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Measurement of Telomere Length in Colorectal Cancers for Improved Molecular Diagnosis

All tumors have in common to reactivate a telomere maintenance mechanism to allow for unlimited proliferation. On the other hand, genetic instability found in some tumors can result from the loss of telomeres. Here, we measured telomere length in colorectal cancers (CRCs) using TRF (Telomere Restric...

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Autores principales: Le Balc’h, Eric, Grandin, Nathalie, Demattei, Marie-Véronique, Guyétant, Serge, Tallet, Anne, Pagès, Jean-Christophe, Ouaissi, Mehdi, Lecomte, Thierry, Charbonneau, Michel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5618520/
https://www.ncbi.nlm.nih.gov/pubmed/28850092
http://dx.doi.org/10.3390/ijms18091871
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author Le Balc’h, Eric
Grandin, Nathalie
Demattei, Marie-Véronique
Guyétant, Serge
Tallet, Anne
Pagès, Jean-Christophe
Ouaissi, Mehdi
Lecomte, Thierry
Charbonneau, Michel
author_facet Le Balc’h, Eric
Grandin, Nathalie
Demattei, Marie-Véronique
Guyétant, Serge
Tallet, Anne
Pagès, Jean-Christophe
Ouaissi, Mehdi
Lecomte, Thierry
Charbonneau, Michel
author_sort Le Balc’h, Eric
collection PubMed
description All tumors have in common to reactivate a telomere maintenance mechanism to allow for unlimited proliferation. On the other hand, genetic instability found in some tumors can result from the loss of telomeres. Here, we measured telomere length in colorectal cancers (CRCs) using TRF (Telomere Restriction Fragment) analysis. Telomeric DNA content was also quantified as the ratio of total telomeric (TTAGGG) sequences over that of the invariable Alu sequences. In most of the 125 CRCs analyzed, there was a significant diminution in telomere length compared with that in control healthy tissue. Only 34 tumors exhibited no telomere erosion and, in some cases, a slight telomere lengthening. Telomere length did not correlate with age, gender, tumor stage, tumor localization or stage of tumor differentiation. In addition, while telomere length did not correlate with the presence of a mutation in BRAF (V-raf murine sarcoma viral oncogene homolog B), PIK3CA (phosphatidylinositol 3-kinase catalytic subunit), or MSI status, it was significantly associated with the occurrence of a mutation in KRAS. Interestingly, we found that the shorter the telomeres in healthy tissue of a patient, the larger an increase in telomere length in the tumor. Our study points to the existence of two types of CRCs based on telomere length and reveals that telomere length in healthy tissue might influence telomere maintenance mechanisms in the tumor.
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spelling pubmed-56185202017-09-30 Measurement of Telomere Length in Colorectal Cancers for Improved Molecular Diagnosis Le Balc’h, Eric Grandin, Nathalie Demattei, Marie-Véronique Guyétant, Serge Tallet, Anne Pagès, Jean-Christophe Ouaissi, Mehdi Lecomte, Thierry Charbonneau, Michel Int J Mol Sci Article All tumors have in common to reactivate a telomere maintenance mechanism to allow for unlimited proliferation. On the other hand, genetic instability found in some tumors can result from the loss of telomeres. Here, we measured telomere length in colorectal cancers (CRCs) using TRF (Telomere Restriction Fragment) analysis. Telomeric DNA content was also quantified as the ratio of total telomeric (TTAGGG) sequences over that of the invariable Alu sequences. In most of the 125 CRCs analyzed, there was a significant diminution in telomere length compared with that in control healthy tissue. Only 34 tumors exhibited no telomere erosion and, in some cases, a slight telomere lengthening. Telomere length did not correlate with age, gender, tumor stage, tumor localization or stage of tumor differentiation. In addition, while telomere length did not correlate with the presence of a mutation in BRAF (V-raf murine sarcoma viral oncogene homolog B), PIK3CA (phosphatidylinositol 3-kinase catalytic subunit), or MSI status, it was significantly associated with the occurrence of a mutation in KRAS. Interestingly, we found that the shorter the telomeres in healthy tissue of a patient, the larger an increase in telomere length in the tumor. Our study points to the existence of two types of CRCs based on telomere length and reveals that telomere length in healthy tissue might influence telomere maintenance mechanisms in the tumor. MDPI 2017-08-29 /pmc/articles/PMC5618520/ /pubmed/28850092 http://dx.doi.org/10.3390/ijms18091871 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Le Balc’h, Eric
Grandin, Nathalie
Demattei, Marie-Véronique
Guyétant, Serge
Tallet, Anne
Pagès, Jean-Christophe
Ouaissi, Mehdi
Lecomte, Thierry
Charbonneau, Michel
Measurement of Telomere Length in Colorectal Cancers for Improved Molecular Diagnosis
title Measurement of Telomere Length in Colorectal Cancers for Improved Molecular Diagnosis
title_full Measurement of Telomere Length in Colorectal Cancers for Improved Molecular Diagnosis
title_fullStr Measurement of Telomere Length in Colorectal Cancers for Improved Molecular Diagnosis
title_full_unstemmed Measurement of Telomere Length in Colorectal Cancers for Improved Molecular Diagnosis
title_short Measurement of Telomere Length in Colorectal Cancers for Improved Molecular Diagnosis
title_sort measurement of telomere length in colorectal cancers for improved molecular diagnosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5618520/
https://www.ncbi.nlm.nih.gov/pubmed/28850092
http://dx.doi.org/10.3390/ijms18091871
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