title: Nuclear and mitochondrial DNAs microsatellite instability and mitochondrial DNA copy number in adenocarcinoma and squamous cell carcinoma of lung: a pilot study.
abstract: Mitochondrial genetic changes are considered as a key molecular step of mutations in various cancers. To clarify the role of genetic instability in lung cancer, we analyzed clinicopathological characteristics and frequencies of nuclear and mitochondrial microsatellite instability (nMSI and mtMSI), and alteration of mitochondrial DNA copy number (mtCN) in adenocarcinoma (ADC) and squamous cell carcinoma (SCC) of lung. DNA was isolated from 48 patients with ADC and 42 with SCC. Markers for nMSI, BAT 25 and 26, and markers for mtMSI, (C)n and (CA)n in mitochondrial D-loop region, were utilized. The mtCN were measured by real-time polymerase chain reaction. The nMSI was found in two patients (4.2%) of ADC and 6 (14.3%) of SCC. The mtMSI was detected in 10 patients (20.8%) of ADC and 8 (19.0%) of SCC. Mean mtCN was 5.05 ± 8.17 and 3.34 ± 5.14 in ADC and SCC respectively. The mtCN was increased in 35 patients (72.9%) of ADC and 30 (71.4%) of SCC. The mtMSI more frequently appeared in more advanced pathologic T stage in ADC (p = 0.003). Alterations of mtCN and a high frequency of mtMSI in our patient samples indicate that mitochondrial DNA is a potential molecular marker in lung cancers (ADC and SCC) correlating with their histological classification.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea.
authors.forename: Deok Heon
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Anatomy, School of Medicine, Dongsan Medical Center, Keimyung University, Daegu, Korea.
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Medical Genetics, School of Medicine, Dongsan Medical Center, Keimyung University, Daegu, Korea.
authors.forename: Dae-Kwang
authors.initials: DK
authors.lastname: Kim
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, School of Medicine, Dongsan Medical Center, Keimyung University, Daegu, Korea.
authors.forename: Dong Yoon
authors.initials: DY
authors.lastname: Keum
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000077192:Adenocarcinoma of Lung; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002467:Cell Nucleus / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D018628:Gene Dosage / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D053842:Microsatellite Instability; D018895:Microsatellite Repeats / Q000235:genetics*; D008928:Mitochondria / Q000235:genetics; D010865:Pilot Projects; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D004272:DNA, Mitochondrial
keywords: Lung cancer; microsatellite instability; mitochondrial DNA copy number