Mutations in exons 9 and 13 of KIT gene are rare events in gastrointestinal stromal turners - A study of 200 cases

Gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumors of the gastrointestinal tract, typically express the KF protein, Activatin g mutations in the juxtamembrane domain (exon 11) of the c-kit gene have be en shown in a subset of GISTs, These mutations lead into ligand-independent activation of the tyrosine kinase of c-kit, and have a transforming effect in vitro, Several groups have studied the clinical implication of the c-ki t mutation status of exon 11 in GISTs and a possible relationship between c -kit mutations and malignant behavior has been established. Recently, a 153 0ins6 mutation in exon 9 and missense mutations, 1945A>G in exon 13 of the c-kit gene were reported. The frequency and clinical importance of these fi ndings are unknown, In this study we evaluated 200 GISTs for the presence o f mutations in exons 9 and 13 of c-kit. Six cases revealed 1530ins6 mutatio n in exon 9 and two cases 1945A>G mutation in exon 13. All tumors with muta tions in exon 9 and 13 lacked mutations in exon 11 of c-kit. None of the an alyzed tumors had more than one type of c-Lit mutation. All but one of the eight tumors with mutations in exon 9 or 13 of the c-kit gene were histolog ically and clinically malignant. All four of six cases with exon 9 mutation of which location of primary tumor was known, were small intestinal, sugge sting that this type of mutation could preferentially occur in small intest inal tumors. Exon 9 and 13 mutations seem to be rare, and they cover only a small portion (8%) of the balance of GISTs that do not have mutations in e xon 11 of c-kit. This finding indicates that other genetic alterations may activate c-kit in GISTs, or that KIT is not activated by mutations in all c ases.