Frequency of TPR-MET rearrangement in patients with gastric carcinoma and in first-degree relatives

BACKGROUND, The activation of the c-met protooncogene through a rearrangeme nt has been detected previously in gastric carcinoma tissue and precancerou s lesions. In the current study the authors analyzed the rearrangement of T PR-MET in gastric carcinoma patients and in first-degree relatives to evalu ate the potential role and timepoint of this genetic alteration in the proc ess of gastric carcinogenesis and its potential value in identifying those individuals with an increased risk of developing gastric carcinoma. METHODS. The presence of TPR-MET mRNA was determined in gastric tissue from 19 patients with gastric carcinoma and in the gastric mucosa of 18 first-d egree relatives without gastric carcinoma and in the gastric mucosa of 18 f irst-degree relatives without gastric carcinoma using a nested reverse tran scriptase-polymerase chain reaction (RT-PCR) and Southern blot analysis. A 205-base pair (bp) cDNA fragment and a 70-bp cDNA fragment spanning the bre akpoint were amplified by nested PCR. Amplification products were hybridize d with an oligonucleotide labeled at the 3'-end with DIG-11-dUTP spanning t he breakpoint using Southern blot analysis. The MNNG-HOS cell line served a s a positive control. RESULTS. TPR-MET mRNA was detected in nine gastric carcinoma patients (47%) . Among these patients, TPR-MET mRNA was present in the both tumor and tumo r free tissues in 5 patients (26%), in the tumor tissue only in 2 patients (11%), and in the tumor free gastric mucosa only in 2 patients (11%). It is interesting to note that TPR-MET rearrangement also was detected in the ga stric corpus mucosa of 1 first-degree relative (6%), but in none of the con trol subjects. CONCLUSIONS, The data from the current study indicate that TPR-MET activati on may be an early event in gastric carcinogenesis and may be useful for th e identification of individuals with an increased risk of developing gastri c carcinoma. Cancer 2000;88:1801-6. (C) 2000 American Cancer Society.