title: Aberrant methylation of FBN2 in human non-small cell lung cancer.
abstract: FBN2, a large modular extracellular matrix glycoprotein, is known to be a key component of human elastic fiber. A loss of FBN2 expression due to promoter methylation was recently identified in pancreatic cancer. We examined FBN2 expression by reverse transcription PCR and aberrant methylation of FBN2 by methylation specific PCR in lung cancer cell lines. Aberrant methylation of FBN2 was present in 55% (6 of 11) of non-small cell lung cancer (NSCLC) cell lines, but it absent in small cell lung cancer cell lines. The concordance between loss of expression and aberrant methylation of FBN2 was 88% (14 of 16) in the cell lines. FBN2 expression was restored after treatment with the demethylating agent, 5-aza-2'-deoxycytidine in all six cell lines tested that lacked FBN2 expression. Among primary NSCLC, 49% (62/126) of cases had FBN2 methylation, but only 7% (5/69) of the corresponding nonmalignant lung tissues had it. Although FBN2 methylation was detected even in patients with early stage disease, it occurred frequently in large tumors (p=0.022), with nodal metastasis (p=0.037), or with advanced stages of NSCLC (p=0.014). Methylation and silencing of FBN2 in tumor cells may play an important role in carcinogenesis, invasion, and metastasis of NSCLC.
authors.affiliation: Division of Thoracic Diseases, Chiba Cancer Center, 666-2, Nitona, Chuoh-ku, Chiba 260-8717, Japan.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.forename: Makoto
authors.initials: M
authors.lastname: Suzuki
authors.forename: Yohko
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Miki
authors.initials: M
authors.lastname: Ohira
authors.forename: Soichiro
authors.initials: S
authors.lastname: Ando
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Iida
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakajima
authors.forename: Akira
authors.initials: A
authors.lastname: Nakagawara
authors.forename: Hideki
authors.initials: H
authors.lastname: Kimura
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D019175:DNA Methylation; D005260:Female; D000071840:Fibrillin-2; D000071837:Fibrillins; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics; D009367:Neoplasm Staging; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: C000605723:FBN2 protein, human; D000071840:Fibrillin-2; D000071837:Fibrillins; D008840:Microfilament Proteins