5′ CpG island methylation of the FHIT gene is correlated with loss of gene expression in lung and breast cancer

S. Zöchbauer-Müller, K. M. Fong, A. Maitra, S. Lam, J. Geradts, R. Ashfaq, A. K. Virmani, S. Milchgrub, A. F. Gazdar, J. D. Minna

Research output: Contribution to journalArticle

Abstract

Allele loss and loss of expression of fragile histidine triad (FHIT), a putative tumor suppressor gene located in chromosome region 3p14.2, are frequent in several types of cancers. Tumor-acquired methylation of promoter region CpG islands is one method for silencing tumor suppressor genes. We investigated 5′ CpG island methylation of the FHIT gene in 107 primary non-small cell lung cancer (NSCLC) samples and corresponding nonmalignant lung tissues, 39 primary breast carcinomas, as well as in 49 lung and 22 breast cancer cell lines by a methylation-specific PCR assay. In addition, we analyzed brushes from the bronchial epithelium of 35 heavy smokers without cancer. FHIT methylation was detected in 37% of primary NSCLCs, 31% of primary breast cancers, and 65% of lung and 86% of breast cancer cell lines. The frequency of methylation in small cell and NSCLC cell lines were identical. Methylation was found in 9% of the corresponding nonmalignant lung tissues and in 17% of bronchial brushes from heavy cigarette smokers. FHIT methylation was significantly correlated with loss of FHIT mRNA expression by Northern blot analysis in lung cancer cell lines and with loss of Fhit expression in NSCLC and breast tumors by immunostaining. We conclude that methylation of FHIT is a frequent event in NSCLC and breast cancers and is an important mechanism for loss of expression of this gene. Methylation of FHIT commences during lung cancer pathogenesis and may represent a marker for risk assessment.

Original languageEnglish (US)
Pages (from-to)3581-3585
Number of pages5
JournalCancer Research
Volume61
Issue number9
StatePublished - May 1 2001
Externally publishedYes

Fingerprint

CpG Islands
Histidine
Methylation
Lung Neoplasms
Breast Neoplasms
Gene Expression
Genes
Non-Small Cell Lung Carcinoma
Cell Line
Tumor Suppressor Genes
Lung
Neoplasms
Genetic Promoter Regions
Tobacco Products
Northern Blotting
Epithelium
Chromosomes
Alleles
Polymerase Chain Reaction
Messenger RNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Zöchbauer-Müller, S., Fong, K. M., Maitra, A., Lam, S., Geradts, J., Ashfaq, R., ... Minna, J. D. (2001). 5′ CpG island methylation of the FHIT gene is correlated with loss of gene expression in lung and breast cancer. Cancer Research, 61(9), 3581-3585.

5′ CpG island methylation of the FHIT gene is correlated with loss of gene expression in lung and breast cancer. / Zöchbauer-Müller, S.; Fong, K. M.; Maitra, A.; Lam, S.; Geradts, J.; Ashfaq, R.; Virmani, A. K.; Milchgrub, S.; Gazdar, A. F.; Minna, J. D.

In: Cancer Research, Vol. 61, No. 9, 01.05.2001, p. 3581-3585.

Research output: Contribution to journalArticle

Zöchbauer-Müller, S, Fong, KM, Maitra, A, Lam, S, Geradts, J, Ashfaq, R, Virmani, AK, Milchgrub, S, Gazdar, AF & Minna, JD 2001, '5′ CpG island methylation of the FHIT gene is correlated with loss of gene expression in lung and breast cancer', Cancer Research, vol. 61, no. 9, pp. 3581-3585.
Zöchbauer-Müller S, Fong KM, Maitra A, Lam S, Geradts J, Ashfaq R et al. 5′ CpG island methylation of the FHIT gene is correlated with loss of gene expression in lung and breast cancer. Cancer Research. 2001 May 1;61(9):3581-3585.
Zöchbauer-Müller, S. ; Fong, K. M. ; Maitra, A. ; Lam, S. ; Geradts, J. ; Ashfaq, R. ; Virmani, A. K. ; Milchgrub, S. ; Gazdar, A. F. ; Minna, J. D. / 5′ CpG island methylation of the FHIT gene is correlated with loss of gene expression in lung and breast cancer. In: Cancer Research. 2001 ; Vol. 61, No. 9. pp. 3581-3585.
@article{e788f46fa16a4d0c9722c337bd192843,
title = "5′ CpG island methylation of the FHIT gene is correlated with loss of gene expression in lung and breast cancer",
abstract = "Allele loss and loss of expression of fragile histidine triad (FHIT), a putative tumor suppressor gene located in chromosome region 3p14.2, are frequent in several types of cancers. Tumor-acquired methylation of promoter region CpG islands is one method for silencing tumor suppressor genes. We investigated 5′ CpG island methylation of the FHIT gene in 107 primary non-small cell lung cancer (NSCLC) samples and corresponding nonmalignant lung tissues, 39 primary breast carcinomas, as well as in 49 lung and 22 breast cancer cell lines by a methylation-specific PCR assay. In addition, we analyzed brushes from the bronchial epithelium of 35 heavy smokers without cancer. FHIT methylation was detected in 37{\%} of primary NSCLCs, 31{\%} of primary breast cancers, and 65{\%} of lung and 86{\%} of breast cancer cell lines. The frequency of methylation in small cell and NSCLC cell lines were identical. Methylation was found in 9{\%} of the corresponding nonmalignant lung tissues and in 17{\%} of bronchial brushes from heavy cigarette smokers. FHIT methylation was significantly correlated with loss of FHIT mRNA expression by Northern blot analysis in lung cancer cell lines and with loss of Fhit expression in NSCLC and breast tumors by immunostaining. We conclude that methylation of FHIT is a frequent event in NSCLC and breast cancers and is an important mechanism for loss of expression of this gene. Methylation of FHIT commences during lung cancer pathogenesis and may represent a marker for risk assessment.",
author = "S. Z{\"o}chbauer-M{\"u}ller and Fong, {K. M.} and A. Maitra and S. Lam and J. Geradts and R. Ashfaq and Virmani, {A. K.} and S. Milchgrub and Gazdar, {A. F.} and Minna, {J. D.}",
year = "2001",
month = "5",
day = "1",
language = "English (US)",
volume = "61",
pages = "3581--3585",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "9",

}

TY - JOUR

T1 - 5′ CpG island methylation of the FHIT gene is correlated with loss of gene expression in lung and breast cancer

AU - Zöchbauer-Müller, S.

AU - Fong, K. M.

AU - Maitra, A.

AU - Lam, S.

AU - Geradts, J.

AU - Ashfaq, R.

AU - Virmani, A. K.

AU - Milchgrub, S.

AU - Gazdar, A. F.

AU - Minna, J. D.

PY - 2001/5/1

Y1 - 2001/5/1

N2 - Allele loss and loss of expression of fragile histidine triad (FHIT), a putative tumor suppressor gene located in chromosome region 3p14.2, are frequent in several types of cancers. Tumor-acquired methylation of promoter region CpG islands is one method for silencing tumor suppressor genes. We investigated 5′ CpG island methylation of the FHIT gene in 107 primary non-small cell lung cancer (NSCLC) samples and corresponding nonmalignant lung tissues, 39 primary breast carcinomas, as well as in 49 lung and 22 breast cancer cell lines by a methylation-specific PCR assay. In addition, we analyzed brushes from the bronchial epithelium of 35 heavy smokers without cancer. FHIT methylation was detected in 37% of primary NSCLCs, 31% of primary breast cancers, and 65% of lung and 86% of breast cancer cell lines. The frequency of methylation in small cell and NSCLC cell lines were identical. Methylation was found in 9% of the corresponding nonmalignant lung tissues and in 17% of bronchial brushes from heavy cigarette smokers. FHIT methylation was significantly correlated with loss of FHIT mRNA expression by Northern blot analysis in lung cancer cell lines and with loss of Fhit expression in NSCLC and breast tumors by immunostaining. We conclude that methylation of FHIT is a frequent event in NSCLC and breast cancers and is an important mechanism for loss of expression of this gene. Methylation of FHIT commences during lung cancer pathogenesis and may represent a marker for risk assessment.

AB - Allele loss and loss of expression of fragile histidine triad (FHIT), a putative tumor suppressor gene located in chromosome region 3p14.2, are frequent in several types of cancers. Tumor-acquired methylation of promoter region CpG islands is one method for silencing tumor suppressor genes. We investigated 5′ CpG island methylation of the FHIT gene in 107 primary non-small cell lung cancer (NSCLC) samples and corresponding nonmalignant lung tissues, 39 primary breast carcinomas, as well as in 49 lung and 22 breast cancer cell lines by a methylation-specific PCR assay. In addition, we analyzed brushes from the bronchial epithelium of 35 heavy smokers without cancer. FHIT methylation was detected in 37% of primary NSCLCs, 31% of primary breast cancers, and 65% of lung and 86% of breast cancer cell lines. The frequency of methylation in small cell and NSCLC cell lines were identical. Methylation was found in 9% of the corresponding nonmalignant lung tissues and in 17% of bronchial brushes from heavy cigarette smokers. FHIT methylation was significantly correlated with loss of FHIT mRNA expression by Northern blot analysis in lung cancer cell lines and with loss of Fhit expression in NSCLC and breast tumors by immunostaining. We conclude that methylation of FHIT is a frequent event in NSCLC and breast cancers and is an important mechanism for loss of expression of this gene. Methylation of FHIT commences during lung cancer pathogenesis and may represent a marker for risk assessment.

UR - http://www.scopus.com/inward/record.url?scp=0035324425&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035324425&partnerID=8YFLogxK

M3 - Article

C2 - 11325823

AN - SCOPUS:0035324425

VL - 61

SP - 3581

EP - 3585

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 9

ER -