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The potential utility of telomere-related markers for cancer diagnosis.

Heaphy CM, Meeker AK - J. Cell. Mol. Med. (2011)

Bottom Line: Telomeres are nucleoprotein complexes comprising the hexanucleotide DNA repeat sequence, TTAGGG and numerous telomere-associated proteins, including the six member Shelterin complex.Future directions focusing on the direct detection of dysfunctional telomeres are explored.New markers for telomere dysfunction may eventually prove clinically useful.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. cheaphy@jhmi.edu

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Related in: MedlinePlus

Model depicting the possible relationships between telomere lengths, telomerase activity and telomere dysfunction in human carcinomas. Telomere length analysis by FISH from representative examples of tumours displaying (A) extremely diminished telomere signals in cancer cells, (B) comparable telomere intensities in cancer cells and benign stromal cells, (C) extremely bright telomere signals in cancer cells compared to benign stromal cells and (D) heterogeneous cancer cell telomere lengths varying from extremely short to relatively long. For the images (original magnification ×400), the DNA is stained with DAPI (blue) and telomeric DNA is stained with a Cy3-labeled telomere-specific peptide nucleic acid probe (red). Below each panel is a proposed model depicting the telomere length distributions in each tumour and the relationship to telomere dysfunction. The critical threshold levels for telomere function for critically short and abnormally long telomeres are shown (dashed red lines). Although ∼90% of tumours display telomerase activity, the cancer cell telomere lengths may vary drastically. Thus, ongoing investigations into the cause of telomere dysfunction may unravel new molecular markers with potential translational utility.
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fig01: Model depicting the possible relationships between telomere lengths, telomerase activity and telomere dysfunction in human carcinomas. Telomere length analysis by FISH from representative examples of tumours displaying (A) extremely diminished telomere signals in cancer cells, (B) comparable telomere intensities in cancer cells and benign stromal cells, (C) extremely bright telomere signals in cancer cells compared to benign stromal cells and (D) heterogeneous cancer cell telomere lengths varying from extremely short to relatively long. For the images (original magnification ×400), the DNA is stained with DAPI (blue) and telomeric DNA is stained with a Cy3-labeled telomere-specific peptide nucleic acid probe (red). Below each panel is a proposed model depicting the telomere length distributions in each tumour and the relationship to telomere dysfunction. The critical threshold levels for telomere function for critically short and abnormally long telomeres are shown (dashed red lines). Although ∼90% of tumours display telomerase activity, the cancer cell telomere lengths may vary drastically. Thus, ongoing investigations into the cause of telomere dysfunction may unravel new molecular markers with potential translational utility.

Mentions: Although previous investigations have assessed telomere shortening in cancer cells, these length measurements have been considered a proxy for telomere dysfunction. The schematic in Figure 1 highlights the finding that the majority of tumours have telomere length alterations, either shortening or lengthening, that can eventually lead to telomere dysfunction. Although telomere length changes per se are unlikely to be useful diagnostic biomarkers, identification of the fundamental underlying molecular changes that cause telomere destabilization may unmask new markers that can aid in diagnosis of cancer.


The potential utility of telomere-related markers for cancer diagnosis.

Heaphy CM, Meeker AK - J. Cell. Mol. Med. (2011)

Model depicting the possible relationships between telomere lengths, telomerase activity and telomere dysfunction in human carcinomas. Telomere length analysis by FISH from representative examples of tumours displaying (A) extremely diminished telomere signals in cancer cells, (B) comparable telomere intensities in cancer cells and benign stromal cells, (C) extremely bright telomere signals in cancer cells compared to benign stromal cells and (D) heterogeneous cancer cell telomere lengths varying from extremely short to relatively long. For the images (original magnification ×400), the DNA is stained with DAPI (blue) and telomeric DNA is stained with a Cy3-labeled telomere-specific peptide nucleic acid probe (red). Below each panel is a proposed model depicting the telomere length distributions in each tumour and the relationship to telomere dysfunction. The critical threshold levels for telomere function for critically short and abnormally long telomeres are shown (dashed red lines). Although ∼90% of tumours display telomerase activity, the cancer cell telomere lengths may vary drastically. Thus, ongoing investigations into the cause of telomere dysfunction may unravel new molecular markers with potential translational utility.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4373325&req=5

fig01: Model depicting the possible relationships between telomere lengths, telomerase activity and telomere dysfunction in human carcinomas. Telomere length analysis by FISH from representative examples of tumours displaying (A) extremely diminished telomere signals in cancer cells, (B) comparable telomere intensities in cancer cells and benign stromal cells, (C) extremely bright telomere signals in cancer cells compared to benign stromal cells and (D) heterogeneous cancer cell telomere lengths varying from extremely short to relatively long. For the images (original magnification ×400), the DNA is stained with DAPI (blue) and telomeric DNA is stained with a Cy3-labeled telomere-specific peptide nucleic acid probe (red). Below each panel is a proposed model depicting the telomere length distributions in each tumour and the relationship to telomere dysfunction. The critical threshold levels for telomere function for critically short and abnormally long telomeres are shown (dashed red lines). Although ∼90% of tumours display telomerase activity, the cancer cell telomere lengths may vary drastically. Thus, ongoing investigations into the cause of telomere dysfunction may unravel new molecular markers with potential translational utility.
Mentions: Although previous investigations have assessed telomere shortening in cancer cells, these length measurements have been considered a proxy for telomere dysfunction. The schematic in Figure 1 highlights the finding that the majority of tumours have telomere length alterations, either shortening or lengthening, that can eventually lead to telomere dysfunction. Although telomere length changes per se are unlikely to be useful diagnostic biomarkers, identification of the fundamental underlying molecular changes that cause telomere destabilization may unmask new markers that can aid in diagnosis of cancer.

Bottom Line: Telomeres are nucleoprotein complexes comprising the hexanucleotide DNA repeat sequence, TTAGGG and numerous telomere-associated proteins, including the six member Shelterin complex.Future directions focusing on the direct detection of dysfunctional telomeres are explored.New markers for telomere dysfunction may eventually prove clinically useful.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. cheaphy@jhmi.edu

Show MeSH
Related in: MedlinePlus