Hypermethylation of the GATA genes in lung cancer

Mingzhou Guo, Yoshimitsu Akiyama, Michael House, Craig M. Hooker, Elizabeth Heath, Edward Gabrielson, Stephen C. Yang, Yu Han, Stephen B. Baylin, James G. Herman, Malcolm V. Brock

Research output: Contribution to journalArticle

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Abstract

Purpose: In lung cancer, DNA hypermethylation is known to be a common event. Experimental Design: Gene expression and methylation status of GATA-4, GATA-5, and GATA-6 were analyzed with cell lines and primary human lung cancers. Methylation profiles of primary lung cancers were analyzed and correlated with clinical as well as histopathological data. Results: Complete methylation was detected by methylation-specific PCR for both GATA-4 and GATA-5 in four cell lines (H358, DMS-53, A549, and H1299), all of which had no expression by reverse transcription-PCR analysis. Demethylation with 5-aza-2′deoxycytidine restored expression in each case. GATA-6 was ubiquitously expressed in all of the six cell lines. GATA-4 bisulfite sequencing revealed complete methylation of the GATA-4 promoter in H358 cells, correlating well with its lack of expression at the mRNA level. Only a few CpG sites showed methylation by bisulfite sequencing within the GATA-4 promoter in a cell line that expressed the gene. In 63 cases of primary lung cancers, GATA-4 and GATA-5 promoter methylation was detected in (42 of 63) 67% and (26 of 63) 41%, respectively. GATA-6 remained unmethylated both in cell lines and primary tumors. Six autopsy specimens of normal lung tissue showed no aberrant promoter hypermethylation for the GATA genes. Correlation of concomitant GATA-4 and GATA-5 methylation with clinicopathological parameters only found a statistically significant increase in methylation frequency with increasing patient age (P <0.001). Conclusions: These epigenetic changes in the GATA genes in lung cancer are tumor-specific, relate to the loss of GATA gene expression, and occur increasingly in the elderly.

Original languageEnglish (US)
Pages (from-to)7917-7924
Number of pages8
JournalClinical Cancer Research
Volume10
Issue number23
DOIs
StatePublished - Dec 1 2004
Externally publishedYes

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Methylation
Lung Neoplasms
Genes
Cell Line
Gene Expression
Polymerase Chain Reaction
Tumor Cell Line
Epigenomics
Reverse Transcription
Autopsy
Research Design
Lung
Messenger RNA
DNA
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Guo, M., Akiyama, Y., House, M., Hooker, C. M., Heath, E., Gabrielson, E., ... Brock, M. V. (2004). Hypermethylation of the GATA genes in lung cancer. Clinical Cancer Research, 10(23), 7917-7924. https://doi.org/10.1158/1078-0432.CCR-04-1140

Hypermethylation of the GATA genes in lung cancer. / Guo, Mingzhou; Akiyama, Yoshimitsu; House, Michael; Hooker, Craig M.; Heath, Elizabeth; Gabrielson, Edward; Yang, Stephen C.; Han, Yu; Baylin, Stephen B.; Herman, James G.; Brock, Malcolm V.

In: Clinical Cancer Research, Vol. 10, No. 23, 01.12.2004, p. 7917-7924.

Research output: Contribution to journalArticle

Guo, M, Akiyama, Y, House, M, Hooker, CM, Heath, E, Gabrielson, E, Yang, SC, Han, Y, Baylin, SB, Herman, JG & Brock, MV 2004, 'Hypermethylation of the GATA genes in lung cancer', Clinical Cancer Research, vol. 10, no. 23, pp. 7917-7924. https://doi.org/10.1158/1078-0432.CCR-04-1140
Guo M, Akiyama Y, House M, Hooker CM, Heath E, Gabrielson E et al. Hypermethylation of the GATA genes in lung cancer. Clinical Cancer Research. 2004 Dec 1;10(23):7917-7924. https://doi.org/10.1158/1078-0432.CCR-04-1140
Guo, Mingzhou ; Akiyama, Yoshimitsu ; House, Michael ; Hooker, Craig M. ; Heath, Elizabeth ; Gabrielson, Edward ; Yang, Stephen C. ; Han, Yu ; Baylin, Stephen B. ; Herman, James G. ; Brock, Malcolm V. / Hypermethylation of the GATA genes in lung cancer. In: Clinical Cancer Research. 2004 ; Vol. 10, No. 23. pp. 7917-7924.
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abstract = "Purpose: In lung cancer, DNA hypermethylation is known to be a common event. Experimental Design: Gene expression and methylation status of GATA-4, GATA-5, and GATA-6 were analyzed with cell lines and primary human lung cancers. Methylation profiles of primary lung cancers were analyzed and correlated with clinical as well as histopathological data. Results: Complete methylation was detected by methylation-specific PCR for both GATA-4 and GATA-5 in four cell lines (H358, DMS-53, A549, and H1299), all of which had no expression by reverse transcription-PCR analysis. Demethylation with 5-aza-2′deoxycytidine restored expression in each case. GATA-6 was ubiquitously expressed in all of the six cell lines. GATA-4 bisulfite sequencing revealed complete methylation of the GATA-4 promoter in H358 cells, correlating well with its lack of expression at the mRNA level. Only a few CpG sites showed methylation by bisulfite sequencing within the GATA-4 promoter in a cell line that expressed the gene. In 63 cases of primary lung cancers, GATA-4 and GATA-5 promoter methylation was detected in (42 of 63) 67{\%} and (26 of 63) 41{\%}, respectively. GATA-6 remained unmethylated both in cell lines and primary tumors. Six autopsy specimens of normal lung tissue showed no aberrant promoter hypermethylation for the GATA genes. Correlation of concomitant GATA-4 and GATA-5 methylation with clinicopathological parameters only found a statistically significant increase in methylation frequency with increasing patient age (P <0.001). Conclusions: These epigenetic changes in the GATA genes in lung cancer are tumor-specific, relate to the loss of GATA gene expression, and occur increasingly in the elderly.",
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AU - Guo, Mingzhou

AU - Akiyama, Yoshimitsu

AU - House, Michael

AU - Hooker, Craig M.

AU - Heath, Elizabeth

AU - Gabrielson, Edward

AU - Yang, Stephen C.

AU - Han, Yu

AU - Baylin, Stephen B.

AU - Herman, James G.

AU - Brock, Malcolm V.

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N2 - Purpose: In lung cancer, DNA hypermethylation is known to be a common event. Experimental Design: Gene expression and methylation status of GATA-4, GATA-5, and GATA-6 were analyzed with cell lines and primary human lung cancers. Methylation profiles of primary lung cancers were analyzed and correlated with clinical as well as histopathological data. Results: Complete methylation was detected by methylation-specific PCR for both GATA-4 and GATA-5 in four cell lines (H358, DMS-53, A549, and H1299), all of which had no expression by reverse transcription-PCR analysis. Demethylation with 5-aza-2′deoxycytidine restored expression in each case. GATA-6 was ubiquitously expressed in all of the six cell lines. GATA-4 bisulfite sequencing revealed complete methylation of the GATA-4 promoter in H358 cells, correlating well with its lack of expression at the mRNA level. Only a few CpG sites showed methylation by bisulfite sequencing within the GATA-4 promoter in a cell line that expressed the gene. In 63 cases of primary lung cancers, GATA-4 and GATA-5 promoter methylation was detected in (42 of 63) 67% and (26 of 63) 41%, respectively. GATA-6 remained unmethylated both in cell lines and primary tumors. Six autopsy specimens of normal lung tissue showed no aberrant promoter hypermethylation for the GATA genes. Correlation of concomitant GATA-4 and GATA-5 methylation with clinicopathological parameters only found a statistically significant increase in methylation frequency with increasing patient age (P <0.001). Conclusions: These epigenetic changes in the GATA genes in lung cancer are tumor-specific, relate to the loss of GATA gene expression, and occur increasingly in the elderly.

AB - Purpose: In lung cancer, DNA hypermethylation is known to be a common event. Experimental Design: Gene expression and methylation status of GATA-4, GATA-5, and GATA-6 were analyzed with cell lines and primary human lung cancers. Methylation profiles of primary lung cancers were analyzed and correlated with clinical as well as histopathological data. Results: Complete methylation was detected by methylation-specific PCR for both GATA-4 and GATA-5 in four cell lines (H358, DMS-53, A549, and H1299), all of which had no expression by reverse transcription-PCR analysis. Demethylation with 5-aza-2′deoxycytidine restored expression in each case. GATA-6 was ubiquitously expressed in all of the six cell lines. GATA-4 bisulfite sequencing revealed complete methylation of the GATA-4 promoter in H358 cells, correlating well with its lack of expression at the mRNA level. Only a few CpG sites showed methylation by bisulfite sequencing within the GATA-4 promoter in a cell line that expressed the gene. In 63 cases of primary lung cancers, GATA-4 and GATA-5 promoter methylation was detected in (42 of 63) 67% and (26 of 63) 41%, respectively. GATA-6 remained unmethylated both in cell lines and primary tumors. Six autopsy specimens of normal lung tissue showed no aberrant promoter hypermethylation for the GATA genes. Correlation of concomitant GATA-4 and GATA-5 methylation with clinicopathological parameters only found a statistically significant increase in methylation frequency with increasing patient age (P <0.001). Conclusions: These epigenetic changes in the GATA genes in lung cancer are tumor-specific, relate to the loss of GATA gene expression, and occur increasingly in the elderly.

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