A number of genetic and molecular alterations have been identified in lung cancer cells and thought to be important during the process of carcinogenesis. Several allelotyping studies of lung carcinoma indicate frequent losses at chromosome 5q, suggesting the presence of tumor suppressor genes in its place. Pulmonary large cell neuroendocrine carcinoma (LCNEC) is high-grade malignant neuroendocrine tumor. But the data on genetic changes of LCNEC are so limited. Therefore, to map the precise tumor suppressor loci on the chromosome 5q for further positional cloning efforts, we tested 13 surgically resected LCNEC specimens.
The DNAs extracted from paraffin-embedded tissue blocks with LCNEC and corresponding normal tissues were investigated. Nineteen polymorphic microsatellite markers located in chromosome 5q were used for analysis. Polymerase chain reaction was performed and loss of heterozygosity (LOH) was evaluated by the gel electrophoresis.
We found that all of 13 tumors exhibited LOH in at least one of tested microsatellite markers from D5S118 to D5S498. LOH was observed in five common deleted regions at 5q. The frequencies of LOH between D5S107 and D5S409, region of 5q11.2-13.3 and 5q14-15, were 91.7%. The frequencies of LOH between IL-9 and D5S210, region of 5q22.3-32 and 5q31.3-33.3, were 84.6%. The frequencies of LOH at D5S209, D5S400 and D5S429, each located in the region of 5q31.1-33.3, 5q34-35 and 5q34-qter, were 53.8%, 85.7%, and 63.6% respectively.
Our data suggest the presence of at least 5 tumor suppressor loci on 5q in LCNEC.
We think that more effort is needed to find tumor suppressor genes through the 5 putative tumor suppressor loci in LCNEC. It may contribute to understanding the pathogenesis of LCNEC.
S. Kang, None.