Weaver Z A, McCormack S J, Liyanage M, du Manoir S, Coleman A, Schröck E, Dickson R B, Ried T
Genome Technology Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
Genes Chromosomes Cancer. 1999 Jul;25(3):251-60.
Mice carrying the MMTV-cmyc transgene develop mammary tumors at 9 to 12 months of age. Little is known about karyotypic changes in this model of human breast cancer. We have developed and applied molecular cytogenetic techniques to study chromosomal aberrations that occur in these tumors, namely, comparative genomic hybridization and spectral karyotyping. Cell lines from eight tumors were established and analyzed, four of which carried a heterozygous p53 mutation. All of the tumor cell lines revealed increases in ploidy and/or multiple numerical and structural chromosomal aberrations. No consistent differences were observed between cmyc/p53+/+ and cmyc/p53+/- tumors, suggesting that cmyc induces karyotype instability independent of p53 status. Loss of whole chromosome (Chr) 4 was detected in five of the eight tumors. Parts of Chr 4 are syntenic to human 1p31-p36, a region that is also deleted in human breast carcinomas. Four tumors carried translocations involving the distal portion of Chr 11 (syntenic to human chromosome arm 17q), including two translocations T(X;11), with cytogenetically identical breakpoints. We compare the pattern of chromosomal aberrations with human breast cancers, find similarities in several syntenic regions, and discuss the potential of an interspecies cytogenetic map of chromosomal gains and losses.
携带MMTV-cmyc转基因的小鼠在9至12个月大时会发生乳腺肿瘤。对于这种人类乳腺癌模型中的核型变化知之甚少。我们已经开发并应用分子细胞遗传学技术来研究这些肿瘤中发生的染色体畸变，即比较基因组杂交和光谱核型分析。建立并分析了来自8个肿瘤的细胞系，其中4个携带杂合型p53突变。所有肿瘤细胞系均显示出倍性增加和/或多种数量和结构染色体畸变。在cmyc/p53+/+和cmyc/p53+/-肿瘤之间未观察到一致的差异，这表明cmyc诱导核型不稳定与p53状态无关。在8个肿瘤中的5个中检测到了整条4号染色体（Chr）的缺失。4号染色体的部分区域与人类1p31-p36同线，该区域在人类乳腺癌中也会缺失。4个肿瘤携带涉及11号染色体远端部分（与人类染色体臂17q同线）的易位，包括两个T(X;11)易位，其细胞遗传学断点相同。我们将染色体畸变模式与人类乳腺癌进行比较，在几个同线区域发现了相似之处，并讨论了种间染色体增减细胞遗传图谱的潜力。
