A High Degree of LINE-1 Hypomethylation Is a Unique Feature of Early-Onset Colorectal Cancer
- Autores
- Antelo, Marina; Balaguer, Francesc; Shia, Jinru; Shen, Yan; Hur, Keun; Moreira, Leticia; Cuatrecasas, Miriam; Bujanda, Luis; Giraldez, Maria Dolores; Takahashi, Masanobu; Cabanne, Ana; Barugel, Mario Edmundo; Arnold, Mildred; Roca, Enrique Luis; Andreu, Montserrat; Castellvi Bel, Sergi; Llor, Xavier; Jover, Rodrigo; Castells, Antoni; Boland, C. Richard; Goel, Ajay
- Año de publicación
- 2012
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Objective: Early-onset colorectal cancer (CRC) represents a clinically distinct form of CRC that is often associated with a poor prognosis. Methylation levels of genomic repeats such as LINE-1 elements have been recognized as independent factors for increased cancer-related mortality. The methylation status of LINE-1 elements in early-onset CRC has not been analyzed previously. Design: We analyzed 343 CRC tissues and 32 normal colonic mucosa samples, including 2 independent cohorts of CRC diagnosed ≤50 years old (n = 188), a group of sporadic CRC >50 years (MSS n = 89; MSI n = 46), and a group of Lynch syndrome CRCs (n = 20). Tumor mismatch repair protein expression, microsatellite instability status, LINE-1 and MLH1 methylation, somatic BRAF V600E mutation, and germline MUTYH mutations were evaluated. Results: Mean LINE-1 methylation levels (±SD) in the five study groups were early-onset CRC, 56.6% (8.6); sporadic MSI, 67.1% (5.5); sporadic MSS, 65.1% (6.3); Lynch syndrome, 66.3% (4.5) and normal mucosa, 76.5% (1.5). Early-onset CRC had significantly lower LINE-1 methylation than any other group (p<0.0001). Compared to patients with <65% LINE-1 methylation in tumors, those with ≥65% LINE-1 methylation had significantly better overall survival (p = 0.026, log rank test). Conclusions: LINE-1 hypomethylation constitutes a potentially important feature of early-onset CRC, and suggests a distinct molecular subtype. Further studies are needed to assess the potential of LINE-1 methylation status as a prognostic biomarker for young people with CRC.
Fil: Antelo, Marina. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Balaguer, Francesc. Baylor University Medical Center; España
Fil: Shia, Jinru. Memorial Sloan Kettering Cancer Center; Estados Unidos
Fil: Shen, Yan. Universidad de Baylor; Estados Unidos
Fil: Hur, Keun. Universidad de Baylor, Dallas; Estados Unidos
Fil: Moreira, Leticia. Universidad de Barcelona; España
Fil: Cuatrecasas, Miriam. Universidad de Barcelona; España
Fil: Bujanda, Luis. Hospital Donostia; España
Fil: Giraldez, Maria Dolores. Universidad de Barcelona; España
Fil: Takahashi, Masanobu. Universidad de Bylor; Estados Unidos
Fil: Cabanne, Ana. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina
Fil: Barugel, Mario Edmundo. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina
Fil: Arnold, Mildred. Universidad de Baylor; Estados Unidos
Fil: Roca, Enrique Luis. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina
Fil: Andreu, Montserrat. Hospital Donostia; España
Fil: Castellvi Bel, Sergi. Universidad de Barcelona; España
Fil: Llor, Xavier. University of Illinois; Estados Unidos
Fil: Jover, Rodrigo. Hospital General Universitario; España
Fil: Castells, Antoni. Universidad de Barcelona; España
Fil: Boland, C. Richard. Universidad de Baylor; Estados Unidos
Fil: Goel, Ajay. Universidad de Baylor; Estados Unidos - Materia
-
HYPOMETHYLATION
EARLY-ONSET
COLORECTAL
CANCER - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/197432
Ver los metadatos del registro completo
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A High Degree of LINE-1 Hypomethylation Is a Unique Feature of Early-Onset Colorectal CancerAntelo, MarinaBalaguer, FrancescShia, JinruShen, YanHur, KeunMoreira, LeticiaCuatrecasas, MiriamBujanda, LuisGiraldez, Maria DoloresTakahashi, MasanobuCabanne, AnaBarugel, Mario EdmundoArnold, MildredRoca, Enrique LuisAndreu, MontserratCastellvi Bel, SergiLlor, XavierJover, RodrigoCastells, AntoniBoland, C. RichardGoel, AjayHYPOMETHYLATIONEARLY-ONSETCOLORECTALCANCERhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Objective: Early-onset colorectal cancer (CRC) represents a clinically distinct form of CRC that is often associated with a poor prognosis. Methylation levels of genomic repeats such as LINE-1 elements have been recognized as independent factors for increased cancer-related mortality. The methylation status of LINE-1 elements in early-onset CRC has not been analyzed previously. Design: We analyzed 343 CRC tissues and 32 normal colonic mucosa samples, including 2 independent cohorts of CRC diagnosed ≤50 years old (n = 188), a group of sporadic CRC >50 years (MSS n = 89; MSI n = 46), and a group of Lynch syndrome CRCs (n = 20). Tumor mismatch repair protein expression, microsatellite instability status, LINE-1 and MLH1 methylation, somatic BRAF V600E mutation, and germline MUTYH mutations were evaluated. Results: Mean LINE-1 methylation levels (±SD) in the five study groups were early-onset CRC, 56.6% (8.6); sporadic MSI, 67.1% (5.5); sporadic MSS, 65.1% (6.3); Lynch syndrome, 66.3% (4.5) and normal mucosa, 76.5% (1.5). Early-onset CRC had significantly lower LINE-1 methylation than any other group (p<0.0001). Compared to patients with <65% LINE-1 methylation in tumors, those with ≥65% LINE-1 methylation had significantly better overall survival (p = 0.026, log rank test). Conclusions: LINE-1 hypomethylation constitutes a potentially important feature of early-onset CRC, and suggests a distinct molecular subtype. Further studies are needed to assess the potential of LINE-1 methylation status as a prognostic biomarker for young people with CRC.Fil: Antelo, Marina. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Balaguer, Francesc. Baylor University Medical Center; EspañaFil: Shia, Jinru. Memorial Sloan Kettering Cancer Center; Estados UnidosFil: Shen, Yan. Universidad de Baylor; Estados UnidosFil: Hur, Keun. Universidad de Baylor, Dallas; Estados UnidosFil: Moreira, Leticia. Universidad de Barcelona; EspañaFil: Cuatrecasas, Miriam. Universidad de Barcelona; EspañaFil: Bujanda, Luis. Hospital Donostia; EspañaFil: Giraldez, Maria Dolores. Universidad de Barcelona; EspañaFil: Takahashi, Masanobu. Universidad de Bylor; Estados UnidosFil: Cabanne, Ana. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Barugel, Mario Edmundo. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Arnold, Mildred. Universidad de Baylor; Estados UnidosFil: Roca, Enrique Luis. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Andreu, Montserrat. Hospital Donostia; EspañaFil: Castellvi Bel, Sergi. Universidad de Barcelona; EspañaFil: Llor, Xavier. University of Illinois; Estados UnidosFil: Jover, Rodrigo. Hospital General Universitario; EspañaFil: Castells, Antoni. Universidad de Barcelona; EspañaFil: Boland, C. Richard. Universidad de Baylor; Estados UnidosFil: Goel, Ajay. Universidad de Baylor; Estados UnidosPublic Library of Science2012-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/197432Antelo, Marina; Balaguer, Francesc; Shia, Jinru; Shen, Yan; Hur, Keun; et al.; A High Degree of LINE-1 Hypomethylation Is a Unique Feature of Early-Onset Colorectal Cancer; Public Library of Science; Plos One; 7; 9; 9-2012; 1-121932-6203CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0045357info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0045357info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:06:34Zoai:ri.conicet.gov.ar:11336/197432instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:06:34.5CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
A High Degree of LINE-1 Hypomethylation Is a Unique Feature of Early-Onset Colorectal Cancer |
| title |
A High Degree of LINE-1 Hypomethylation Is a Unique Feature of Early-Onset Colorectal Cancer |
| spellingShingle |
A High Degree of LINE-1 Hypomethylation Is a Unique Feature of Early-Onset Colorectal Cancer Antelo, Marina HYPOMETHYLATION EARLY-ONSET COLORECTAL CANCER |
| title_short |
A High Degree of LINE-1 Hypomethylation Is a Unique Feature of Early-Onset Colorectal Cancer |
| title_full |
A High Degree of LINE-1 Hypomethylation Is a Unique Feature of Early-Onset Colorectal Cancer |
| title_fullStr |
A High Degree of LINE-1 Hypomethylation Is a Unique Feature of Early-Onset Colorectal Cancer |
| title_full_unstemmed |
A High Degree of LINE-1 Hypomethylation Is a Unique Feature of Early-Onset Colorectal Cancer |
| title_sort |
A High Degree of LINE-1 Hypomethylation Is a Unique Feature of Early-Onset Colorectal Cancer |
| dc.creator.none.fl_str_mv |
Antelo, Marina Balaguer, Francesc Shia, Jinru Shen, Yan Hur, Keun Moreira, Leticia Cuatrecasas, Miriam Bujanda, Luis Giraldez, Maria Dolores Takahashi, Masanobu Cabanne, Ana Barugel, Mario Edmundo Arnold, Mildred Roca, Enrique Luis Andreu, Montserrat Castellvi Bel, Sergi Llor, Xavier Jover, Rodrigo Castells, Antoni Boland, C. Richard Goel, Ajay |
| author |
Antelo, Marina |
| author_facet |
Antelo, Marina Balaguer, Francesc Shia, Jinru Shen, Yan Hur, Keun Moreira, Leticia Cuatrecasas, Miriam Bujanda, Luis Giraldez, Maria Dolores Takahashi, Masanobu Cabanne, Ana Barugel, Mario Edmundo Arnold, Mildred Roca, Enrique Luis Andreu, Montserrat Castellvi Bel, Sergi Llor, Xavier Jover, Rodrigo Castells, Antoni Boland, C. Richard Goel, Ajay |
| author_role |
author |
| author2 |
Balaguer, Francesc Shia, Jinru Shen, Yan Hur, Keun Moreira, Leticia Cuatrecasas, Miriam Bujanda, Luis Giraldez, Maria Dolores Takahashi, Masanobu Cabanne, Ana Barugel, Mario Edmundo Arnold, Mildred Roca, Enrique Luis Andreu, Montserrat Castellvi Bel, Sergi Llor, Xavier Jover, Rodrigo Castells, Antoni Boland, C. Richard Goel, Ajay |
| author2_role |
author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
HYPOMETHYLATION EARLY-ONSET COLORECTAL CANCER |
| topic |
HYPOMETHYLATION EARLY-ONSET COLORECTAL CANCER |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.2 https://purl.org/becyt/ford/3 |
| dc.description.none.fl_txt_mv |
Objective: Early-onset colorectal cancer (CRC) represents a clinically distinct form of CRC that is often associated with a poor prognosis. Methylation levels of genomic repeats such as LINE-1 elements have been recognized as independent factors for increased cancer-related mortality. The methylation status of LINE-1 elements in early-onset CRC has not been analyzed previously. Design: We analyzed 343 CRC tissues and 32 normal colonic mucosa samples, including 2 independent cohorts of CRC diagnosed ≤50 years old (n = 188), a group of sporadic CRC >50 years (MSS n = 89; MSI n = 46), and a group of Lynch syndrome CRCs (n = 20). Tumor mismatch repair protein expression, microsatellite instability status, LINE-1 and MLH1 methylation, somatic BRAF V600E mutation, and germline MUTYH mutations were evaluated. Results: Mean LINE-1 methylation levels (±SD) in the five study groups were early-onset CRC, 56.6% (8.6); sporadic MSI, 67.1% (5.5); sporadic MSS, 65.1% (6.3); Lynch syndrome, 66.3% (4.5) and normal mucosa, 76.5% (1.5). Early-onset CRC had significantly lower LINE-1 methylation than any other group (p<0.0001). Compared to patients with <65% LINE-1 methylation in tumors, those with ≥65% LINE-1 methylation had significantly better overall survival (p = 0.026, log rank test). Conclusions: LINE-1 hypomethylation constitutes a potentially important feature of early-onset CRC, and suggests a distinct molecular subtype. Further studies are needed to assess the potential of LINE-1 methylation status as a prognostic biomarker for young people with CRC. Fil: Antelo, Marina. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Balaguer, Francesc. Baylor University Medical Center; España Fil: Shia, Jinru. Memorial Sloan Kettering Cancer Center; Estados Unidos Fil: Shen, Yan. Universidad de Baylor; Estados Unidos Fil: Hur, Keun. Universidad de Baylor, Dallas; Estados Unidos Fil: Moreira, Leticia. Universidad de Barcelona; España Fil: Cuatrecasas, Miriam. Universidad de Barcelona; España Fil: Bujanda, Luis. Hospital Donostia; España Fil: Giraldez, Maria Dolores. Universidad de Barcelona; España Fil: Takahashi, Masanobu. Universidad de Bylor; Estados Unidos Fil: Cabanne, Ana. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina Fil: Barugel, Mario Edmundo. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina Fil: Arnold, Mildred. Universidad de Baylor; Estados Unidos Fil: Roca, Enrique Luis. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina Fil: Andreu, Montserrat. Hospital Donostia; España Fil: Castellvi Bel, Sergi. Universidad de Barcelona; España Fil: Llor, Xavier. University of Illinois; Estados Unidos Fil: Jover, Rodrigo. Hospital General Universitario; España Fil: Castells, Antoni. Universidad de Barcelona; España Fil: Boland, C. Richard. Universidad de Baylor; Estados Unidos Fil: Goel, Ajay. Universidad de Baylor; Estados Unidos |
| description |
Objective: Early-onset colorectal cancer (CRC) represents a clinically distinct form of CRC that is often associated with a poor prognosis. Methylation levels of genomic repeats such as LINE-1 elements have been recognized as independent factors for increased cancer-related mortality. The methylation status of LINE-1 elements in early-onset CRC has not been analyzed previously. Design: We analyzed 343 CRC tissues and 32 normal colonic mucosa samples, including 2 independent cohorts of CRC diagnosed ≤50 years old (n = 188), a group of sporadic CRC >50 years (MSS n = 89; MSI n = 46), and a group of Lynch syndrome CRCs (n = 20). Tumor mismatch repair protein expression, microsatellite instability status, LINE-1 and MLH1 methylation, somatic BRAF V600E mutation, and germline MUTYH mutations were evaluated. Results: Mean LINE-1 methylation levels (±SD) in the five study groups were early-onset CRC, 56.6% (8.6); sporadic MSI, 67.1% (5.5); sporadic MSS, 65.1% (6.3); Lynch syndrome, 66.3% (4.5) and normal mucosa, 76.5% (1.5). Early-onset CRC had significantly lower LINE-1 methylation than any other group (p<0.0001). Compared to patients with <65% LINE-1 methylation in tumors, those with ≥65% LINE-1 methylation had significantly better overall survival (p = 0.026, log rank test). Conclusions: LINE-1 hypomethylation constitutes a potentially important feature of early-onset CRC, and suggests a distinct molecular subtype. Further studies are needed to assess the potential of LINE-1 methylation status as a prognostic biomarker for young people with CRC. |
| publishDate |
2012 |
| dc.date.none.fl_str_mv |
2012-09 |
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http://hdl.handle.net/11336/197432 Antelo, Marina; Balaguer, Francesc; Shia, Jinru; Shen, Yan; Hur, Keun; et al.; A High Degree of LINE-1 Hypomethylation Is a Unique Feature of Early-Onset Colorectal Cancer; Public Library of Science; Plos One; 7; 9; 9-2012; 1-12 1932-6203 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/197432 |
| identifier_str_mv |
Antelo, Marina; Balaguer, Francesc; Shia, Jinru; Shen, Yan; Hur, Keun; et al.; A High Degree of LINE-1 Hypomethylation Is a Unique Feature of Early-Onset Colorectal Cancer; Public Library of Science; Plos One; 7; 9; 9-2012; 1-12 1932-6203 CONICET Digital CONICET |
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eng |
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dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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