CHFR methylation strongly correlates with methylation of DNA damage repair and apoptotic pathway genes in non-small cell lung cancer

Mingzhou Guo, Joshi Alumkal, Tatiana Drachova, Dan Gao, Serban S. Marina, Jin Jen, James G. Herman

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

DNA methylation occurs commonly in non-small cell lung cancer (NSCLC). We sought to determine the frequency and relationship of methylation of key genes involved in the pathways of mitotic checkpoint control, DNA damage repair, apoptosis, and growth factor signaling in these patients. We analyzed the DNA methylation status of eight genes (CHFR, FANCF, MGMT, p16, DAPK, ASC or TMS-1, RAR-B, and CRBP1) using nested methylation-specific PCR (MSP) on over 314 paraffin-embedded, human non-small cell lung cancer samples. We determined the methylation frequency of each gene in addition to the association of the methylation of each gene with other members of the panel. Methylation was a common event in these samples. Our methylation analysis showed frequencies of methylation of 10% for CHFR, 14% for FANCF, 30% for MGMT, 29% for p16, 17% for DAPK, 33% for ASC, 38% for RAR-B, and 7% for CRBP1. There was a strong correlation between methylation of the mitotic G2-M checkpoint gene, CHFR, and methylation of other genes in our panel involved in DNA damage repair (FANCF and MGMT) and apoptosis (DAPK and ASC) but not with other genes in our panel, including p16 (the G1-S checkpoint gene), CRBP1, or RAR-B. In addition, MGMT methylation strongly correlated with the pro-apoptotic gene, ASC. There are distinct associations of methylated genes in non-small cell lung cancer involving DNA damage repair, apoptosis, and the G2-M mitotic checkpoint control. Further studies are warranted to determine whether these methylation patterns have implications for prognosis in addition to prediction of response to chemotherapeutic agents commonly used in the treatment of non-small cell lung cancer, such as radiotherapy and platinum-or taxane-based chemotherapy.

Original languageEnglish (US)
Pages (from-to)151-158
Number of pages8
JournalDiscovery medicine
Volume19
Issue number104
StatePublished - 2015
Externally publishedYes

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Non-Small Cell Lung Carcinoma
DNA Repair
Methylation
DNA Damage
Genes
M Phase Cell Cycle Checkpoints
DNA Methylation
Apoptosis
Platinum
Gene Frequency
Paraffin
Intercellular Signaling Peptides and Proteins
Radiotherapy
Drug Therapy
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Medicine(all)

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CHFR methylation strongly correlates with methylation of DNA damage repair and apoptotic pathway genes in non-small cell lung cancer. / Guo, Mingzhou; Alumkal, Joshi; Drachova, Tatiana; Gao, Dan; Marina, Serban S.; Jen, Jin; Herman, James G.

In: Discovery medicine, Vol. 19, No. 104, 2015, p. 151-158.

Research output: Contribution to journalArticle

Guo, Mingzhou ; Alumkal, Joshi ; Drachova, Tatiana ; Gao, Dan ; Marina, Serban S. ; Jen, Jin ; Herman, James G. / CHFR methylation strongly correlates with methylation of DNA damage repair and apoptotic pathway genes in non-small cell lung cancer. In: Discovery medicine. 2015 ; Vol. 19, No. 104. pp. 151-158.
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abstract = "DNA methylation occurs commonly in non-small cell lung cancer (NSCLC). We sought to determine the frequency and relationship of methylation of key genes involved in the pathways of mitotic checkpoint control, DNA damage repair, apoptosis, and growth factor signaling in these patients. We analyzed the DNA methylation status of eight genes (CHFR, FANCF, MGMT, p16, DAPK, ASC or TMS-1, RAR-B, and CRBP1) using nested methylation-specific PCR (MSP) on over 314 paraffin-embedded, human non-small cell lung cancer samples. We determined the methylation frequency of each gene in addition to the association of the methylation of each gene with other members of the panel. Methylation was a common event in these samples. Our methylation analysis showed frequencies of methylation of 10{\%} for CHFR, 14{\%} for FANCF, 30{\%} for MGMT, 29{\%} for p16, 17{\%} for DAPK, 33{\%} for ASC, 38{\%} for RAR-B, and 7{\%} for CRBP1. There was a strong correlation between methylation of the mitotic G2-M checkpoint gene, CHFR, and methylation of other genes in our panel involved in DNA damage repair (FANCF and MGMT) and apoptosis (DAPK and ASC) but not with other genes in our panel, including p16 (the G1-S checkpoint gene), CRBP1, or RAR-B. In addition, MGMT methylation strongly correlated with the pro-apoptotic gene, ASC. There are distinct associations of methylated genes in non-small cell lung cancer involving DNA damage repair, apoptosis, and the G2-M mitotic checkpoint control. Further studies are warranted to determine whether these methylation patterns have implications for prognosis in addition to prediction of response to chemotherapeutic agents commonly used in the treatment of non-small cell lung cancer, such as radiotherapy and platinum-or taxane-based chemotherapy.",
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AU - Marina, Serban S.

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