Molecular Detection of Noninvasive and Invasive Bladder Tumor Tissues and Exfoliated Cells by Aberrant Promoter Methylation of Laminin-5 Encoding Genes

Ubaradka G. Sathyanarayana, Riichiroh Maruyama, Asha Padar, Makoto Suzuki, Jolanta Bondaruk, Arthur I Sagalowsky, John D Minna, Eugene P Frenkel, H. Barton Grossman, Bogdan Czerniak, Adi F Gazdar

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Laminin-5 (LN5) anchors epithelial cells to the underlying basement membrane, and it is encoded by three distinct genes: LAMA3, LAMB3, and LAMC2. To metastasize and grow, cancer cells must invade and destroy the basement membrane. Our previous work has shown that epigenetic inactivation is a major mechanism of silencing LN5 genes in lung cancers. We extended our methylation studies to resected bladder tumors (n = 128) and exfoliated cell samples (bladder washes and voided urine; n = 71) and correlated the data with clinicopathologic findings. Nonmalignant urothelium had uniform expression of LN5 genes and lacked methylation. The methylation frequencies for LN5 genes in tumors were 21-45%, and there was excellent concordance between methylation in tumors and corresponding exfoliated cells. Methylation of LAMA3 and LAMB3 and the methylation index were correlated significantly with several parameters of poor prognosis (tumor grade, growth pattern, muscle invasion, tumor stage, and ploidy pattern), whereas methylation of LAMC2 and methylation index were associated with shortened patient survival. Of particular interest, methylation frequencies of LAMA3 helped to distinguish invasive (72%) from noninvasive (12%) tumors. These results suggest that methylation of LN5 genes has potential clinical applications in bladder cancers.

Original languageEnglish (US)
Pages (from-to)1425-1430
Number of pages6
JournalCancer Research
Volume64
Issue number4
DOIs
StatePublished - Feb 15 2004

Fingerprint

Urinary Bladder Neoplasms
Methylation
Genes
Neoplasms
Basement Membrane
kalinin
Urothelium
Ploidies
Epigenomics
Lung Neoplasms
Urinary Bladder
Epithelial Cells
Urine
Muscles
Survival
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Molecular Detection of Noninvasive and Invasive Bladder Tumor Tissues and Exfoliated Cells by Aberrant Promoter Methylation of Laminin-5 Encoding Genes. / Sathyanarayana, Ubaradka G.; Maruyama, Riichiroh; Padar, Asha; Suzuki, Makoto; Bondaruk, Jolanta; Sagalowsky, Arthur I; Minna, John D; Frenkel, Eugene P; Grossman, H. Barton; Czerniak, Bogdan; Gazdar, Adi F.

In: Cancer Research, Vol. 64, No. 4, 15.02.2004, p. 1425-1430.

Research output: Contribution to journalArticle

Sathyanarayana, UG, Maruyama, R, Padar, A, Suzuki, M, Bondaruk, J, Sagalowsky, AI, Minna, JD, Frenkel, EP, Grossman, HB, Czerniak, B & Gazdar, AF 2004, 'Molecular Detection of Noninvasive and Invasive Bladder Tumor Tissues and Exfoliated Cells by Aberrant Promoter Methylation of Laminin-5 Encoding Genes', Cancer Research, vol. 64, no. 4, pp. 1425-1430. https://doi.org/10.1158/0008-5472.CAN-03-0701
Sathyanarayana, Ubaradka G. ; Maruyama, Riichiroh ; Padar, Asha ; Suzuki, Makoto ; Bondaruk, Jolanta ; Sagalowsky, Arthur I ; Minna, John D ; Frenkel, Eugene P ; Grossman, H. Barton ; Czerniak, Bogdan ; Gazdar, Adi F. / Molecular Detection of Noninvasive and Invasive Bladder Tumor Tissues and Exfoliated Cells by Aberrant Promoter Methylation of Laminin-5 Encoding Genes. In: Cancer Research. 2004 ; Vol. 64, No. 4. pp. 1425-1430.
@article{735e610725af4a8985aca5ef17308a2a,
title = "Molecular Detection of Noninvasive and Invasive Bladder Tumor Tissues and Exfoliated Cells by Aberrant Promoter Methylation of Laminin-5 Encoding Genes",
abstract = "Laminin-5 (LN5) anchors epithelial cells to the underlying basement membrane, and it is encoded by three distinct genes: LAMA3, LAMB3, and LAMC2. To metastasize and grow, cancer cells must invade and destroy the basement membrane. Our previous work has shown that epigenetic inactivation is a major mechanism of silencing LN5 genes in lung cancers. We extended our methylation studies to resected bladder tumors (n = 128) and exfoliated cell samples (bladder washes and voided urine; n = 71) and correlated the data with clinicopathologic findings. Nonmalignant urothelium had uniform expression of LN5 genes and lacked methylation. The methylation frequencies for LN5 genes in tumors were 21-45{\%}, and there was excellent concordance between methylation in tumors and corresponding exfoliated cells. Methylation of LAMA3 and LAMB3 and the methylation index were correlated significantly with several parameters of poor prognosis (tumor grade, growth pattern, muscle invasion, tumor stage, and ploidy pattern), whereas methylation of LAMC2 and methylation index were associated with shortened patient survival. Of particular interest, methylation frequencies of LAMA3 helped to distinguish invasive (72{\%}) from noninvasive (12{\%}) tumors. These results suggest that methylation of LN5 genes has potential clinical applications in bladder cancers.",
author = "Sathyanarayana, {Ubaradka G.} and Riichiroh Maruyama and Asha Padar and Makoto Suzuki and Jolanta Bondaruk and Sagalowsky, {Arthur I} and Minna, {John D} and Frenkel, {Eugene P} and Grossman, {H. Barton} and Bogdan Czerniak and Gazdar, {Adi F}",
year = "2004",
month = "2",
day = "15",
doi = "10.1158/0008-5472.CAN-03-0701",
language = "English (US)",
volume = "64",
pages = "1425--1430",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "4",

}

TY - JOUR

T1 - Molecular Detection of Noninvasive and Invasive Bladder Tumor Tissues and Exfoliated Cells by Aberrant Promoter Methylation of Laminin-5 Encoding Genes

AU - Sathyanarayana, Ubaradka G.

AU - Maruyama, Riichiroh

AU - Padar, Asha

AU - Suzuki, Makoto

AU - Bondaruk, Jolanta

AU - Sagalowsky, Arthur I

AU - Minna, John D

AU - Frenkel, Eugene P

AU - Grossman, H. Barton

AU - Czerniak, Bogdan

AU - Gazdar, Adi F

PY - 2004/2/15

Y1 - 2004/2/15

N2 - Laminin-5 (LN5) anchors epithelial cells to the underlying basement membrane, and it is encoded by three distinct genes: LAMA3, LAMB3, and LAMC2. To metastasize and grow, cancer cells must invade and destroy the basement membrane. Our previous work has shown that epigenetic inactivation is a major mechanism of silencing LN5 genes in lung cancers. We extended our methylation studies to resected bladder tumors (n = 128) and exfoliated cell samples (bladder washes and voided urine; n = 71) and correlated the data with clinicopathologic findings. Nonmalignant urothelium had uniform expression of LN5 genes and lacked methylation. The methylation frequencies for LN5 genes in tumors were 21-45%, and there was excellent concordance between methylation in tumors and corresponding exfoliated cells. Methylation of LAMA3 and LAMB3 and the methylation index were correlated significantly with several parameters of poor prognosis (tumor grade, growth pattern, muscle invasion, tumor stage, and ploidy pattern), whereas methylation of LAMC2 and methylation index were associated with shortened patient survival. Of particular interest, methylation frequencies of LAMA3 helped to distinguish invasive (72%) from noninvasive (12%) tumors. These results suggest that methylation of LN5 genes has potential clinical applications in bladder cancers.

AB - Laminin-5 (LN5) anchors epithelial cells to the underlying basement membrane, and it is encoded by three distinct genes: LAMA3, LAMB3, and LAMC2. To metastasize and grow, cancer cells must invade and destroy the basement membrane. Our previous work has shown that epigenetic inactivation is a major mechanism of silencing LN5 genes in lung cancers. We extended our methylation studies to resected bladder tumors (n = 128) and exfoliated cell samples (bladder washes and voided urine; n = 71) and correlated the data with clinicopathologic findings. Nonmalignant urothelium had uniform expression of LN5 genes and lacked methylation. The methylation frequencies for LN5 genes in tumors were 21-45%, and there was excellent concordance between methylation in tumors and corresponding exfoliated cells. Methylation of LAMA3 and LAMB3 and the methylation index were correlated significantly with several parameters of poor prognosis (tumor grade, growth pattern, muscle invasion, tumor stage, and ploidy pattern), whereas methylation of LAMC2 and methylation index were associated with shortened patient survival. Of particular interest, methylation frequencies of LAMA3 helped to distinguish invasive (72%) from noninvasive (12%) tumors. These results suggest that methylation of LN5 genes has potential clinical applications in bladder cancers.

UR - http://www.scopus.com/inward/record.url?scp=10744226784&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=10744226784&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-03-0701

DO - 10.1158/0008-5472.CAN-03-0701

M3 - Article

C2 - 14973053

AN - SCOPUS:10744226784

VL - 64

SP - 1425

EP - 1430

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 4

ER -