Karyotyping serves as a comprehensive survey of genetic alterations in human cancers. The abundance of cytogenetic information in hematological malignancies and solid tumors has produced both diagnostically and prognostically relevant information, and has contributed to the positional cloning of cancer causing genes (Heim and Mitelman, 1995). However, efforts to understand the sequence of genetic aberrations during carcinogenesis and the biology of tumor progression and attempts to establish test systems for novel therapeutics depend increasingly on animal models of human cancers. Murine models of human carcinogenesis are widely used to delineate genetic mechanisms that determine tumor initiation and progression and improved methods for genetic manipulation open new avenues to study biological pathways of tumorigenesis. Karyotyping of mouse chromosomes, however, is extremely demanding because mouse chromosomes are of similar size and shape. Consequently, data on recurring chromosome aberrations in mouse models are rare. We have therefore developed molecular cytogenetic techniques that facilitate the characterization of chromosomal aberrations. The potential of CGH and SKY as genome scanning methods for detection of chromosomal aberrations in mouse metaphase spreads was explored by analyzing metaphase chromosomes from different mouse models of human carcinogenesis: (i) in chemically induced plasmacytomas in BALB/c mice, (ii) in mammary gland tumors that developed in transgenic animals that overexpress the c-myc gene under the control of the MMTV-promotor, and (iii) in thymomas that occurred in mice deficient for the ataxia telangiectasia (Atm) gene. Future research will focus on the questions whether:* the distribution of chromosomal gains and losses in mouse carcinomas is similar to the one observed in human cancers * the pattern and mechanisms of chromosomal aberrations are similar to those in human cancers, i.e., is the translocation induced activation of oncogenes important in mouse models for hematological malignancies, and do chromosomal imbalances define mouse models for human carcinomas* different induction of mouse tumors, such as the overexpression of different oncogenes, will result in specific karyotypic changes and can therefore assist in the elucidation of genetic pathways* the establishment of syntenic maps of chromosomal aberrations can be used to identify chromosomes and chromosomal regions that are important for tumorigenesis across species boundaries with increased resolution* molecular cytogenetics can contribute to the validation of mouse models of human carcinogenesis - cancer, chromosome, - Neither Human Subjects nor Human Tissues
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