Telomere length alterations in microsatellite stable colorectal cancer and association with the immune response

Telomeres are repetitive sequences (TTAGGG) located at the end of chromosomes. Telomeres progressively shorten with each cell replication cycle, ultimately leading to chromosomal instability and loss of cell viability. Telomere length anomaly appears to be one of the earliest and most prevalent gene...

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Authors: López Dóriga Guerra, Adriana, Sanz Pamplona, Rebeca, Valle Velasco, Laura, Alonso Aguado, Maria Henar, Aussó, Susanna, Closa, Adrià, Sanjuan, Xavier, Barquero, David, Rodríguez Moranta, Francisco, Moreno Aguado, Víctor
Format: article
Status:Versión aceptada para publicación
Publication Date:2018
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/124007
Online Access:https://hdl.handle.net/2445/124007
Access Level:Open access
Keyword:Telòmer
Càncer colorectal
Telomere
Colorectal cancer
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spelling Telomere length alterations in microsatellite stable colorectal cancer and association with the immune responseLópez Dóriga Guerra, AdrianaSanz Pamplona, RebecaValle Velasco, LauraAlonso Aguado, Maria HenarAussó, SusannaClosa, AdriàSanjuan, XavierBarquero, DavidRodríguez Moranta, FranciscoMoreno Aguado, VíctorTelòmerCàncer colorectalTelomereColorectal cancerTelomeres are repetitive sequences (TTAGGG) located at the end of chromosomes. Telomeres progressively shorten with each cell replication cycle, ultimately leading to chromosomal instability and loss of cell viability. Telomere length anomaly appears to be one of the earliest and most prevalent genetic alterations in malignant transformation. Here we aim to estimate telomere length from whole-exome sequencing data in colon tumors and normal colonic mucosa, and to analyze the potential association of telomere length with clinical factors and gene expression in colon cancer. Reads containing at least five repetitions of the telomere sequence (TTAGGG) were extracted from the raw sequences of 42 adjacent normal-tumor paired samples. The number of reads from the tumor sample was normalized to build the Tumor Telomere Length Ratio (TTLR), considered an estimation of telomere length change in the tumor compared to the paired normal tissue. We evaluated the associations between TTLR and clinical factors, gene expression and copy number (CN) aberrations measured in the same tumor samples. Colon tumors showed significantly shorter telomeres than their paired normal samples. No significant association was observed between TTLR and gender, age, tumor location, prognosis, stromal infiltration or molecular subtypes. The functional gene set enrichment analysis showed pathways related to immune response significantly associated with TLLR. By extracting a relative measure of telomere length from whole-exome sequencing data, we have assessed that colon tumor cells predominantly shorten telomeres, and this alteration is associated with expression changes in genes related to immune response and inflammation in tumor cells.Elsevier201820192018info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersion28 p.application/pdfhttps://hdl.handle.net/2445/124007Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésVersió postprint del document publicat a: https://doi.org/10.1016/j.bbadis.2018.06.010Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2018, vol.1864, num. 9 (part B), p. 2992-3000https://doi.org/10.1016/j.bbadis.2018.06.010cc by-nc-nd (c) Elsevier, 2018http://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1240072026-05-29T05:05:01Z
dc.title.none.fl_str_mv Telomere length alterations in microsatellite stable colorectal cancer and association with the immune response
title Telomere length alterations in microsatellite stable colorectal cancer and association with the immune response
spellingShingle Telomere length alterations in microsatellite stable colorectal cancer and association with the immune response
López Dóriga Guerra, Adriana
Telòmer
Càncer colorectal
Telomere
Colorectal cancer
title_short Telomere length alterations in microsatellite stable colorectal cancer and association with the immune response
title_full Telomere length alterations in microsatellite stable colorectal cancer and association with the immune response
title_fullStr Telomere length alterations in microsatellite stable colorectal cancer and association with the immune response
title_full_unstemmed Telomere length alterations in microsatellite stable colorectal cancer and association with the immune response
title_sort Telomere length alterations in microsatellite stable colorectal cancer and association with the immune response
dc.creator.none.fl_str_mv López Dóriga Guerra, Adriana
Sanz Pamplona, Rebeca
Valle Velasco, Laura
Alonso Aguado, Maria Henar
Aussó, Susanna
Closa, Adrià
Sanjuan, Xavier
Barquero, David
Rodríguez Moranta, Francisco
Moreno Aguado, Víctor
author López Dóriga Guerra, Adriana
author_facet López Dóriga Guerra, Adriana
Sanz Pamplona, Rebeca
Valle Velasco, Laura
Alonso Aguado, Maria Henar
Aussó, Susanna
Closa, Adrià
Sanjuan, Xavier
Barquero, David
Rodríguez Moranta, Francisco
Moreno Aguado, Víctor
author_role author
author2 Sanz Pamplona, Rebeca
Valle Velasco, Laura
Alonso Aguado, Maria Henar
Aussó, Susanna
Closa, Adrià
Sanjuan, Xavier
Barquero, David
Rodríguez Moranta, Francisco
Moreno Aguado, Víctor
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Telòmer
Càncer colorectal
Telomere
Colorectal cancer
topic Telòmer
Càncer colorectal
Telomere
Colorectal cancer
description Telomeres are repetitive sequences (TTAGGG) located at the end of chromosomes. Telomeres progressively shorten with each cell replication cycle, ultimately leading to chromosomal instability and loss of cell viability. Telomere length anomaly appears to be one of the earliest and most prevalent genetic alterations in malignant transformation. Here we aim to estimate telomere length from whole-exome sequencing data in colon tumors and normal colonic mucosa, and to analyze the potential association of telomere length with clinical factors and gene expression in colon cancer. Reads containing at least five repetitions of the telomere sequence (TTAGGG) were extracted from the raw sequences of 42 adjacent normal-tumor paired samples. The number of reads from the tumor sample was normalized to build the Tumor Telomere Length Ratio (TTLR), considered an estimation of telomere length change in the tumor compared to the paired normal tissue. We evaluated the associations between TTLR and clinical factors, gene expression and copy number (CN) aberrations measured in the same tumor samples. Colon tumors showed significantly shorter telomeres than their paired normal samples. No significant association was observed between TTLR and gender, age, tumor location, prognosis, stromal infiltration or molecular subtypes. The functional gene set enrichment analysis showed pathways related to immune response significantly associated with TLLR. By extracting a relative measure of telomere length from whole-exome sequencing data, we have assessed that colon tumor cells predominantly shorten telomeres, and this alteration is associated with expression changes in genes related to immune response and inflammation in tumor cells.
publishDate 2018
dc.date.none.fl_str_mv 2018
2018
2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/124007
url https://hdl.handle.net/2445/124007
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1016/j.bbadis.2018.06.010
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2018, vol.1864, num. 9 (part B), p. 2992-3000
https://doi.org/10.1016/j.bbadis.2018.06.010
dc.rights.none.fl_str_mv cc by-nc-nd (c) Elsevier, 2018
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by-nc-nd (c) Elsevier, 2018
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 28 p.
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869411837944004608
score 15,812429

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