Clinicopathologic Implications of ALK Gene Copy Number Gain in Non-small Cell Lung Cancer

PURPOSE: The anaplastic lymphoma kinase (ALK) gene is a potential molecular target in non-small cell lung carcinoma (NSCLC). The clinicopathologic implication of a change in the ALK gene copy number (GCN) is unclear. MATERIALS AND METHODS: A total of 434 primary NSCLC samples were analyzed by fluorescence in situ hybridization (FISH) for ALK GCN. RESULTS: Ninety-six cases (22.1%) showed ALK GCN gain with amplification in 16 (3.7%) cases. The cases with ALK GCN gain consisted of 47 adenocarcinomas (49.0%), 41 squamous cell carcinomas (42.7%), 5 adenosquamous carcinomas (5.2%) and 3 other NSCLCs (3.1%). ALK gene amplification was identified in 7 adenocarcinomas (43.7%) and 9 squamous cell carcinomas (56.3%). There was no significant difference between ALK GCN gain/amplification and histologic subtypes. Univariate survival analysis revealed that patients with ALK GCN gain/amplification showed shorter progression-free survival durations and decreased overall survival rates (p<0.001). However, multivariate analysis proved that ALK GCN gain/amplification is not an independent prognostic factor for progression-free survival or overall survival. CONCLUSION: ALK GCN gain is frequently identified in NSCLCs and the incidence is similar among histologic subtypes. Although ALK GCN gain/amplification is not an independent prognostic marker, it is associated with tumor progression in NSCLC.

Genetic Alterations in Primary Gastric Carcinomas Correlated with Clinicopathological Variables by Array Comparative Genomic Hybridization

Genetic alterations have been recognized as an important event in the carcinogenesis of gastric cancer (GC). We conducted high resolution bacterial artificial chromosome array-comparative genomic hybridization, to elucidate in more detail the genomic alterations, and to establish a pattern of DNA copy number changes with distinct clinical variables in GC. Our results showed some correlations between novel amplified or deleted regions and clinical status. Copy-number gains were frequently detected at 1p, 5p, 7q, 8q, 11p, 16p, 20p and 20q, and losses at 1p, 2q, 4q, 5q, 7q, 9p, 14q, and 18q. Losses at 4q23, 9p23, 14q31.1, or 18q21.1 as well as a gain at 20q12 were correlated with tumor-node-metastasis tumor stage. Losses at 9p23 or 14q31.1 were associated with lymph node status. Metastasis was determined to be related to losses at 4q23 or 4q28.2, as well as losses at 4q15.2, 4q21.21, 4q 28.2, or 14q31.1, with differentiation. One of the notable aspects of this study was that the losses at 4q or 14q could be employed in the evaluation of the metastatic status of GC. Our results should provide a potential resource for the molecular cytogenetic events in GC, and should also provide clues in the hunt for genes associated with GC.