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Methylation of RAS association domain family protein 1A as a biomarker of lung cancer
Author(s) -
Grote Hans Juergen,
Schmiemann Viola,
Geddert Helene,
Bocking Alfred,
Kappes Rainer,
Gabbert Helmut Erich,
Sarbia Mario
Publication year - 2006
Publication title -
cancer cytopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.21717
Subject(s) - lung cancer , medicine , dna methylation , methylation , biomarker , cancer , pathology , lung , cytology , cancer research , oncology , gene , gene expression , biology , biochemistry
BACKGROUND Promoter hypermethylation is an important mechanism for silencing tumor‐suppressor genes in cancer and a promising tool for development of molecular biomarkers. This study aimed to determine the prevalence of RAS association domain family protein 1A ( RASSF1A ) promoter hypermethylation in bronchial aspirates of patients with suspected lung cancer and to test whether this type of methylation assay could be used as a diagnostic adjunct to conventional cytology. METHODS Two hundred three bronchial aspirates from patients with suspected lung cancer were analyzed for RASSF1A hypermethylation by using a sensitive quantitative methylation‐specific polymerase chain reaction (QMSP). RESULTS RASSF1A hypermethylation was found in 88% (35 of 40), 28% (31 of 111), and 100% (6 of 6) of bronchial aspirates collected from patients diagnosed with small cell lung cancer, nonsmall cell lung cancer, and combined small cell lung cancer, respectively. No hypermethylation was detected in patients diagnosed with nonneoplastic lung disease (0 of 46). Depending on histologic subtype, up to 82% of cases presenting with a negative histology showed a positive methylation assay. CONCLUSIONS The QMSP analysis of RASSF1A hypermethylation enabled a highly specific distinction between patients diagnosed with lung cancer and those with nonneoplastic lung disease. These results suggested that a QMSP assay is a promising molecular tool for diagnosis of primary lung cancer. Cancer (Cancer Cytopathol) 2006. © 2006 American Cancer Society.