Chromosome 22q alterations and expression of the NF2 gene product, merlin, in gastrointestinal stromal tumors☆
Section snippets
Tumor specimens
A total of 42 GISTs were collected from the files of the Department of Pathology, Haartman Institute, University of Helsinki (Table 1). Matching normal tissue samples were available from 29 patients. The study included 26 male and 16 female patients, with a median age of 64 years at the time of diagnosis (range, 41 to 87 years). Thirty-one tumors were located in the stomach, 10 tumors were in the small intestine (9 in the jejunum and 1 in the ileum), and 1 tumor was in the rectum. Tumor
Results
Tumor material consisted of 42 GISTs, the demographic data and clinical features of which are given in Table 1. Twelve highly polymorphic microsatellite markers that span the long arm of chromosome 22 and 2 complementary techniques were used for detection of LOH (Fig 2). Overall, 69% of the tumors showed LOH with at least 1 of the 22q markers. Allele losses were compared with tumor mitotic activity, the most commonly used prognostic marker for this tumor type. Of the 42 tumors, 17 (40%) showed
Discussion
This study has demonstrated that LOH at 22q is a frequent event in GISTs, with an overall frequency close to 70%. In GISTs with high mitotic activity, an indicator of potential malignancy, allelic losses occurred in nearly 90% of the tumors, whereas approximately half of the tumors with low mitotic activity exhibited LOH. A 4.6-fold risk of recurrence or disease-related death was observed in cases with 22q LOH at all informative sites as compared with those with no LOH. These data suggest the
Acknowledgements
The authors thank Tuula Niilola and Tuula Suitiala for skillful technical assistance and Dr. Timo Partanen and Anneli Ojajärvi for their expert statistical analyses.
References (23)
- et al.
Gastrointestinal stromal tumorsRecent advances in understanding of their biology
Hum Pathol
(1999) - et al.
Different patterns of DNA copy number changes in gastrointestinal stromal tumors, leiomyomas, and schwannomas
Hum Pathol
(1998) - et al.
Stem cell factor is encoded at the Sl locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor
Cell
(1990) - et al.
Loss of 14q and 22q in gastrointestinal stromal tumors (pacemaker cell tumors)
Cancer Genet Cytogenet
(2000) - et al.
Gastrointestinal stromal tumor, uncommitted type, with monosomies 14 and 22 as the only chromosomal abnormalities
Cancer Genet Cytogenet
(1998) - et al.
A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor
Cell
(1993) Molecular insights into neurofibromatosis 2
Neurobiol Dis
(1997)- et al.
Gastrointestinal stromal tumors—Definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis
Virchows Arch
(2001) - et al.
CD117A sensitive marker for gastrointestinal stromal tumors that is more specific than CD34
Mod Pathol
(1998) - et al.
Gastrointestinal pacemaker cell tumor (GIPACT)Gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal
Am J Pathol
(1998)
Human proto-oncogene c-kitA new cell surface receptor tyrosine kinase for an unidentified ligand
EMBO J
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Molecular and clinicopathologic characterization of intravenous leiomyomatosis
2020, Modern PathologyGenomic index predicts clinical outcome of intermediate-risk gastrointestinal stromal tumours, providing a new inclusion criterion for imatinib adjuvant therapy
2015, European Journal of CancerCitation Excerpt :In this study, high GI values were not found, however, to be more often associated with KIT exon 11 mutations than with other mutations (Table 3 and data not shown). Apart from the impact of mutations, a few gene abnormalities due the frequent loss of 1p and 22q loci have also been related to poorer prognosis [38–40]. More recently we highlighted genome complexity as a strong predictor of GIST clinical outcome [28], unveiling a crucial role of genome profiling and genetic changes as potent predictive factors for GIST.
Monitoring of loss of heterozygosity in serum microsatellite DNA among patients with gastrointestinal stromal tumors indicates tumor recurrence
2011, Journal of Surgical ResearchCitation Excerpt :The selection of the markers was based on the latest literature and our last studies [12, 14]. Hence, five markers on chromosome 22 were derived from a study on 42 GISTs, which associated the pathogenesis of GIST with the neurofibromatosis gene NF2 [10]. The other markers showed LOH in relevant regions in different carcinoma and sarcoma studies.
Genetic aberrations in soft tissue leiomyosarcoma
2009, Cancer LettersCitation Excerpt :The frequent deletion of chromosome 22 reported in this study was not found in the larger studies discussed in the above paragraph. An interesting note is that monosomy of chromosome 22q has been reported as a frequent event in GIST [18]. Therefore, it is possible that some of these tumors classified as leiomyosarcoma in that study may actually be GIST if they were re-evaluated.
High incidence of microscopic gastrointestinal stromal tumors in the stomach
2006, Human PathologyClinical and therapeutical management of gastrointestinal stromal tumours (GIST)
2006, Medicina Clinica
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Supported by grants from The Finnish Cancer Organization, Helsinki University Central Hospital, The Sigrid Juselius Foundation, Luise and Henrik Kuningas Foundation, and the Academy of Finland.