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 rearrangement has been detected previously in gastric carcinoma tissue and precancerous lesions. In the current study the authors analyzed the rearrangement of TPR-MET in gastric carcinoma patients and in first-degree relatives to evaluate the potential role and timepoint of this genetic alteration in the process 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-degree relatives without gastric carcinoma and in the gastric mucosa of 18 first-degree relatives without gastric carcinoma using a nested reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blot analysis. A 205-base pair (bp) cDNA fragment and a 70-bp cDNA fragment spanning the breakpoint were amplified by nested PCR. Amplification products were hybridized with an oligonucleotide labeled at the 3'-end with DIG-11-dUTP spanning the breakpoint using Southern blot analysis. The MNNG-HOS cell line served as 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 tumor 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 gastric corpus mucosa of 1 first-degree relative (6%), but in none of the control subjects.


CONCLUSIONS
The data from the current study indicate that TPR-MET activation may be an early event in gastric carcinogenesis and may be useful for the identification of individuals with an increased risk of developing gastric carcinoma.
Yu
J
J
Medical Department I, Gastroenterology, Hematology and Oncology, Technical University Hospital, Dresden, Germany.
Miehlke
S
S
Ebert
M P
MP
Hoffmann
J
J
Breidert
M
M
Alpen
B
B
Starzynska
T
T
Stolte Prof
M
M
Malfertheiner
P
P
Bayerdörffer
E
E
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D002471:Cell Transformation, Neoplastic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D006801:Humans; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010375:Pedigree; D012333:RNA, Messenger / Q000235:genetics; D018570:Risk Assessment; D013274:Stomach Neoplasms / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology
D014408:Biomarkers, Tumor; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger