Allelic imbalance in 1p, 7q, 9p, 11p, 12q and 16q regions in non-small cell lung carcinoma and its clinical association: a pilot study

作者：Czarnecka Karolina H; Migdalska Sek Monika; Antczak Adam; Pastuszak Lewandoska Dorota; Kordiak Jacek; Nawrot Ewa; Domanska Daria; Kaleta Dorota; Gorski Pawe; Brzezianska Ewa Barbara^*

来源：Molecular Biology Reports, 2013, 40(12): 6671-6684.

DOI：10.1007/s11033-013-2782-1

• Non-small cell lung carcinoma (NSCLC)
• Loss of heterozygosity (LOH)
• Microsatellite instability (MSI)
• Microsatellite markers
• Genetic instability

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; chi(2) test). The associations of total LOH/MSI frequency: 1) increase in 11p15.5 region (p = 0.047; chi(2) test) and 2) decrease in 7q32.2 region (p = 0.037; chi(2) 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.

• 出版日期2013-12