Germline mutations in the E-cadherin and TP53 genes, but not in HPP1 or RUNX3 are associated with genetic predisposition for gastric cancer

Identification and characterization of a novel germ line p53 mutation in familial gastric cancer in the Japanese population

“…However, because of the relatively low frequency of gastric cancer in LFS families with the characteristics of both LFS and FGC are thought to be rare, and in fact, the case described above is the only one even reported (24). On the other hand, when our Japanese case is added to the previous two German and Portuguese cases (22,23), the number of FGC families with a germline p53 mutation that do not meet the clinical criteria for LFS rise to three. As regards frequency of the detection of FGC with a germline p53 mutation, according to the previous papers (22,23) and the present paper one FGC with a germline p53 mutation was found in 35 Japanese families with FGC, one among 34 German families with FGC, and one among 10 Portuguese families with FGC.…”

“…germline mutation is specific to a family with gastric cancer clustering. There have been three reports of FGC families in which a germline mutation of the p53 gene has been identified in Europe and Korea (22)(23)(24). One of the families meets the clinical criteria for LFS (24), but, the other two do not (22,23).…”

“…There have been three reports of FGC families in which a germline mutation of the p53 gene has been identified in Europe and Korea (22)(23)(24). One of the families meets the clinical criteria for LFS (24), but, the other two do not (22,23). LFS is a cancer predisposition syndrome associated with sarcoma, breast cancer, brain tumors, leukemia, adrenocortical carcinoma, melanoma, and other cancers, including gastric cancer (19)(20)(21).…”

“…Many somatic p53 mutations lead to a loss of p53 function and are detected in gastric cancer (17,18). 4 Germline p53 mutations are known to cause Li-Fraumeni syndrome (LFS) (19)(20)(21), and interestingly, germline p53 mutations have recently been found in European and Korean FGC patients (22)(23)(24). Since, to our knowledge only three FGC cases with a germline p53 mutation have been reported (22)(23)(24) and none have been in Japanese FGC patients, in the present study we investigated whether germline p53 mutations are responsible for FGC in a Japanese population by screening 35 Japanese FGC families for p53 germline mutations.…”

Relevance of MET activation and genetic alterations of KRAS and E-cadherin for cetuximab sensitivity of gastric cancer cell lines

“…Cross talk exists between EGFR and the cell adhesion molecule E-cadherin that modifies the function of both proteins. Mutations of the E-cadherin gene CDH1 are frequently observed in diffuse-type gastric cancer (Becker et al 1994;Keller et al 2004;Berx et al 1998;Oliveira et al 2003). Activation of EGFR is negatively influenced by normal E-cadherin-mediated cell adhesion (Qian et al 2004), and we have previously shown that somatic and germline CDH1 mutations are associated with enhanced EGFR activation (Bremm et al 2008;Mateus et al 2007).…”