telomere shortening

Telomeres, nucleoprotein complexes at chromosome ends, protect chromosomes against end-to-end fusion.

In vitro studies in human fibroblast models indicated that telomere dysfunction results in chromosome instability.

Loss of telomere function can result either from critical shortening of telomeric DNA or from loss of distinct telomere-capping proteins.

It is less clear whether telomere dysfunction has an important role in human cancer development in vivo.

Several chromosomal aberrations that theoretically could result from telomere dysfunction (terminal deletions, gains/losses of chromosome parts, nonreciprocal translocations), or aberrations that are unlikely to result from telomere dysfunction (e.g., reciprocal translocations or inversions).

Tumors

 acute myeloid leukemia (AML) (16281260)

• AML with multiple chromosome aberrations that could theoretically result from telomere dysfunction is invariably characterized by critically short telomeres. (16281260)
• Short telomeres in this group are not associated with low telomerase activity or decreased expression of essential telomeric capping proteins TRF2 and POT1. (16281260)
  In contrast, telomerase activity levels are significantly higher in AML with short telomeres. (16281260)
• Notably, short telomeres in the presence of high telomerase may relate to significantly higher expression of TRF1, a negative regulator of telomere length. (16281260)
• Age-related critical telomere shortening may have a role in generating chromosome instability in human AML development. (16281260)

See also

 chromosome instability
 cancer development

References

 Swiggers SJ, Kuijpers MA, de Cort MJ, Beverloo HB, Zijlmans JM. Critically short telomeres in acute myeloid leukemia with loss or gain of parts of chromosomes. Genes Chromosomes Cancer. 2006 Mar;45(3):247-56. PMID: 16281260

Reviews

 Lustig AJ. Clues to catastrophic telomere loss in mammals from yeast telomere rapid deletion. Nat Rev Genet. 2003 Nov;4(11):916-23. PMID: 14634639

 Artandi SE. Telomere shortening and cell fates in mouse models of neoplasia. Trends Mol Med. 2002 Jan;8(1):44-7. PMID: 11796266