Yonsei Med J.  2002 Apr;43(2):145-151. 10.3349/ymj.2002.43.2.145.

Identification of Tumor Suppressor Loci on the Long Arm of Chromosome 4 in Primary Small Cell Lung Cancers

Affiliations
  • 1Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
  • 2Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul, Korea.
  • 3Department of Cardiovascular and Thoracic Surgery, Yonsei University College of Medicine, Seoul, Korea.
  • 4Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
  • 5Institute of Chest Diseases, Yonsei University College of Medicine, Seoul, Korea.
  • 6Cancer Metastasis Research Center, Yonsei University College of Medicine, Seoul, Korea.

Abstract

Recent cytogenetic studies have indicated that loss of the long arm of chromosome 4 is a frequent event in small cell lung cancer (SCLC), which suggests the presence of tumor suppressor genes there. To precisely map tumor-suppressor loci on chromosome 4q for further positional cloning efforts, we tested 15 primary SCLCs. Forty two polymorphic microsatellite markers located on chromosome 4q were used in the microsatellite analysis. We found that 12 (80%) of the 15 tumors exhibited loss of heterozygosity (LOH) in at least one of the tested microsatellite markers, and that 3 (25%) of these 12 tumors exhibited a larger area of deletion on chromosome 4q. Frequent LOH, defined as occurring in more than 50% of the tumors, was observed in five commonly deleted regions on 4q, namely 4q24, 4q27-28.3, 4q33, 4q34.1, and 4q34.3-35.2. Of these 5, LOH at 4q33 was the most frequent (61.5%). Six (40%) of the 15 tumors exhibited shifted bands in at least one of the tested microsatellite markers. Shifted bands occurred in 3.7% (23 of 630) of the loci tested. Our data demonstrated that at least five tumor-suppressor loci exist on the long arm of chromosome 4 and that they may play an important role in the development and progression of primary small cell lung cancer tumorigenesis.

Keyword

Small cell lung cancer; chromosome 4; LOH; tumor suppressor

MeSH Terms

Carcinoma, Small Cell/*genetics
*Chromosome Mapping
Chromosomes, Human, Pair 4/*genetics
*Genes, Tumor Suppressor
Human
Loss of Heterozygosity
Lung Neoplasms/*genetics
Microsatellite Repeats
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