MOLECULAR ANALYSIS OF THE ADENOMATOUS POLYPOSIS-COLI GENE IN SARCOMAS, HEMATOLOGICAL MALIGNANCIES AND NONCOLONIC, NEOPLASTIC TISSUES

Somatic mutations of the adenomatous polyposis coli (APC) gene have be en frequently found in sporadic colorectal tumors, and the frequency o f such mutations remain constant as tumors progress from benign adenom as to malignant cancers. Thus the mutations of the APC gene may have a major role in the early development of sporadic colorectal tumors. Wh ether inactivation of the APC gene accounts for other types of primary tumors is still being investigated. We investigated for APC mutations within the mutation cluster region (a 684-bp region containing most o f the mutations found in colorectal tumors) in 317 samples from a wide variety of human malignant and premalignant tissues, including 40 lun g cancers, 47 renal cell carcinomas, 41 osteosarcomas and 21 other typ es of sarcomas, 45 acute lymphoid leukemias/lymphomas, 33 acute myeloi d leukemias, 27 myelodysplastic syndrome samples, and 20 chronic colit is (ulcerative colitis and Crohn's disease) associated cancers and dys plasias, and 43 human malignant cell lines. We used single-strand conf ormation polymorphism assay following polymerase chain reaction. Sampl es with abnormal assay results were reamplified and analyzed by the di rect DNA sequencing method. We detected a total of two cases with a ba se substitution. A silent mutation was detected in a case of myelodysp lastic syndrome, and a novel nonsense mutation was discovered in a col orectal cancer cell line, SW837. In summary, we did not detect any fun ctional mutations of the APC gene in a wide variety of tumors except f or a colon cancer cell line, suggesting that alterations of the APC ge ne do not have a major role in the development of lung and renal cance rs, various types of sarcomas, or hematological malignancies.