title: Allelic loss of 14q and 22q, NF2 mutation, and genetic instability occur independently of c-kit mutation in gastrointestinal stromal tumor.
abstract: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. Since c-kit mutation occurs only in one-third of GIST, there might be other molecular mechanisms. Loss of heterozygosity (LOH), microsatellite instability (MSI) and NF2 gene mutation were investigated in 22 GISTs (9 low-risk and 13 high-risk tumors). LOH and MSI were evaluated using 41 markers on 21 chromosomal arms, and NF2 gene mutation was examined by PCR-SSCP. High frequency of LOH was observed on 14q (9 / 19, 47%), and 22q (17 / 22, 77%). The frequencies were similar in low-risk and high-risk tumors, and were unrelated with gastric or intestinal origin. Two other abnormalities, additional LOH on other chromosomes and MSI at more than two loci, were characteristic of the high-risk tumors (P < 0.05). NF2 gene mutation was identified in two cases showing 22q-LOH (8 bp deletion on the splice donor site of exon 7, and 1 bp insertion at position 432 of exon 4, which resulted in nonsense mutation). There was no significant correlation between these results and c-kit gene mutation, which was observed in 8 of 22 tumors. Suppressor genes on 14q and 22q may be involved, independently of c-kit gene mutation, in the development of GIST. NF2 contributes as a tumor suppressor in a small subset of GIST. These abnormalities are presumably followed by increased genetic instability.
authors: Department of Pathology, Jichi Medical School, Minami-Kawachi-machi, Kawachi, Tochigi 329-0498, Japan. mfukayama-tky@umin.ac.jp
authors: T
authors: T
authors: Fukasawa
authors: J M
authors: JM
authors: Chong
authors: S
authors: S
authors: Sakurai
authors: N
authors: N
authors: Koshiishi
authors: R
authors: R
authors: Ikeno
authors: A
authors: A
authors: Tanaka
authors: Y
authors: Y
authors: Matsumoto
authors: Y
authors: Y
authors: Hayashi
authors: M
authors: M
authors: Koike
authors: M
authors: M
authors: Fukayama
mesh_terms: D000328:Adult; D000368:Aged; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14; D002892:Chromosomes, Human, Pair 22; D005091:Exons; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000235:genetics*; D016515:Genes, Neurofibromatosis 2; D005819:Genetic Markers; D006801:Humans; D007414:Intestinal Neoplasms / Q000235:genetics; D019656:Loss of Heterozygosity; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D018895:Microsatellite Repeats; D008875:Middle Aged; D020125:Mutation, Missense; D025581:Neurofibromin 2; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics
chemical_list: D005819:Genetic Markers; D008565:Membrane Proteins; D025581:Neurofibromin 2; D019009:Proto-Oncogene Proteins c-kit