Allelotyping of butadiene-induced lung and mammary adenocarcinomas of B6C3F1 mice: frequent losses of heterozygosity in regions homologous to human tumor-suppressor genes.
Allelotyping of butadiene-induced lung and mammary adenocarcinomas of B6C3F1 mice: frequent losses of heterozygosity in regions homologous to human tumor-suppressor genes.
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丁二烯诱导的 B6C3F1 小鼠肺腺癌和乳腺癌的同位素分型：与人类肿瘤抑制基因同源的区域杂合性频繁丢失。
DOI：
10.1073/pnas.91.9.3759
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发表时间：
1994
影响因子：
11.1
通讯作者：
Söderkvist,P
中科院分区：
文献类型：
--
作者：
Wiseman,RW;Cochran,C;Dietrich,W;Lander,ES;Söderkvist,P
为了确定B6C3F1小鼠肿瘤发展过程中肿瘤抑制基因失活的潜在参与，我们从丁二烯诱导的肺和乳腺腺癌的等位基因中确定了遗传损失。通过使用限制性片段和简单序列重复（或“微卫星”）中的长度多态性，对每个常染色体上的标记进行肿瘤dna中等位基因丢失的分析。在17例乳腺肿瘤中的12例和8例肺肿瘤中的2例中，在11号染色体上的肿瘤抑制基因p53 （Trp53）周围的几个位点上观察到杂合性缺失。虽然大多数这些改变似乎是由不分离引起的，但至少有两个体细胞重组或缺失的例子也被观察到。Southern分析显示，这些乳腺肿瘤之一的剩余Trp53等位基因存在纯合缺失。在17例乳腺肿瘤中的7例和1例肺肿瘤中也检测到Rb-1肿瘤抑制基因的杂合性缺失。最后，在肺肿瘤的4号染色体上观察到频繁的等位基因丢失。对9个4号染色体位点的分析确定了一个肺肿瘤中含有Ifa基因簇的间质缺失。一个肿瘤抑制基因先前在体细胞杂交研究中被定位到4号染色体的这个区域。此外，在急性淋巴细胞白血病、胶质母细胞瘤、黑色素瘤和肺癌的人类染色体9p同源区域也报道了纯合缺失。这些发现表明，肿瘤抑制基因（包括Trp53、Rb-1和4号染色体上一个未知基因）的失活在小鼠的癌变过程中起着重要作用。
To identify the potential involvement of tumor-suppressor gene inactivation during neoplastic development in B6C3F1 mice, genetic losses were determined from allelotypes of butadiene-induced lung and mammary adenocarcinomas. By using length polymorphisms in restriction fragments and simple sequence repeats, or "microsatellites," markers on each autosome were analyzed for allele losses in tumor DNAs. Losses of heterozygosity on chromosome 11 were observed at several loci surrounding the p53 tumor-suppressor gene (Trp53) in 12 of 17 mammary tumors and 2 of 8 lung tumors. Although most of these alterations appeared to result from nondisjunction, at least two examples of somatic recombination or deletion were also observed. Southern analysis revealed a homozygous deletion of the remaining Trp53 allele of one of these mammary tumors. Losses of heterozygosity were also detected at the Rb-1 tumor-suppressor gene in 7 of 17 mammary tumors and 1 lung tumor. Finally, frequent allele losses were observed on chromosome 4 in lung tumors. Analysis of nine chromosome 4 loci defined an interstitial deletion containing the Ifa gene cluster in one of the lung tumors. A tumor-suppressor gene was previously mapped to this region of chromosome 4 in studies with somatic cell hybrids. In addition, homozygous deletions have been reported in a homologous region of human chromosome 9p for acute lymphocytic leukemias, glioblastomas, melanomas, and lung carcinomas. These findings suggest that the inactivation of tumor-suppressor genes including Trp53, Rb-1, and an unidentified gene on chromosome 4 plays a significant role during carcinogenesis in mice.