Tumorigenesis is a collection of complex genetic diseases characterized by multiple defects in the homeostatic mechanisms that regulate cell growth, proliferation and differentiation.

Cancer is caused by uncontrolled proliferation and the inappropriate survival of damaged cells, which results in tumour formation. Cells have developed several safeguards to ensure that cell division, differentiation and death occur correctly and in a coordinated fashion, both during development and in the adult body.

Many regulatory factors switch on or off genes that direct cellular proliferation and differentiation. Damage to these genes, which are referred to as tumour-suppressor genes and oncogenes, is selected for in cancer.

Most tumour-suppressor genes and oncogenes are first transcribed from DNA into RNA, and are then translated into protein to exert their effects. Recent evidence indicates that small non-protein-coding RNA molecules, called microRNAs (miRNAs), might also function as tumour suppressors and oncogenes.

Mechanisms

 activation of oncogenes

• overexpression of growth factors
  • IL3 (IGH) by translocation t(5;14)(q31;q32) in B-lineage acute lymphoblastic leukemia with eosinophilia

 sequential inactivation of tumor suppressor genes

 tumoral pathways

 tumoral epigenetics

 inflammatory-mediated tumorigenesis

Types

 digestive tumorigenesis
 endocrine tumorigenesis

• neuroendocrine tumorigenesis
• thyroid tumorigenesis

 gliomagenesis (tumorigenesis of glioma)
 mammary tumorigenesis

References

 Bardelli A, Velculescu VE. Mutational analysis of gene families in human cancer. Curr Opin Genet Dev. 2005 Feb;15(1):5-12. PMID: #15661527#

 Boehm JS, Hahn WC. Understanding transformation: progress and gaps. Curr Opin Genet Dev. 2005 Feb;15(1):13-7. PMID: #15661528#

 Gregory RI, Shiekhattar R. Chromatin modifiers and carcinogenesis. Trends Cell Biol. 2004 Dec;14(12):695-702. PMID: #15564046#

 Zhao JJ, Roberts TM, Hahn WC. Functional genetics and experimental models of human cancer. Trends Mol Med. 2004 Jul;10(7):344-50. PMID: #15242683#

 Felsher DW. Reversibility of oncogene-induced cancer. Curr Opin Genet Dev. 2004 Feb;14(1):37-42. PMID: #15108803#

 Sieber OM, Heinimann K, Tomlinson IP. Genomic instability--the engine of tumorigenesis? Nat Rev Cancer. 2003 Sep;3(9):701-8. PMID: #12951589#

 Bergers G, Benjamin LE. Tumorigenesis and the angiogenic switch. Nat Rev Cancer. 2003 Jun;3(6):401-10. PMID: #12778130#

 Hahn WC, Weinberg RA. Rules for making human tumor cells. N Engl J Med. 2002 Nov 14;347(20):1593-603. PMID: #12432047#

 Manson MM. Cancer prevention -- the potential for diet to modulate molecular signalling. Trends Mol Med. 2003 Jan;9(1):11-8. PMID: #12524205#

 Wu X, Pandolfi PP. Mouse models for multistep tumorigenesis. Trends Cell Biol. 2001 Nov;11(11):S2-9. PMID: #11684435#

 Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000 Jan 7;100(1):57-70. PMID: #10647931#