Morphologic manifestations of gene-specific molecular alterations ("genetic addictions") in mouse models of disease

S. S. Couto, B. Bolon, Robert Cardiff

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)116-129
Number of pages14
JournalVeterinary Pathology
Volume49
Issue number1
DOIs
StatePublished - Jan 1 2012

Fingerprint

Tumor Suppressor Genes
Oncogenes
Genetic Phenomena
tumor suppressor genes
Molecular Biology
oncogenes
animal models
Genes
Aptitude
genes
Mucins
genomics
phenotype
Hypertrophy
neoplasms
mucins
Neoplasms
hypertrophy
Phenotype
Health

Keywords

  • genetic addiction
  • genetically engineered mouse model
  • oncogene addiction
  • pathway pathology
  • phenotype
  • Pten
  • Ras
  • Rb
  • Trp53

ASJC Scopus subject areas

  • veterinary(all)

Cite this

Morphologic manifestations of gene-specific molecular alterations ("genetic addictions") in mouse models of disease. / Couto, S. S.; Bolon, B.; Cardiff, Robert.

In: Veterinary Pathology, Vol. 49, No. 1, 01.01.2012, p. 116-129.

Research output: Contribution to journalArticle

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