| 研究実績の概要 |
The prognosis of patients with gastric carcinomas at an advanced stage still remains dismal and therefore novel therapeutic modalities are urgently needed. The aim of the present study was to determine the amplification status of 26 genes, which are frequently amplified in solid cancers, in advanced gastric cancers.
A total of 93 formalin-fixed and paraffin-embedded advanced gastric cancer tissues were examined by multiple ligation-dependent probe amplification (MLPA), and 32 cases with ‘gain’ or ‘amplified’ status of 16 genes were further examined for the respective gene amplification by fluorescence in situ hybridization (FISH). The frequencies of gene amplifications in advanced gastric cancers as assessed by these combined methods were as follows: ERBB2 (13 cases, 14.0%), FGFR2 (7 cases, 7.5%), MYC (7 cases, 7.5%), TOP2A (7 cases, 7.5%), MET (4 cases, 4.3%), MDM2 (4 cases, 4.3%), CCND1 (3 cases, 3.2%), FGF10 (2 cases, 3.2%), and EGFR (one case, 1.1%). Amplification of the RTK genes occurred in a mutually exclusive manner except for one tumor in which ERBB2 and FGFR2 were both amplified but in different cancer cells. Thus if a common tyrosine kinase inhibitor to the four RTKs were available, 24 of 93 (25.8%) cases of advanced gastric cancer would potentially be susceptible to that agent.
In conclusion, combination of MLPA and FISH analysis is a feasible approach for obtaining the semi-comprehensive genetic information that is necessary for personalized molecular targeted therapy.
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