Increased Loss of Chromosome 9p21 but not p16 Inactivation in Primary Non-Small Cell Lung Cancer from Smokers

摘要: Epidemiological studies have demonstrated a causal association between tobacco use and carcinoma of the lung, some genetic targets carcinogens in cigarette smoke been defined recently. We further examined effect smoking on frequency allelic losses chromosome 9p21 incidence p16 inactivation. Chromosomal loss at 9p21-24 was determined by microsatellite analysis using 14 markers 47 patients with non-small cell lung cancer. In addition, gene inactivation DNA sequence analysis, methylation-specific PCR, immunohistochemistry. Tumors from group nonsmokers (n = 14) were compared tumors smokers 33) matched for type, tumor stage, gender. Allelic encompassing locus present significantly (P 0.01) more often (23 33 smokers, 70%) than (4 nonsmokers, 28%). No significant differences observed (45% versus 36%). However, homozygous deletion point mutation only whereas inactivated through promoter hypermethylation. Thus, is common event all cancer, but mechanism alteration differs nonsmokers. The link identifies additional pathogenesis