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Toward a molecular classification of colorectal cancer: the role of telomere length.

Baichoo E, Boardman LA - Front Oncol (2014)

Bottom Line: Telomere length changes also appear to impact disease burden, progression, and overall survival.This review covers contemporary views on telomere biology and CRC risk, with a brief overview of analytical methods employed in telomere measurement.We conclude with arguments in favor of including telomere assessment in the molecular profiling of CRCs.

View Article: PubMed Central - PubMed

Affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic , Rochester, MN , USA.

ABSTRACT
Telomere biology is central to the maintenance of genomic stability and telomeric dysfunction is thought to be an early stage in carcinogenesis. Reports of telomere lengths and their ascribed colorectal cancer (CRC) risks have been discordant, with both very short and very long telomeres implicated. Nevertheless, telomeres appear to play a very central role in cancer initiation. Telomere length changes also appear to impact disease burden, progression, and overall survival. This review covers contemporary views on telomere biology and CRC risk, with a brief overview of analytical methods employed in telomere measurement. We conclude with arguments in favor of including telomere assessment in the molecular profiling of CRCs.

No MeSH data available.


Related in: MedlinePlus

Telomere length and its relationship to cell division, senescence, and senescence by-pass.
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Figure 1: Telomere length and its relationship to cell division, senescence, and senescence by-pass.

Mentions: Telomere length changes have been linked to numerous cancers, including colorectal cancer (CRC). Results from studies analyzing telomere lengths in CRC have been discordant, presenting evidence that both ends of the spectrum (shorter and longer lengths) have a possible role in CRC occurrence (1–3). Moreover, reports of association have been described (1, 4, 5). Nevertheless, studies linking telomere attrition, or shortening, to an increase in CRC risk have classically dominated literature. Telomeric dysfunction is thought to represent an early step in many epithelial cancers (6). As telomeres reach their critical length, senescent signals are sent, and cells undergo cellular arrest and apoptosis. By-passing this senescent signal and cellular arrest results in continuous replication, with progressive telomere shortening. Eventually telomeres become so short that end-to-end fusions with structural and numerical chromosomal changes, anaphase bridging, and subsequent chromosomal instability ensue (7). This so-called telomere catastrophe halts further cellular divisions (8). However, in the presence of loss of tumor suppressor function, such as an APC mutation or p53 inactivation, pre-malignant cells are able to by-pass this event through telomere maintenance mechanisms. Telomerase, a ribonucleoprotein reverse transcriptase, stabilizes the telomere lengths, protecting the altered chromosomes, and immortalizing pre-malignant cells, thus enabling cancer progression (9, 10). This telomerase upregulation occurs at the critical point in the adenoma-carcinoma transition, allowing evasion of telomeric catastrophe, and supporting malignant progression (see Figure 1) (3, 11). Less-commonly, telomere length may be preserved through a recombination-dependent mechanism (12).


Toward a molecular classification of colorectal cancer: the role of telomere length.

Baichoo E, Boardman LA - Front Oncol (2014)

Telomere length and its relationship to cell division, senescence, and senescence by-pass.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061573&req=5

Figure 1: Telomere length and its relationship to cell division, senescence, and senescence by-pass.
Mentions: Telomere length changes have been linked to numerous cancers, including colorectal cancer (CRC). Results from studies analyzing telomere lengths in CRC have been discordant, presenting evidence that both ends of the spectrum (shorter and longer lengths) have a possible role in CRC occurrence (1–3). Moreover, reports of association have been described (1, 4, 5). Nevertheless, studies linking telomere attrition, or shortening, to an increase in CRC risk have classically dominated literature. Telomeric dysfunction is thought to represent an early step in many epithelial cancers (6). As telomeres reach their critical length, senescent signals are sent, and cells undergo cellular arrest and apoptosis. By-passing this senescent signal and cellular arrest results in continuous replication, with progressive telomere shortening. Eventually telomeres become so short that end-to-end fusions with structural and numerical chromosomal changes, anaphase bridging, and subsequent chromosomal instability ensue (7). This so-called telomere catastrophe halts further cellular divisions (8). However, in the presence of loss of tumor suppressor function, such as an APC mutation or p53 inactivation, pre-malignant cells are able to by-pass this event through telomere maintenance mechanisms. Telomerase, a ribonucleoprotein reverse transcriptase, stabilizes the telomere lengths, protecting the altered chromosomes, and immortalizing pre-malignant cells, thus enabling cancer progression (9, 10). This telomerase upregulation occurs at the critical point in the adenoma-carcinoma transition, allowing evasion of telomeric catastrophe, and supporting malignant progression (see Figure 1) (3, 11). Less-commonly, telomere length may be preserved through a recombination-dependent mechanism (12).

Bottom Line: Telomere length changes also appear to impact disease burden, progression, and overall survival.This review covers contemporary views on telomere biology and CRC risk, with a brief overview of analytical methods employed in telomere measurement.We conclude with arguments in favor of including telomere assessment in the molecular profiling of CRCs.

View Article: PubMed Central - PubMed

Affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic , Rochester, MN , USA.

ABSTRACT
Telomere biology is central to the maintenance of genomic stability and telomeric dysfunction is thought to be an early stage in carcinogenesis. Reports of telomere lengths and their ascribed colorectal cancer (CRC) risks have been discordant, with both very short and very long telomeres implicated. Nevertheless, telomeres appear to play a very central role in cancer initiation. Telomere length changes also appear to impact disease burden, progression, and overall survival. This review covers contemporary views on telomere biology and CRC risk, with a brief overview of analytical methods employed in telomere measurement. We conclude with arguments in favor of including telomere assessment in the molecular profiling of CRCs.

No MeSH data available.


Related in: MedlinePlus