Molecular Detection of Noninvasive and Invasive Bladder Tumor Tissues and Exfoliated Cells by Aberrant Promoter Methylation of Laminin-5 Encoding Genes
| Autor: | Asha Padar, Adi F. Gazdar, Arthur I. Sagalowsky, Bogdan Czerniak, H. Barton Grossman, Ubaradka G. Sathyanarayana, Jolanta Bondaruk, Makoto Suzuki, John D. Minna, Eugene P. Frenkel, Riichiroh Maruyama |
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| Rok vydání: | 2004 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty Cell Biology Risk Factors Laminin Cell Line Tumor medicine Humans Neoplasm Invasiveness Epigenetics Neoplasm Metastasis Urothelium Promoter Regions Genetic Urinary bladder Methylation DNA Methylation Prognosis medicine.anatomical_structure Urinary Bladder Neoplasms Oncology DNA methylation Cancer cell Cancer research biology.protein |
| Zdroj: | Cancer Research. 64:1425-1430 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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