RESEARCH COMMUNICATION Loss of DBC2 Expression is an Early and Progressive Event in the Development of Lung Adenocarcinoma

Lung cancer is currently the leading cause of cancerrelated death in most Asian countries and the world (Merel Kimman et al., 2012), of which adenocarcinoma accounts for more than 50% of all cases (Pao and Girard, 2011). Lung adenocarcinoma is of diverse subtypes, the new classification includes pre-invasive lesions, minimally invasive adenocarcinoma, invasive adenocarcinoma and some variants (Travis et al., 2011). A growing group of research supports a multistep process model in lung adenocarcinoma development, during which genetic mutations are sequentially accumulated (Raz et al., 2006). For some tumor suppressor genes, like P53, of which the incidence of mutation varies with the histological types, there was a trend that more mutation occurred as the adenocarcinoma turns to be more invasive (Koga et al., 2001). Recently, DBC2 is isolated as a tumor suppressor gene from human chromosome 8p21, and it is the best candidate tumor suppressor gene from this region (Hamaguchi et al., 2002). Incidence of DBC2 losses has been detected in various carcinomas including prostate, breast, lung, colon, rectum, bladder, liver and larynx carcinoma (Emi et al., 1992; Lundgren et al., 1992; Bova et al., 1993; Fujiwara et al., 1993; Sunwoo et al., 1996). In lung carcinoma, there was a report that the allelic losses at chromosome 8p21-23 were over 80% (17 of 21) (Wistuba et al., 1999). Accumulating evidence suggested that DBC2 may play an important part in the carcinogenic process by down