Molecular Genetic Characterizations of Human Non-Small Cell Lung Cancer

Lung cancer is one of the most common malignances worldwide. It is the first leading cause of cancer death in both men and women in Hong Kong and in the United States. The prognosis of this prevalent disease is poor with a 5-year survival rate at about 15%. A better understanding of the underlying genetic molecular mechanism is crucial and essential for better diagnosis and therapeutic design purposes for cancer treatment. However, a clear molecular machinery for the carcinogenesis remains far to be discovered.
In this study, genetic alterations of non-small cell lung cancer, the major subtype of human lung cancer were extensively studied. By using comparative genomic hybridization, the most frequent chromosomal regions showing DNA copy number gains and losses were investigated. Besides, patterns of chromosomal aberrations between adenocarcinoma and squamous cell carcinoma of NSCLC were compared and found to be greatly different. Results indicated that chromosome 3q gain is the most prominent difference between the two sub-groups (p
Association between genetic alterations and clinical significance was also investigated. Interestingly, we found that gains of chromosomes 5p and 20q and loss of 5q were significantly correlated to the advanced stage of NSCLC (p
We have established three human primary NSCLC cell lines and performed cytogenetic and molecular characterization of each. All of the three cells exhibited complex numerical and structural chromosomal changes. EGFR and FGF3 were found to be highly amplified and expressed in one of the NSCLC cell line. By studying protein expression in large sample population profile, we were the first to report the expression of FGF3 in NSCLC. Here we demonstrated the use of in vitro cell model for cancer-related genes identification and provide tools for further mechanistic and functional study.
Apart from chromosomal gains, regions with DNA loss are also the study targets in tumorgenesis investigation. According to our CGH results, chromosome 3p is the region found with the most frequent copy number loss. Here we reported the use of SNP markers for high resolution 3p allelic loss study using Sequenom platform. Our data serve the basis for putative tumor suppressor genes identification in the future. An abstract of 412 words
DOI: 10.5353/th_b3137531
Subjects:
Lungs - Cancer - Genetic aspects
Molecular genetics