Cigarette smoke induces methylation of the tumor suppressor gene NISCH

Kimberly Ostrow, Christina Michalidi, Rafael Guerrero-Preston, Mohammad Hoque, Alissa Greenberg, William Rom, David Sidransky

Research output: Contribution to journalArticle

Abstract

We have previously identified a putative tumor suppressor gene, NISCH, whose promoter is methylated in lung tumor tissue as well as in plasma obtained from lung cancer patients. NISCH was observed to be more frequently methylated in smoker lung cancer patients than in non-smoker lung cancer patients. Here, we investigated the effect of tobacco smoke exposure on methylation of the NISCH gene. We tested methylation of NISCH after oral keratinocytes were exposed to mainstream and side stream cigarette smoke extract in culture. Methylation of the promoter region of the NISCH gene was also evaluated in plasma obtained from lifetime non-smokers and light smokers (<20 pack/year), with and without lung tumors, and heavy smokers (20+ pack/year) without disease. Promoter methylation of NISCH was tested by quantitative fluorogenic real-time PCR in all samples. Promoter methylation of NISCH occurred after exposure to mainstream tobacco smoke as well as to side stream tobacco smoke in normal oral keratinocyte cell lines. NISCH methylation was also detected in 68% of high-risk, heavy smokers without detectable tumors. Interestingly, in light smokers, NISCH methylation was present in 69% of patients with lung cancer and absent in those without disease. Our pilot study indicates that tobacco smoke induces methylation changes in the NISCH gene promoter before any detectable cancer. Methylation of the NISCH gene was also found in lung cancer patients' plasma samples. After confirming these findings in longitudinally collected plasma samples from high-risk populations (such as heavy smokers), examining patients for hypermethylation of the NISCH gene may aid in identifying those who should undergo additional screening for lung cancer.

Original languageEnglish (US)
Pages (from-to)383-388
Number of pages6
JournalEpigenetics
Volume8
Issue number4
DOIs
StatePublished - 2013

Fingerprint

Tumor Suppressor Genes
Smoke
Tobacco Products
Methylation
Lung Neoplasms
Tobacco
Genes
Keratinocytes
Neoplasms
Lung
Genetic Promoter Regions
Real-Time Polymerase Chain Reaction
Cell Line
Population

Keywords

  • Lung cancer
  • Methylation
  • Nisch
  • Smoking
  • Tobacco

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Medicine(all)

Cite this

Cigarette smoke induces methylation of the tumor suppressor gene NISCH. / Ostrow, Kimberly; Michalidi, Christina; Guerrero-Preston, Rafael; Hoque, Mohammad; Greenberg, Alissa; Rom, William; Sidransky, David.

In: Epigenetics, Vol. 8, No. 4, 2013, p. 383-388.

Research output: Contribution to journalArticle

Ostrow, Kimberly ; Michalidi, Christina ; Guerrero-Preston, Rafael ; Hoque, Mohammad ; Greenberg, Alissa ; Rom, William ; Sidransky, David. / Cigarette smoke induces methylation of the tumor suppressor gene NISCH. In: Epigenetics. 2013 ; Vol. 8, No. 4. pp. 383-388.
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