Analysis of aberrant methylation on promoter sequences of tumor suppressor genes and total DNA in sputum samples: A promising tool for early detection of COPD and lung cancer in smokers.

Leda Guzmán; María S. Depix; Ana M. Salinas; Rosa Roldán; Francisco Aguayo; Alejandra Silva; Raul Vinet

doi:10.1186/1746-1596-7-87

Analysis of aberrant methylation on promoter sequences of tumor suppressor genes and total DNA in sputum samples: A promising tool for early detection of COPD and lung cancer in smokers.

Título traducido de la contribución: Análisis de la metilación aberrante en secuencias promotoras de genes supresores de tumores y ADN total en muestras de esputo: Una herramienta prometedora para la detección temprana de la EPOC y el cáncer de pulmón en fumadores.

Leda Guzmán
, María S. Depix
, Ana M. Salinas
, Rosa Roldán
, Francisco Aguayo
, Alejandra Silva
, Raul Vinet

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

58 Citas (Scopus)

Resumen

Antecedentes: La enfermedad pulmonar obstructiva crónica (EPOC) es un trastorno asociado al humo del cigarrillo y al cáncer de pulmón (CP). Dado que los cambios epigenéticos en oncogenes y genes supresores de tumores (TSG) son claramente importantes en el desarrollo de CP. En este estudio, planteamos la hipótesis de que los fumadores de tabaco son susceptibles a la metilación en la región promotora de los TSG en las células epiteliales de las vías respiratorias en comparación con los sujetos no fumadores. El propósito de este estudio fue investigar la utilidad de la detección de la metilación del promotor de genes en muestras de esputo, como una herramienta complementaria para identificar biomarcadores de CP entre fumadores con EPOC temprana. Métodos: Determinamos la cantidad de ADN en esputo inducido de pacientes con EPOC (n = 23), CP (n = 26), así como en sujetos sanos (CTR) (n = 33), utilizando un kit comercial para la purificación de ADN, seguido de la medición de la absorbancia a 260 nm. La frecuencia de metilación de los promotores CDKN2A, CDH1 y MGMT en los mismos grupos se determinó mediante la reacción en cadena de la polimerasa (PCR) específica para la metilación. Se empleó la prueba exacta de Fisher para comparar la frecuencia de los resultados entre los diferentes grupos. Resultados: La concentración de ADN fue 7,4 y 5,8 veces mayor en pacientes con CP y EPOC que en el grupo CTR (p < 0,0001), respectivamente. El estado de metilación de CDKN2A y MGMT fue significativamente mayor en pacientes con EPOC y CP que en el grupo CTR (p < 0,0001). La frecuencia de metilación de CDH1 solo mostró una diferencia estadísticamente significativa entre los pacientes con LC y el grupo CTR (p < 0,05). Conclusiones: Proporcionamos evidencia de que la metilación aberrante de TSG en muestras de esputo inducido es una herramienta útil para el diagnóstico temprano de enfermedades pulmonares (LC y EPOC) en sujetos fumadores. Diapositivas virtuales: El resumen DEBE terminar con el siguiente texto: Diapositivas virtuales Las diapositivas virtuales de este artículo se pueden encontrar aquí: http://www.diagnosticpathology.diagnomx.eu/vs/1127865005664160

Título traducido de la contribución	Análisis de la metilación aberrante en secuencias promotoras de genes supresores de tumores y ADN total en muestras de esputo: Una herramienta prometedora para la detección temprana de la EPOC y el cáncer de pulmón en fumadores.
Idioma original	Inglés
Número de artículo	87
Publicación	Diagnostic pathology
Volumen	7
N.º	1
DOI	https://doi.org/10.1186/1746-1596-7-87
Estado	Publicada - 20 jul. 2012
Publicado de forma externa	Sí

Palabras clave

EPOC
Metilación del ADN
Cáncer de pulmón
Esputo

ODS de las Naciones Unidas

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@article{42e74ae9bf864c07a9abdc5244b19807,

title = "Analysis of aberrant methylation on promoter sequences of tumor suppressor genes and total DNA in sputum samples: A promising tool for early detection of COPD and lung cancer in smokers.",

abstract = "Background: Chronic obstructive pulmonary disease (COPD) is a disorder associated to cigarette smoke and lung cancer (LC). Since epigenetic changes in oncogenes and tumor suppressor genes (TSGs) are clearly important in the development of LC. In this study, we hypothesize that tobacco smokers are susceptible for methylation in the promoter region of TSGs in airway epithelial cells when compared with non-smoker subjects. The purpose of this study was to investigate the usefulness of detection of genes promoter methylation in sputum specimens, as a complementary tool to identify LC biomarkers among smokers with early COPD.Methods: We determined the amount of DNA in induced sputum from patients with COPD (n = 23), LC (n = 26), as well as in healthy subjects (CTR) (n = 33), using a commercial kit for DNA purification, followed by absorbance measurement at 260 nm. The frequency of CDKN2A, CDH1 and MGMT promoter methylation in the same groups was determined by methylation-specific polymerase chain reaction (MSP). The Fisher's exact test was employed to compare frequency of results between different groups.Results: DNA concentration was 7.4 and 5.8 times higher in LC and COPD compared to the (CTR) (p < 0.0001), respectively. Methylation status of CDKN2A and MGMT was significantly higher in COPD and LC patients compared with CTR group (p < 0.0001). Frequency of CDH1 methylation only showed a statistically significant difference between LC patients and CTR group (p < 0.05).Conclusions: We provide evidence that aberrant methylation of TSGs in samples of induced sputum is a useful tool for early diagnostic of lung diseases (LC and COPD) in smoker subjects.Virtual slides: The abstract MUST finish with the following text: Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1127865005664160",

keywords = "EPOC, Metilaci{\'o}n del ADN, C{\'a}ncer de pulm{\'o}n, Esputo, COPD, DNA methylation, Lung cancer, Sputum",

author = "Leda Guzm{\'a}n and Depix, \{Mar{\'i}a S.\} and Salinas, \{Ana M.\} and Rosa Rold{\'a}n and Francisco Aguayo and Alejandra Silva and Raul Vinet",

year = "2012",

month = jul,

day = "20",

doi = "10.1186/1746-1596-7-87",

language = "English",

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issn = "1746-1596",

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Analysis of aberrant methylation on promoter sequences of tumor suppressor genes and total DNA in sputum samples: A promising tool for early detection of COPD and lung cancer in smokers. / Guzmán, Leda; Depix, María S.; Salinas, Ana M. et al.
En: Diagnostic pathology, Vol. 7, N.º 1, 87, 20.07.2012.

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

TY - JOUR

T1 - Analysis of aberrant methylation on promoter sequences of tumor suppressor genes and total DNA in sputum samples

T2 - A promising tool for early detection of COPD and lung cancer in smokers.

AU - Guzmán, Leda

AU - Depix, María S.

AU - Salinas, Ana M.

AU - Roldán, Rosa

AU - Aguayo, Francisco

AU - Silva, Alejandra

AU - Vinet, Raul

PY - 2012/7/20

Y1 - 2012/7/20

N2 - Background: Chronic obstructive pulmonary disease (COPD) is a disorder associated to cigarette smoke and lung cancer (LC). Since epigenetic changes in oncogenes and tumor suppressor genes (TSGs) are clearly important in the development of LC. In this study, we hypothesize that tobacco smokers are susceptible for methylation in the promoter region of TSGs in airway epithelial cells when compared with non-smoker subjects. The purpose of this study was to investigate the usefulness of detection of genes promoter methylation in sputum specimens, as a complementary tool to identify LC biomarkers among smokers with early COPD.Methods: We determined the amount of DNA in induced sputum from patients with COPD (n = 23), LC (n = 26), as well as in healthy subjects (CTR) (n = 33), using a commercial kit for DNA purification, followed by absorbance measurement at 260 nm. The frequency of CDKN2A, CDH1 and MGMT promoter methylation in the same groups was determined by methylation-specific polymerase chain reaction (MSP). The Fisher's exact test was employed to compare frequency of results between different groups.Results: DNA concentration was 7.4 and 5.8 times higher in LC and COPD compared to the (CTR) (p < 0.0001), respectively. Methylation status of CDKN2A and MGMT was significantly higher in COPD and LC patients compared with CTR group (p < 0.0001). Frequency of CDH1 methylation only showed a statistically significant difference between LC patients and CTR group (p < 0.05).Conclusions: We provide evidence that aberrant methylation of TSGs in samples of induced sputum is a useful tool for early diagnostic of lung diseases (LC and COPD) in smoker subjects.Virtual slides: The abstract MUST finish with the following text: Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1127865005664160

AB - Background: Chronic obstructive pulmonary disease (COPD) is a disorder associated to cigarette smoke and lung cancer (LC). Since epigenetic changes in oncogenes and tumor suppressor genes (TSGs) are clearly important in the development of LC. In this study, we hypothesize that tobacco smokers are susceptible for methylation in the promoter region of TSGs in airway epithelial cells when compared with non-smoker subjects. The purpose of this study was to investigate the usefulness of detection of genes promoter methylation in sputum specimens, as a complementary tool to identify LC biomarkers among smokers with early COPD.Methods: We determined the amount of DNA in induced sputum from patients with COPD (n = 23), LC (n = 26), as well as in healthy subjects (CTR) (n = 33), using a commercial kit for DNA purification, followed by absorbance measurement at 260 nm. The frequency of CDKN2A, CDH1 and MGMT promoter methylation in the same groups was determined by methylation-specific polymerase chain reaction (MSP). The Fisher's exact test was employed to compare frequency of results between different groups.Results: DNA concentration was 7.4 and 5.8 times higher in LC and COPD compared to the (CTR) (p < 0.0001), respectively. Methylation status of CDKN2A and MGMT was significantly higher in COPD and LC patients compared with CTR group (p < 0.0001). Frequency of CDH1 methylation only showed a statistically significant difference between LC patients and CTR group (p < 0.05).Conclusions: We provide evidence that aberrant methylation of TSGs in samples of induced sputum is a useful tool for early diagnostic of lung diseases (LC and COPD) in smoker subjects.Virtual slides: The abstract MUST finish with the following text: Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1127865005664160

KW - EPOC

KW - Metilación del ADN

KW - Cáncer de pulmón

KW - Esputo

KW - COPD

KW - DNA methylation

KW - Lung cancer

KW - Sputum

UR - https://www.scopus.com/pages/publications/84865339641

U2 - 10.1186/1746-1596-7-87

DO - 10.1186/1746-1596-7-87

M3 - Article

C2 - 22818553

SN - 1746-1596

VL - 7

JO - Diagnostic pathology

JF - Diagnostic pathology

IS - 1

M1 - 87

ER -