Mutational analysis of <i>CASP1</i>, <i>2</i>, <i>3</i>, <i>4</i>, <i>5</i>, <i>6</i>, <i>7</i>, <i>8</i>, <i>9</i>, <i>10</i>, and <i>14</i> genes in gastrointestinal stromal tumors

다국어 초록 (Multilingual Abstract)

<P><B>Summary</B></P><P>Deregulation of apoptosis is one of the hallmarks of cancer, and inactivation of cancer cell apoptosis has been reported in many cancers. Caspases, the main executioners during apoptosis and inflammation, have been reported to harbor inactivating mutations in several cancers. The aim of this study was to explore whether <I>CASP1</I> to <I>10</I> and <I>14</I> genes that encode caspase 1 to 10 and 14 are somatically mutated in gastrointestinal stromal tumor. We analyzed the entire coding region and all splice sites of all 11 human <I>CASP</I> genes for the detection of somatic mutations in 22 gastrointestinal stromal tumors by a single strand conformation polymorphism assay. We found a recurrent <I>CASP4</I> mutation (c.1093C>G [p.L365V]) in 4 gastrointestinal stromal tumors, but there were no mutations in the other 10 <I>CASP</I>s. The <I>CASP4</I> mutation was a missense mutation and was predicted to substitute amino acids in the small protease subunit of caspase 4. Overall, the gastrointestinal stromal tumor tissues harbored a <I>CASP</I> mutation in 18.2% (4/22). Our data indicate that somatic mutation of the <I>CASP4</I> gene is common in gastrointestinal stromal tumor and suggest a possibility that <I>CASP4</I> mutation might lead to alteration of apoptotic or inflammatory function and contribute to the pathogenesis of some gastrointestinal stromal tumors.</P>