Expression of DMBT1, a candidate tumor suppressor gene, is frequently lost in lung cancer

Weiguo Wu, Bonnie L. Kemp, Monja L. Proctor, Adi F. Gazdar, John D. Minna, Waun Ki Hong, Li Mao

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

DMBT1 is a candidate tumor suppressor gene located at 10q25.3-26.1. Homozygous deletion of the gene was found in a subset of medulloblastoma and glioblastoma multiforme; lack of expression was noted in the majority of these tumors. In adult tissues, DMBT1 is highly expressed only in lung and small intestine tissues, indicating its important role in these organs. By analyzing lung cancer cell lines and primary lung tumors using reverse transcription-PCR, we found that 100% (20 of 20) of small cell lung cancer (SCLC) cell lines and 43% (6 of 14) of non-small cell lung cancer (NSCLC) cell lines lacked DMBT1 expression. Furthermore, 45% (9 of 20) of the primary NSCLCs exhibited a markedly low level of gene expression compared with corresponding normal lung tissues, indicating that lack of gene expression also occurs in primary lung cancers. To determine the potential mechanisms for lack of DMBT1 expression in lung cancer, we analyzed tumor cell lines for potential intragenic homozygous deletions of the gene and found such homozygous deletions in 10% (4 of 40) of SCLC cell lines but in none of 14 NSCLC cell lines. Moreover, the loss of expression could not be rescued by treatment with a demethylation agent (5-azacytidine) in two NSCLC cell lines lacking DMBT1 expression, suggesting that de novo methylation of the promoter region of the gene is unlikely to play a role in inactivation of the gene. We then sequenced the whole coding region of DMBT1 in 8 NSCLC cell lines that expressed DMBT1 and 20 primary NSCLCs. A potential point mutation at codon 52 was detected in a NSCLC cell line and resulted in an amino acid change from serine to tryptophan. Three common polymorphisms were also detected in tissues analyzed. Our data demonstrate that DMBT1 expression is frequently lost in lung cancer due to gene deletion and to other not yet identified mechanisms, suggesting that inactivation of DMBT1 may play an important role in lung tumorigenesis.

Original languageEnglish (US)
Pages (from-to)1846-1851
Number of pages6
JournalCancer Research
Volume59
Issue number8
StatePublished - Apr 15 1999

Fingerprint

Tumor Suppressor Genes
Lung Neoplasms
Cell Line
Non-Small Cell Lung Carcinoma
Gene Deletion
Lung
Small Cell Lung Carcinoma
Gene Expression
Azacitidine
Medulloblastoma
Gene Silencing
Glioblastoma
Tumor Cell Line
Point Mutation
Genetic Promoter Regions
Codon
Tryptophan
Serine
Methylation
Reverse Transcription

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Wu, W., Kemp, B. L., Proctor, M. L., Gazdar, A. F., Minna, J. D., Hong, W. K., & Mao, L. (1999). Expression of DMBT1, a candidate tumor suppressor gene, is frequently lost in lung cancer. Cancer Research, 59(8), 1846-1851.

Expression of DMBT1, a candidate tumor suppressor gene, is frequently lost in lung cancer. / Wu, Weiguo; Kemp, Bonnie L.; Proctor, Monja L.; Gazdar, Adi F.; Minna, John D.; Hong, Waun Ki; Mao, Li.

In: Cancer Research, Vol. 59, No. 8, 15.04.1999, p. 1846-1851.

Research output: Contribution to journalArticle

Wu, W, Kemp, BL, Proctor, ML, Gazdar, AF, Minna, JD, Hong, WK & Mao, L 1999, 'Expression of DMBT1, a candidate tumor suppressor gene, is frequently lost in lung cancer', Cancer Research, vol. 59, no. 8, pp. 1846-1851.
Wu, Weiguo ; Kemp, Bonnie L. ; Proctor, Monja L. ; Gazdar, Adi F. ; Minna, John D. ; Hong, Waun Ki ; Mao, Li. / Expression of DMBT1, a candidate tumor suppressor gene, is frequently lost in lung cancer. In: Cancer Research. 1999 ; Vol. 59, No. 8. pp. 1846-1851.
@article{352b4fb07ec24672b55401716b2485f9,
title = "Expression of DMBT1, a candidate tumor suppressor gene, is frequently lost in lung cancer",
abstract = "DMBT1 is a candidate tumor suppressor gene located at 10q25.3-26.1. Homozygous deletion of the gene was found in a subset of medulloblastoma and glioblastoma multiforme; lack of expression was noted in the majority of these tumors. In adult tissues, DMBT1 is highly expressed only in lung and small intestine tissues, indicating its important role in these organs. By analyzing lung cancer cell lines and primary lung tumors using reverse transcription-PCR, we found that 100{\%} (20 of 20) of small cell lung cancer (SCLC) cell lines and 43{\%} (6 of 14) of non-small cell lung cancer (NSCLC) cell lines lacked DMBT1 expression. Furthermore, 45{\%} (9 of 20) of the primary NSCLCs exhibited a markedly low level of gene expression compared with corresponding normal lung tissues, indicating that lack of gene expression also occurs in primary lung cancers. To determine the potential mechanisms for lack of DMBT1 expression in lung cancer, we analyzed tumor cell lines for potential intragenic homozygous deletions of the gene and found such homozygous deletions in 10{\%} (4 of 40) of SCLC cell lines but in none of 14 NSCLC cell lines. Moreover, the loss of expression could not be rescued by treatment with a demethylation agent (5-azacytidine) in two NSCLC cell lines lacking DMBT1 expression, suggesting that de novo methylation of the promoter region of the gene is unlikely to play a role in inactivation of the gene. We then sequenced the whole coding region of DMBT1 in 8 NSCLC cell lines that expressed DMBT1 and 20 primary NSCLCs. A potential point mutation at codon 52 was detected in a NSCLC cell line and resulted in an amino acid change from serine to tryptophan. Three common polymorphisms were also detected in tissues analyzed. Our data demonstrate that DMBT1 expression is frequently lost in lung cancer due to gene deletion and to other not yet identified mechanisms, suggesting that inactivation of DMBT1 may play an important role in lung tumorigenesis.",
author = "Weiguo Wu and Kemp, {Bonnie L.} and Proctor, {Monja L.} and Gazdar, {Adi F.} and Minna, {John D.} and Hong, {Waun Ki} and Li Mao",
year = "1999",
month = "4",
day = "15",
language = "English (US)",
volume = "59",
pages = "1846--1851",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "8",

}

TY - JOUR

T1 - Expression of DMBT1, a candidate tumor suppressor gene, is frequently lost in lung cancer

AU - Wu, Weiguo

AU - Kemp, Bonnie L.

AU - Proctor, Monja L.

AU - Gazdar, Adi F.

AU - Minna, John D.

AU - Hong, Waun Ki

AU - Mao, Li

PY - 1999/4/15

Y1 - 1999/4/15

N2 - DMBT1 is a candidate tumor suppressor gene located at 10q25.3-26.1. Homozygous deletion of the gene was found in a subset of medulloblastoma and glioblastoma multiforme; lack of expression was noted in the majority of these tumors. In adult tissues, DMBT1 is highly expressed only in lung and small intestine tissues, indicating its important role in these organs. By analyzing lung cancer cell lines and primary lung tumors using reverse transcription-PCR, we found that 100% (20 of 20) of small cell lung cancer (SCLC) cell lines and 43% (6 of 14) of non-small cell lung cancer (NSCLC) cell lines lacked DMBT1 expression. Furthermore, 45% (9 of 20) of the primary NSCLCs exhibited a markedly low level of gene expression compared with corresponding normal lung tissues, indicating that lack of gene expression also occurs in primary lung cancers. To determine the potential mechanisms for lack of DMBT1 expression in lung cancer, we analyzed tumor cell lines for potential intragenic homozygous deletions of the gene and found such homozygous deletions in 10% (4 of 40) of SCLC cell lines but in none of 14 NSCLC cell lines. Moreover, the loss of expression could not be rescued by treatment with a demethylation agent (5-azacytidine) in two NSCLC cell lines lacking DMBT1 expression, suggesting that de novo methylation of the promoter region of the gene is unlikely to play a role in inactivation of the gene. We then sequenced the whole coding region of DMBT1 in 8 NSCLC cell lines that expressed DMBT1 and 20 primary NSCLCs. A potential point mutation at codon 52 was detected in a NSCLC cell line and resulted in an amino acid change from serine to tryptophan. Three common polymorphisms were also detected in tissues analyzed. Our data demonstrate that DMBT1 expression is frequently lost in lung cancer due to gene deletion and to other not yet identified mechanisms, suggesting that inactivation of DMBT1 may play an important role in lung tumorigenesis.

AB - DMBT1 is a candidate tumor suppressor gene located at 10q25.3-26.1. Homozygous deletion of the gene was found in a subset of medulloblastoma and glioblastoma multiforme; lack of expression was noted in the majority of these tumors. In adult tissues, DMBT1 is highly expressed only in lung and small intestine tissues, indicating its important role in these organs. By analyzing lung cancer cell lines and primary lung tumors using reverse transcription-PCR, we found that 100% (20 of 20) of small cell lung cancer (SCLC) cell lines and 43% (6 of 14) of non-small cell lung cancer (NSCLC) cell lines lacked DMBT1 expression. Furthermore, 45% (9 of 20) of the primary NSCLCs exhibited a markedly low level of gene expression compared with corresponding normal lung tissues, indicating that lack of gene expression also occurs in primary lung cancers. To determine the potential mechanisms for lack of DMBT1 expression in lung cancer, we analyzed tumor cell lines for potential intragenic homozygous deletions of the gene and found such homozygous deletions in 10% (4 of 40) of SCLC cell lines but in none of 14 NSCLC cell lines. Moreover, the loss of expression could not be rescued by treatment with a demethylation agent (5-azacytidine) in two NSCLC cell lines lacking DMBT1 expression, suggesting that de novo methylation of the promoter region of the gene is unlikely to play a role in inactivation of the gene. We then sequenced the whole coding region of DMBT1 in 8 NSCLC cell lines that expressed DMBT1 and 20 primary NSCLCs. A potential point mutation at codon 52 was detected in a NSCLC cell line and resulted in an amino acid change from serine to tryptophan. Three common polymorphisms were also detected in tissues analyzed. Our data demonstrate that DMBT1 expression is frequently lost in lung cancer due to gene deletion and to other not yet identified mechanisms, suggesting that inactivation of DMBT1 may play an important role in lung tumorigenesis.

UR - http://www.scopus.com/inward/record.url?scp=0033561511&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033561511&partnerID=8YFLogxK

M3 - Article

VL - 59

SP - 1846

EP - 1851

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 8

ER -