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View the Table of Contents for the September 1 issue of Cancer Research.
Tang et al. Page 7568
Somatic mutations of EGFR tyrosine kinase domain have been reported in subsets of lung adenocarcinomas. Mutations are clinically relevant, because they are associated with tumor sensitivity to EGFR tyrosine kinase inhibitors. Tang et al. investigated whether EGFR mutations are early events in the pathogenesis of lung adenocarcinomas by studying microdissected peripheral respiratory epithelium. Of interest, EGFR mutations were detected in normal bronchial and bronchiolar epithelium in 43% of patients with EGFR mutant adenocarcinomas. These findings indicate that EGFR mutation is an early event in lung adenocarcinoma pathogenesis, and suggest EGFR mutations as an early detection marker and chemoprevention target.
Jönsson et al. Page 7612
Mutations in BRCA1 and BRCA2 account for a significant proportion of hereditary breast cancers. Jönsson et al. established DNA copy number profiles from both freshly frozen and archival hereditary breast tumor samples by use of array CGH; mapping single copy number gains, losses, and a novel homozygous deletion. Using hierarchical clustering, inherited and sporadic tumors could be discriminated into separate groups. Moreover, using support vector machines, BRCA1 and BRCA2 tumors were correctly classified. Taken together, these results suggest that array CGH is a promising diagnostic tool in hereditary breast cancer.
van der Pluijm et al. Page 7682
Bone is continuously remodelling, and growth factors supporting bone metastatic growth are released during bone resorption. van der Pluijm et al. used whole-body bioluminescent reporter imaging for the detection, monitoring, and quantification of experimentally-induced bone metastases from human breast cancer cells. Suppression of bone turnover by bisphosphonates prior to bone colonization by cancer cells inhibited the number of developing bone metastases, but growth was affected only transiently. Reduction of bone turnover, however, had no effect on growth of established bone metastases. Therefore, cancer cells metastatic to bone become increasingly independent of micro-environmental growth factor support and progress autonomously.
Vatolin et al. Page 7751 Hong et al. Page 7763
Cancer Testis (CT) genes are normally expressed only in germ-line cells, yet are aberrantly activated in somatic cells during malignant transformation and encode proteins that are recognized by cytolytic T lymphocytes from cancer patients. To date, the mechanisms associated with de-repression of CT genes in primary cancers or induction of these genes in cultured cells following exposure to chromatin remodeling agents remain unclear. In the two complementary studies in this issue, Vatolin et al. and Hong et al. demonstrate that demethylation and derepression of MAGE-A1 and NY-ESO-1 CT genes in cultured normal fibroblasts and lung cancer cells coincides with a CTCF-to-BORIS switch of the in vivo occupancy on DNA within the regulatory regions of these CT genes. Taken together, these studies indicate the possibility that BORIS activation and subsequent binding to CT gene promoters may tether epigenetic machinery that mediates CT gene induction in various types of cancer, and suggest that induction of BORIS may represent a novel strategy to augment CT antigen expression for human cancer immunotherapy.
Dikmen et al. Page 7866
The incidence of lung adenocarcinoma, a subtype of non-small cell lung cancer (NSCLC), is increasing world-wide. The survival rate of patients with lung cancer is poor due to the metastatic nature of the disease. Dikmen et al. designed, synthesized and evaluated the telomerase template antagonist - GRN163L. This molecule inhibits telomerase activity in a dose- and sequence-dependent manner in NSCLC derived A549-Luc cells at pharmacologically doses. Treatment of cancer cells with GRN163L results in progressive telomeric shortening, and a rapid loss of ability to form robust colonies in culture and in soft agar. In vivo studies reveal that administration of GRN163L effectively prevents formation of lung tumors in an experimental metastasis xenograft murine model.