1. ¹Center for Human Genetics, Katholieke Universiteit Leuven, Belgium
2. ²Laboratory for Morphology and Molecular Pathology, Katholieke Universiteit Leuven, Belgium
3. ³Department of Surgery, Katholieke Universiteit Leuven, Belgium
4. ⁴Stichting PAMM, Catharinaziekenhuis, Eindhoven, the Netherlands
5. ⁵Department of Soft Tissue Pathology, Armed Forces Institute of Pathology, Washington, DC

Correspondence: Maria Debiec-Rychter, Center for Human Genetics, Katholieke Universiteit Leuven, O & N Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium. e-mail: maria.debiec-rychter@med.kuleuven.ac.be; fax: 32-16-346063

Accepted 22 March 2002.

Abstract

Gastrointestinal stromal tumors (GISTs) with neurogenic differentiation, also referred to as "gastrointestinal autonomic nerve tumors (GANTs)," form an ultrastructurally distinctive subgroup of mesenchymal neoplasms of gastrointestinal tract. Cytogenetic and molecular data of these tumors are limited. In the current study, c-KIT gene sequenc-ing analysis, comparative genomic hybridization (CGH), and interphase fluorescence in situ hybrid- ization (FISH) analysis, utilizing chromosome 14- and 22-specific probes, were performed on five primary ultrastructurally confirmed GANTs. FISH and CGH analysis revealed loss of a whole or part of chromosome 14q in two tumors and of chromo- some 22q, with the common overlapping area of loss at q13, in all five tumors evaluated. c-KIT mu- tations were found in all cases; three tumors carried point mutation and/or deletions of exon 11, and in two tumors, insertion in exon 9 was found. These findings suggest that accumulated genetic changes contribute to the pathogenesis of GANTs and that 22q13 loss may be a characteristic feature of these tumors.