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The Armitage–Doll model is a statistical model of carcinogenesis, proposed in 1954 by Peter Armitage and Richard Doll, in which a series of discrete mutations result in cancer. [1] The original paper has recently been reprinted with a set of commentary articles.
Human isogenic disease models have been likened to 'patients in a test-tube', since they incorporate the latest research into human genetic diseases and do so without the difficulties and limitations involved in using non-human models. [2] Historically, cells obtained from animals, typically mice, have been used to model cancer-related pathways.
The central role of DNA damage and epigenetic defects in DNA repair genes in carcinogenesis. DNA damage is considered to be the primary cause of cancer. [17] More than 60,000 new naturally-occurring instances of DNA damage arise, on average, per human cell, per day, due to endogenous cellular processes (see article DNA damage (naturally occurring)).
The laboratory mouse has been instrumental in investigating the genetics of human disease, including cancer, for over 110 years. [1] The laboratory mouse has physiology and genetic characteristics very similar to humans providing powerful models for investigation of the genetic characteristics of disease.
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Under this model, cancer arises as the result of a single, isolated event, rather than the slow accumulation of multiple mutations. [4] The exact function of some tumor suppressor genes is not currently known (e.g. MEN1, WT1), [5] but based on these genes following the Knudson "two-hit" hypothesis, they are strongly presumed to be suppressor genes.
Oncogenomics is a sub-field of genomics that characterizes cancer-associated genes.It focuses on genomic, epigenomic and transcript alterations in cancer. Cancer is a genetic disease caused by accumulation of DNA mutations and epigenetic alterations leading to unrestrained cell proliferation and neoplasm formation.
The cancer stem cell model asserts that within a population of tumour cells, there is only a small subset of cells that are tumourigenic (able to form tumours). These cells are termed cancer stem cells (CSCs), and are marked by the ability to both self-renew and differentiate into non-tumourigenic progeny. The CSC model posits that the ...