Deletion of two separate regions on chromosome 3p in breast cancers.
Deletion of two separate regions on chromosome 3p in breast cancers.
复制标题
DOI：
--
复制
发表时间：
1994-06
期刊：
影响因子：
11.2
通讯作者：
Ling Chen;Kouji Matsumura;Guoren Deng;W. Kurisu;B. Ljung;M. Lerman;Frederick M. Waidman;Helene S. Smith
中科院分区：
文献类型：
--
作者：
Ling Chen;Kouji Matsumura;Guoren Deng;W. Kurisu;B. Ljung;M. Lerman;Frederick M. Waidman;Helene S. Smith
我们已经确定了一系列乳腺癌中染色体3p上各种位点的拷贝数。为了确定涉及的精确区域，使用一组3p13-14、3p21-22和3p24-26的RFLP探针对杂合性损失（LOH）进行了限制性内切片段长度多态性（RFLP）分析。3个位点的LOH发生率分别为41%、32%和45%。为了验证LOH数据并深入了解导致LOH的机制，我们使用3号染色体周围中心和3p区域特异性DNA探针通过荧光原位杂交（FISH）测定DNA拷贝数。在22例病例中，有15例同时出现LOH和FISH缺失，表明乳腺癌中3p处LOH的主要机制是物理缺失。22例中有2例RFLP分析显示缺失，但FISH分析未显示缺失，提示有丝分裂重组或缺失和内复制。在三个病例中，RFLP分析显示等位基因失衡，这被错误地解释为LOH，因为FISH提示一个等位基因的增加。通过构建缺失图谱，我们发现3p13-14和3p24-26两个独立的区域在一些乳腺癌中被独立缺失。此外，有4例患者在3p24-26区域有断点，1例患者在3p13区域有纯合缺失，进一步支持了在3p13-14和3p24-26区域均存在肿瘤抑制基因的假设。虽然在3p21-22区域观察到高频率的LOH，但没有直接证据支持存在与近端或远端区域的编码相反的乳腺癌肿瘤抑制基因。
We have characterized the copy number of various loci on chromosome 3p in a series of breast cancers. To determine the precise region(s) involved, restriction fragment length polymorphism (RFLP) analysis for loss of heterozygosity (LOH) was performed using a panel of RFLP probes at 3p13-14, 3p21-22, and 3p24-26. The incidence of LOH at the three loci was 41, 32, and 45%, respectively. To validate the LOH data and to gain insights into the mechanisms resulting in LOH, chromosome 3 pericentromeric and 3p region-specific DNA probes were used to determine the DNA copy number by fluorescence in situ hybridization (FISH). Among 22 cases examined, 15 showed loss by both LOH and FISH, indicating that the dominant mechanism of LOH at 3p in breast cancer is a physical deletion. Two of the 22 cases showed loss by RFLP analysis but not by FISH, suggesting either mitotic recombination or loss and endoreduplication. In three cases, RFLP analysis indicated allelic imbalance, which was incorrectly interpreted as LOH, since a gain of one allele was suggested by FISH. By constructing a deletion map, we found that 2 separate regions, 3p13-14 and 3p24-26, were independently deleted in some breast cancers. Additionally, four cases had break points within the 3p24-26 region and one case had a homozygous deletion at 3p13, further supporting the hypothesis that there are tumor suppressor genes at both 3p13-14 and 3p24-26. Although high frequency of LOH was observed at the 3p21-22 region, there was no direct evidence supporting the existence of a breast cancer tumor suppressor gene there as opposed to codeletion with either the proximal or distal region.