制基因可能位于3p14-p25区域，尽管目前还没有明确的功能证据表明3p的特定区域参与其中。我们报告了一种快速基因检测系统，该系统可以对体内3P的特定区域进行功能分析，以抑制体内的致瘤性。构建了含有染色体3p片段的种间微细胞杂交体，并对裸鼠的致瘤性进行了筛选。获得的杂交克隆显示出显著的肿瘤抑制作用，并包含一个2兆碱基的人类染色体材料片段，该片段包含3p21区域，靠近3p22的界面。通过这些杂交克隆，我们在3p21-p22上定义了一个与肿瘤抑制密切相关的遗传位点。
Cytogenetic abnormalities and high-frequency allele losses involving the short arm of human chromosome 3 have been identified in a variety of histologically different neoplasms. These findings suggest that a tumor-suppressor gene or genes may be located in the region of 3p14-p25, although there has been no definitive functional proof for the involvement of a particular region of 3p. We report a rapid genetic assay system that has allowed functional analysis of defined regions of 3p in the suppression of tumorigenicity in vivo. Interspecific microcell hybrids containing fragments of chromosome 3p were constructed and screened for tumorigenicity in athymic nude mice. Hybrid clones were obtained that showed a dramatic tumor suppression and contained a 2-megabase fragment of human chromosomal material encompassing the region 3p21 near the interface with 3p22. With these hybrid clones, we have defined a genetic locus at 3p21-p22 intimately involved in tumor suppression.