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Kim, Kim, Kim, Oh, Park, Jeong, Kim, Lim, Park, and Kim: Microsatellite Alterations of Plasma DNA in Non-Small Cell Lung Cancer
Original Article

Tuberculosis and Respiratory Diseases 2005; 58(4): 352-358.

Published online: 30 April 2005

DOI: https://doi.org/10.4046/trd.2005.58.4.352

Microsatellite Alterations of Plasma DNA in Non-Small Cell Lung Cancer

Kyu-Sik Kim, M.D.1, 2, Eun-Jung Kim, M.D.2, Soo-Ock Kim, M.D.2, In-Jae Oh, M.D.2, Chang-Min Park, M.D.2, Ju-Yeon Jeong, M.D.1, 2, Yu-Il Kim, M.D.2, Sung-Chul Lim, M.D.2, Jong-Tae Park3, Young-Chul Kim, M.D.1, 2

1Lung and Esophageal Cancer Clinic, Chonnam National University Hwasun Hospital, Korea.

2Department of Pulmonology and Critical Care Medicine, Chonnam National University Medical School, South Korea.

3Department of Forensic Medicine, Chonnam National University Medical School, South Korea.

Address for correspondence: Young-Chul Kim, M.D. Lung and Esophageal Cancer Clinic Department of Pulmonology and Critical Care Medicine Chonnam Natioinal University Hwasun Hospital Jeollanamdo, Hwasun, Ilsim-ri 160, 519-809, Korea. Phone: 82-61-379-7614, Fax: 82-61-379-7628, Kyc0923@jnu.ac.kr

Received 20 December 2004       Accepted 20 January 2005

Copyright©2005. The Korean Academy of Tuberculosis and Respiratory Diseases. All rights reserved.

Abstract

Microsatellites are short tandem repeated nucleotide sequences that are present throughout the human genome. Variations in the repeat number or a loss of heterozygosity around the microsatellites have been termed a microsatellite alteration (MA). A MA reflects the genetic instability caused by an impairment in the DNA mismatch repair system and is suggested to be a novel tumorigenic mechanism. A number of studies have reported that MA in the DNA extracted from the plasma occurs at varying frequencies among patients with a non-small cell lung carcinoma (NSCLC).
The genomic DNA from 9 subjects with a non-small cell lung cancer (squamous cell cancer 6, adenocarcinoma 2, non-small cell lung cancer1) and 9 age matched non-cancer control subjects (AMC: tuberculosis 3, other inflammatory lung disease 6) and 12 normal control subjects (NC) were extracted from the peripheral blood leukocytes and plasma. Three microsatellite loci were amplified with the primers targeting the Gene Bank sequence D21S1245, D3S1300, and D3S1234. MA in the form of an allelic loss or a band shift was examined with 6% polyacrylamide gel electrophoresis and silver staining.
None (0/12) of the NC subjects less than 40 years of age showed a MA in any of the three markers, while 88.9%(8/9) of the AMC above 40 showed a MA in at least one of the three markers (p<0.05). Sixty percent(6/10) of the control subjects with a smoking history showed a MA in one of the three markers, while 9.1%(1/11) of the control subjects without smoking history showed a MA (p<0.05). However, not only did 66.7%(6/9) of lung cancer patients show a MA in at least one of the three markers but so did 88.9%(8/21) of the AMC patients (p>0.05).
In conclusion, a MA in the D21S1245, D3S1300, and D3S1234 loci using DNA extracted from the plasma was detected in 66.7% of lung cancer while no MA was found in the young non-smoking control subjects. However, many of the non-cancer control subjects (aged smokers) also showed a MA, which compromised the specificity of the MA analysis as a screening test. Therefore, a further study with a larger sample size will be needed.

Keywords: Non-Small Cell Lung cancer, Microsatellite Alteration, Plasma DNA

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