Abstract
In lung cancer pathogenesis, genetic instability, i.e., loss of heterozygosity (LOH) and microsatellite instability (MSI) is a frequent molecular event, occurring at an early stage of cancerogenesis. The presence of LOH/MSI in non-small cell lung carcinoma (NSCLC) was found in many chromosomal regions, but exclusive of 3p their diagnostic value remains controversial. In this study we focused on other than 3p regions—1p31.2, 7q32.2, 9p21.3, 11p15.5, 12q23.2 and 16q22—the loci of many oncogenes and tumour suppressor genes. To analyze the potential role of LOH/MSI involved in NSCLC pathogenesis we allelotyped a panel of 13 microsatellite markers in a group of 56 cancer specimens. Our data demonstrate the presence of allelic loss for all (13) analyzed markers. Total LOH/MSI frequency in NSCLC was the highest for chromosomal region 11p15.5 (25.84 %), followed by 9p21.3 and 1p31.2 (19.87 and 16.67 % respectively). A statistically significant increase of total LOH/MSI frequency was detected for the 11p15.5 region (p = 0.0301; χ2 test). The associations of total LOH/MSI frequency: 1) increase in 11p15.5 region (p = 0.047; χ2 test) and 2) decrease in 7q32.2 region (p = 0.037; χ2 test) have been statistically significant in AJCC III (American Joint Committee on Cancer Staging). In Fractional Allele Loss (FAL) index analysis, the correlation with cigarette addiction has been statistically significant. The increased amount of cigarettes smoked (pack years) in a lifetime correlates with increasing FAL (p = 0.024; Kruskal–Wallis test). These results demonstrate that LOH/MSI alternation in studied chromosomal regions is strongly influenced by tobacco smoking but do not seem to be pivotal NSCLC diagnostic marker with prognostic impact.
Highlights
Lung cancer is one of the leading causes of cancer mortality and morbidity in most developed countries and the most common cause of death from malignant tumours worldwide in man between the ages of 50 and 70 [1, 2]
The increased amount of cigarettes smoked in a lifetime correlates with increasing Fractional Allele Loss (FAL) (p = 0.024; Kruskal–Wallis test). These results demonstrate that loss of heterozygosity (LOH)/microsatellite instability (MSI) alternation in studied chromosomal regions is strongly influenced by tobacco smoking but do not seem to be pivotal non-small cell lung carcinoma (NSCLC) diagnostic marker with prognostic impact
Lung cancer is classified into two major groups based on its biology, therapy and prognosis: non-small cell lung carcinoma (NSCLC), representing approximately 75 % of all primary lung cancers and small cell lung carcinomas (SCLC), accounting
Summary
Lung cancer is one of the leading causes of cancer mortality and morbidity in most developed countries and the most common cause of death from malignant tumours worldwide in man between the ages of 50 and 70 [1, 2]. The major histological and clinical types of NSCLC are squamous cell carcinoma (SCC); adenocarcinoma (AC) and large cell carcinoma (LCC) [3, 4]. The most important risk factor in lung cancer development is tobacco smoking, including second-hand smoke. Many molecular alterations (including mutations, polymorphisms, expression changes due to promoter hypermethylation) in many genes localized in different chromosomal regions have been proposed as leading to NSCLC development [8]. These genes are recognized as important in cell cycle regulation, proliferation, survival and metastasis (e.g. KRAS, BRAF, TP53, MYC, CCND1, EGFR, ERBB2 or BCL2) [9, 10]
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