In addition, dicentric chromosomes (Fig. that our newly derived cancer models will be useful tools to dissect the sequential actions of genome mutations during malignant transformation, and also to identify cancer-specific genes, signaling pathways, and the role of chromosomal instability in this process. == INTRODUCTION == Human invasive carcinomas develop slowly, sometimes over decades, through stages of increasing cellular dysplasia. This process requires the acquisition of disease-specific chromosomal imbalances, which are early and recurrent events, and the gain and loss of function of oncogenes and tumor suppressor genes, respectively (Ried et al., 1999;Albertson et al., 2003). Aberrant promotor methylation patterns, increased telomerase activity, and abnormalities of the centrosomes accompany the process of malignant transformation (Kalari and Pfeifer, 2010;Artandi et al., 2000;DAssoro et al., 2002;Godinho et al., 2009). Chromosomal aneuploidy and its consequence around the genome, i.e., the acquisition of specific genomic imbalances, are defining feature of human carcinomas (Heim and Mitelman, 2009;Ried, 2009;Hanahan and Weinberg, 2011;Kolodner et al., 2011). Their conservation and the degree of recurrence are amazing. For example, the gain of chromosome arm 3q is the most common abnormality in cervical cancers, and in fact it is aconditio sine qua nonfor progression of dysplasia, which advances to premalignant cervical lesions and eventually to invasive disease (Heselmeyer et al., 1996;Heselmeyer-Haddad et al., 2005). In colorectal tumorigenesis, the gain of chromosome 7 is one of the earliest genome alterations observed hEDTP in adenomas. This is complemented by gains Haloperidol D4 of chromosome arms 8q, 13q, and 20q, and losses of 17p and 18q in invasive carcinomas (Vogelstein et al., 1988;Bardi et al., 1991;Ried et al., 1996;Postma et al., 2007;Heim and Mitelman, 2009). Human breast cancers are characterized by frequent gains of chromosome arms 1q, 8q, 16p, 17q, and 20q, and losses of 8p and 16q (Ried et al., 1995;Friedrich et al., 2009;Heim and Mitelman, 2009;Smid et al., 2011). The comprehensive evaluation of large datasets of high-resolution array comparative genomic hybridization (arrayCGH) from histologically distinct human tumors confirms these observations by solely using the distribution pattern of chromosomal gains and losses, it is possible to reproduce the classification of tumors according to their tissue of origin (Beroukhim et al., 2010). Mouse models of cancer have become valuable tools to dissect the molecular events driving tumorigenesis. With respect to hematological malignancies, such as leukemias or lymphomas, the genetic aberration profiles resemble those observed in human diseases. Mutations ofATMin humans results in ataxia telangiectasia and in mice, the homozygous deletion of this gene results in thymic lymphomas after a relatively short latency (Barlow et el., 1996). The T-cell tumors contain translocations of chromosome 14, which contains the genes for the T-cell receptor chains and ; these translocations result in abnormal rearrangements of these loci, and such rearrangements are also present Haloperidol D4 in human lymphomagenesis (Liyanage et al., 2000;Petiniot et al., 2002). Multiple transgenic mouse models have provided useful information regarding the regulation of genes associated with leukemias and lymphomas (Janz, 2006;Li et al., 2009). With respect to models of epithelial cancers, the situation is usually more complex. In a study of chemically induced murine colorectal tumors, we failed to detect genomic imbalances (Guda et al., 2004). In conrast, mouse mammary gland tumors Haloperidol D4 exhibit multiple recurrent genomic imbalances, including frequent loss of the distal bands of chromosome 4 that is homologous to human chromosome arm 1p. Additionally, these tumors have chromosomal gains that map to chromosome 15, made up of theMyconcogene (Ried et al., 2004). However, when Haloperidol D4 compared with human breast malignancy we generally observed considerably fewer copy number changes in mammary gland carcinomas that occur in transgenic mouse models. This difference may be attributable to the mode of tumor induction, which in many instances requires strong tissue-specific expression of oncogenes. Such a.