Polyclonal nature of diffuse proliferation of interstitial cells of Cajal in patients with familial and multiple gastrointestinal stromal tumours

Chen, H.; HIrota, S.; Isozaki, K.; Sun, H.; Ohashi, A.; Kinoshita, K.; O'Brien, P.; Kapusta, L.; Dardick, I.; Obayashi, T.; Okazaki, T.; Shinomura, Y.; Matsuzawa, Y.; Kitamura, Y.
December 2002
Gut;Dec2002, Vol. 51 Issue 6, p793
Academic Journal
Background: Diffuse proliferation of interstitial cells of Cajal (ICCs) in the myenteric plexus layer of the intestine has been described in patients with familial and multiple gastrointestinal stromal tumours (GISTs). However, it is not fully understood whether proliferation is polyclonal or monoclonal. Aims: To evaluate the clonal nature of diffuse ICC proliferation in familial and multiple GIST cases, we carried out clonal analysis using inactivation at the human androgen receptor (HUMARA) locus. Materials and methods: Diffuse ICC proliferation tissues from three female patients were microdissected using a laser capture microdissection (LCM) system. Normal intestinal mucosal tissues were also microdissected for polyclonal controls and GIST tissues for monoclonal controls from the same patients, and genomic DNA was extracted. After digestion by restriction enzyme Hhal, the HUMARA locus was amplified by a fluorescent polymerase chain reaction (PCR) procedure and the PCR products were analysed. Results: One case was uninformative because it was homozygous at the HUMARA locus. In the two other cases, PCR products from the diffuse ICC proliferation showed two alleles as well as those from normal intestinal mucosal tissues, indicating that ICC proliferation was polyclonal. In contrast, PCR products from associated GIST tissues showed only one allele, indicating that GISTs were monoclonal. Conclusion: The results suggested that diffuse ICC proliferation in familial and multiple GIST cases was non-neoplastic hyperplasia.


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