DNA alterations at proto-oncogene loci and their clinical significance in operable non-small cell lung cancer

Abstract

DNA from tumor samples of 54 patients with operable non-small cell lung cancer (NSCLC) was analyzed to determine whether proto-oncogene alterations could be correlated with the clinical behavior of lung cancer. Among seven proto-oncogenes tested, changes in the copy number of Ha-ras, c-myc and c-raf-1 were found in only seven tumors. Most of them were epidermoid carcinomas without lymph node involvement (NO). In spite of a localized disease with complete surgical resection, six of these patients relapsed within a mean disease-free interval (DFI) of only 6.5 months. There is a significant correlation between DNA alterations at protooncogene loci and clinical relapse within 12 months of surgical resection ( P < 0.025). Cancer 66:733-739, 1990. N INDUSTRIALIZED COUNTRIES, Cancer lung is theI leading cause of death from cancer in men and the second leading cause in women. Despite modern diagnostic, staging and therapeutic advances, the 5-year survival rate of all cases of lung cancer does not exceed 15%. ' Patients with operable non-small cell lung cancer (NSCLC) have the best prognosis. Various parameters are predictive of the outcome of surgical resection in operable NSCLC. The current ones utilized are as follows: clinical staging and lymph node mapping, histopathologic type, and general performance of the patient.2 Although these determinants are usually helpful to predict survival, clinicians are sometimes confronted with patients with early

EZH2 Promotes Expansion of Breast Tumor Initiating Cells through Activation of RAF1-β-Catenin Signaling

“…Among the genomic loci that are highly amplified by increased expression of EZH2 (Table S3), 12p13.31 gain has been shown to correlate with basal breast cancer (Chin et al, 2006), and 17q23.1 gain is especially frequent in BRCA1 associated breast cancer (Sinclair et al, 2002). Particularly, the RAF1 gene on 3p25.2 was found recurrently amplified or rearranged in multiple human cancers, where genomic aberrant RAF1 gene often associates with cancer aggressiveness and relapse (Hajj et al, 1990). Activation of RAF-MAPK pathway is also critical to inducing EMT and metastasis, traits that are recently associated with stem cell properties (Thiery et al, 2009).…”

MEK-1 activates C-Raf through a Ras-independent mechanism

“…For example, increased C-Raf expression has been documented in acute myeloid leukemia (AML) [45], primitive neuroectodermal tumors (PNETs) [46], non-small cell lung cancer (NSCLC) [47], ovarian cancer [48], thyroid [49] and gliomas [49]. In addition, though early studies asserted that overexpression of wildtype C-Raf or MEK are not tumorigenic, more recent work indicates that targeted overexpression of wildtype C-Raf in the lung could lead to lung cancer [50–54], suggesting that overexpression of wildtype C-Raf is sufficient for inducing cellular transformation.…”

K‐Ras gene status and expression of Ras/mitogen‐activated protein kinase (MAPK) signaling molecules in ameloblastomas

“…Once activated, ERK translocates to the nucleus and activates a variety of substrates, including nuclear transcription factors (16–18). Thus, Ras/MAPK signaling pathway functions as a key regulator of cell proliferation and differentiation, and aberration of involved signaling components has been identified in a various of human tumors (16, 18–23).…”