Identification of tumor suppressor loci on the long arm of chromosome 5 in primary small cell lung cancers

Cho, Eun Song; Kim, Ho Guen; Cho, Chul Ho; Chang, Joon; Chung, Kyung Young; Kim, Young Sam; Park, Jae Min; Kim, Sung Kyu; Kim, Se Kyu

Abstract

BACKGROUND
Recent cytogenetic studies indicated that loss of the long arm of chromosome 5 is a frequent event in small cell lung cancer (SCLC), suggesting the presence of a tumor suppressor gene is its place. To map the precise tumor-suppressor loci on the chromosome arm for further positional cloning efforts, we tested 15 primary SCLCs.
METHODS
The DNAs extracted from paraffin-embedded tissue blocks with primary tumor and corresponding control tissue were investigated. Nineteen polymorphic microsatellite markers located in the long arm of chromosome 5 were used in the microsatellite analysis.
RESULTS
We found that ten (66.7%) of 15 tumors exhibited LOH in at least one of tested microsatellite markers. Two (13%) of 10 tumors exhibiting LOH lost a larger area in chromosome 5q. LOH was observed in five common deleted regions at 5q. Among those areas, LOH between 5q34-qter and 5q35.2-35.3 was most frequent (75%). LOH was also observed in more than 50% of the tumors at four at other regions, between 5q14-15 and 5q23-31, 5q31.1, 5q31.3-33.3, and 5q34-35. Three of 15 tumors exhibited shifted bands in at least one of the tested microsatellite markers. Shifted bands occurred in 2.5% (7 of 285) of the loci tested.
CONCLUSION
Our data demonstrated that at least five tumor-suppressor loci exist in the long arm of chromosome 5 and that they may play an important role in small cell lung cancer tumorigenesis.