Open AccessLung cancer with loss of BRG 1/ BRM , shows epithelial mesenchymal transition phenotype and distinct histologic and genetic features
Author(s) -
Matsubara Daisuke,
Kishaba Yuka,
Ishikawa Shumpei,
Sakatani Takashi,
Oguni Sachiko,
Tamura Tomoko,
Hoshino Hiroko,
Sugiyama Yukihiko,
Endo Shunsuke,
Murakami Yoshinori,
Aburatani Hiroyuki,
Fukayama Masashi,
Niki Toshiro
Publication year - 2013
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12065
Subject(s) - cancer research , vimentin , biology , adenocarcinoma , epithelial–mesenchymal transition , carcinogenesis , immunohistochemistry , pathology , lung cancer , phenotype , cancer , metastasis , medicine , immunology , genetics , gene , biochemistry
BRG 1 and BRM , two core catalytic subunits in SWI / SNF chromatin remodeling complexes, have been suggested as tumor suppressors, yet their roles in carcinogenesis are unclear. Here, we present evidence that loss of BRG 1 and BRM is involved in the progression of lung adenocarcinomas. Analysis of 15 lung cancer cell lines indicated that BRG 1 mutations correlated with loss of BRG 1 expression and that loss of BRG 1 and BRM expression was frequent in E ‐cadherin‐low and vimentin‐high cell lines. Immunohistochemical analysis of 93 primary lung adenocarcinomas showed loss of BRG 1 and BRM in 11 (12%) and 16 (17%) cases, respectively. Loss of expression of BRG 1 and BRM was frequent in solid predominant adenocarcinomas and tumors with low thyroid transcription factor‐1 ( TTF ‐1, master regulator of lung) and low cytokeratin7 and E ‐cadherin (two markers for bronchial epithelial differentiation). Loss of BRG 1 was correlated with the absence of lepidic growth patterns and was mutually exclusive of epidermal growth factor receptor ( EGFR ) mutations. In contrast, loss of BRM was found concomitant with lepidic growth patterns and EGFR mutations. Finally, we analyzed the publicly available dataset of 442 cases and found that loss of BRG 1 and BRM was frequent in E ‐cadherin‐low, TTF ‐1‐low, and vimentin‐high cases and correlated with poor prognosis. We conclude that loss of either or both BRG 1 and BRM is involved in the progression of lung adenocarcinoma into solid predominant tumors with features of epithelial mesenchymal transition and loss of the bronchial epithelial phenotype. BRG 1 loss was specifically involved in the progression of EGFR wild‐type, but not EGFR ‐mutant tumors.