A novel germline mutation in the MET extracellular domain in a Korean patient with the diffuse type of familial gastric cancer

Presence of autocrine hepatocyte growth factor-Met signaling and its role in proliferation and migration of SNU-484 gastric cancer cell line

“…One of them is a P1009S mutation, which was localized in the juxtamembrane domain and showed transforming activity in nude mice. The other is a P791L mutation localized in the extracellular domain (Kim et al, 2003). Since the frequency of the mutation was quite low in both studies, it is obvious that Met mutation does not seem to play a major role in the development of gastric cancer unlike in papillary renal carcinomas.…”

“…Genetic analysis of human papillary renal carcinomas indicated that activating missense mutations in the met gene, which was found to be confined in tyrosine kinase domain, were causative in inherited and some sporadic papillary renal carcinomas (Schmidt et al, 1997). Whereas no mutation in the tyrosine kinase domain has been detected in primary gastric carcinomas or gastric cancer cell lines Yokozaki et al, 2000;Kim et al, 2003), two mutations in other parts of met have been identified in gastric cancer patients. One of them is a P1009S mutation, which was localized in the juxtamembrane domain and showed transforming activity in nude mice.…”

Familial gastric cancers with Li-Fraumeni Syndrome: A case repast

“…Although the incidence of gastric cancer has declined somewhat in recent years, it remains one of the most common cancers worldwide [1] , and is the most common cancer in East Asian countries such as Korea and Japan [2] . In terms of the genetics of gastric cancer, mutations in CDH1 (E-cadherin) have been associated with hereditary diffuse gastric cancer (HDGC).…”

“…Interestingly, the observed CDH1 germline mutations differ between Western and Asian countries; the mutation frequencies are higher in Western countries, with predominately truncating germline mutations observed, whereas only a few different missense mutations have been reported in Asian countries [6] . This ethnic difference and the low frequencies of CDH1 germline mutation in Asian populations prompted researchers to seek other susceptibility gene for Asian familial gastric cancer (FGC) [2,7] . We found a MET germline mutation in a FGC patient suffering from a diffuse type of gastric cancer [2] , and another group reported a MET germline mutation in a gastric cancer patient without detailed family history information [7] .…”

“…This ethnic difference and the low frequencies of CDH1 germline mutation in Asian populations prompted researchers to seek other susceptibility gene for Asian familial gastric cancer (FGC) [2,7] . We found a MET germline mutation in a FGC patient suffering from a diffuse type of gastric cancer [2] , and another group reported a MET germline mutation in a gastric cancer patient without detailed family history information [7] . These MET germline mutations were also found in Korean gastric cancer patients, but the overall MET mutation frequencies seem to be low (1% [7] and 5% [2] ), suggesting that while MET germline mutations may be causative in Korean or Asian gastric cancer patients, they likely do not play a major role in the development of FGC.…”