title: Morphologic manifestations of gene-specific molecular alterations ("genetic addictions") in mouse models of disease.
abstract: Neoplasia in both animals and humans results in part from lasting activation of tumor-promoting genes ("oncogenes") or diminished function of genes responsible for preventing neoplastic induction ("tumor suppressor genes"). The concept of "genetic addiction" has emerged to indicate that neoplastic cells cannot maintain a malignant phenotype without sustained genotypic abnormalities related to aberrant activity of oncogene(s) and/or inactivity of tumor suppressor gene(s). Interestingly, some genetic abnormalities reliably produce distinct morphologic patterns that can be used as structural signatures indicating the presence of a specific molecular alteration. Examples of such consistent genetic/microanatomic pairings have been identified for mutated oncogenes, such as rising mucin-producing capacity with RAS overexpression, and mutated tumor suppressor genes-including PTEN eliciting cell hypertrophy, RB1 dictating neuroendocrine differentiation, and TRP53 encouraging sarcomatous transformation. Familiarity with the concept of genetic addiction, as well as the ability to recognize such regular genomic-phenotypic relationships, are of paramount importance for comparative pathologists who are engaged in phenotyping genetically engineered mice to help unravel genomic intricacies in both health and disease.
authors.affiliation: University of California–Davis, Center for Comparative Medicine, Davis, CA, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Couto
authors.forename: B
authors.initials: B
authors.lastname: Bolon
authors.forename: R D
authors.initials: RD
authors.lastname: Cardiff
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D005818:Genetic Engineering; D005838:Genotype; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D009857:Oncogenes; D010641:Phenotype