title: Significant frequency of allelic imbalance in 3p region covering RARβ and MLH1 loci seems to be essential in molecular non-small cell lung cancer diagnosis.
abstract: The aim of the study was to investigate the influence of allelic imbalance (AI) in several loci of tumor suppressor genes in 3p region on the non-small cell lung cancer (NSCLC) development. We evaluated the frequency of loss of heterozygosity and/or microsatellite imbalance (LOH/MSI) and assessed their association with patients' characteristics (age, gender, tobacco addiction) and NSCLC classification according to TNM/AJCC staging. To analyze the potential role of AI involved in NSCLC pathogenesis, we allelotyped a group of 74 NSCLC patients using 7 microsatellite markers. The highest frequency of LOH/MSI, however, not statistically significant, was observed in RARβ and MLH1 (p = 0.104 and p = 0.216, respectively) loci. The association between high LOH/MSI frequency in 3p region with male gender (p = 0.041) as well as with age (especially >60 years) for RARβ and MLH1 genes (p = 0.0001 and p = 0.020, respectively) was documented. Statistically significant increased frequency of MLH1 allelic loss in squamous cell carcinoma (SCC) versus non-squamous cell carcinoma (non-SCC) was observed (p = 0.01). Significant increase in LOH/MSI frequency in 3p region (mainly in FHIT and MLH1 loci) in correlation with cigarette addiction in a lifetime (≥40 years and ≥40 Pack Years) was also documented (p < 0.05). The highest LOH/MSI was revealed in RARβ locus in IA tumors (p = 0.0001), while the similarly high allelic loss of MLH1 correlated with III A/B tumors (p = 0.0002), according to AJCC staging. The obtained results demonstrate that AI is influenced by tobacco smoking and seems to be vital in the molecular diagnosis of NSCLC, especially of SCC subtype.
authors.affiliation: Department of General and Oncological Pulmonology, Medical University of Lodz, Kopcińskiego St.22, 90-153 Lodz, Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Antczak
authors.forename: Monika
authors.initials: M
authors.lastname: Migdalska-Sęk
authors.forename: Dorota
authors.initials: D
authors.lastname: Pastuszak-Lewandoska
authors.forename: Karolina
authors.initials: K
authors.lastname: Czarnecka
authors.forename: Ewa
authors.initials: E
authors.lastname: Nawrot
authors.forename: Daria
authors.initials: D
authors.lastname: Domańska
authors.forename: Jacek
authors.initials: J
authors.lastname: Kordiak
authors.forename: Paweł
authors.initials: P
authors.lastname: Górski
authors.forename: Ewa
authors.initials: E
authors.lastname: Brzeziańska
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D022981:Allelic Imbalance / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000172:deficiency / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056426:Genetic Loci / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics*; D018168:Receptors, Retinoic Acid / Q000172:deficiency / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D018168:Receptors, Retinoic Acid; C082925:retinoic acid receptor beta; D000070957:MutL Protein Homolog 1