We screened a series of 66 young gastric cancer probands for germline CDH1 mutations, and two novel missense alterations together with an intronic variant were identified.
We hypothesized that CDH1 genomic rearrangements would be found in HDGC and identified 160 families with either two gastric cancers in first-degree relatives and with at least one diffuse gastric cancer (DGC) diagnosed before age 50, or three or more DGC in close relatives diagnosed at any age.
We have shown that germline CDH1 mutations are associated with early onset of bilateral LCIS with or without ILC in women without a family history of gastric cancer.
We detected the epidermal growth factor receptor L858R, MSH2 R929* and telomerase reverse transcriptase amplification in the lung cancer specimen; CDH1 c.1320+1G>T mutation in the gastric cancer (GC) specimen; and MLH1 c.1896+5G>A germline mutation in the lung and GC specimens by 450 cancer-related gene mutations detection using next-generation sequencing technology.
Using polymerase chain reaction (PCR)/single-strand conformation polymorphism (SSCP)/sequencing, we screened 32 Portuguese families with a history of gastric cancer and 23 patients with early onset gastric cancer for CDH1 germline mutations.
TP53 mutation, allelic deletion of the APC gene and nuclear staining of β-catenin are frequently detected in the intestinal phenotype of GC, whereas CDH1 gene mutation, microsatellite instability and DNA hypermethylation of MLH1 are common events in the gastric phenotype of GC.
To our knowledge, this is the first Korean case of presymptomatic detection of CDH1 mutation, and it highlights the importance of genetic screening for individuals with a family history of GC, especially in high-risk geographical areas.
To identify genetic variants that affect risk for gastric cancer, we collected blood samples from 28 patients with hereditary diffuse gastric cancer (HDGC) not associated with mutations in CDH1 and performed whole-exome sequence analysis.
This study evaluated the effect of PTG on health-related quality of life (HRQL) in asymptomatic individuals with identified CDH1 mutations at high risk for gastric cancer.
This data could open new approaches in the gastric cancer prevention test; before proposing a proband candidate for the CDH1 genetic screening, geographic variability, alongside the family history should be considered.
This case highlights the importance of recognition of the HDGC syndrome and of testing for CDH1 germline mutations in young individuals with diffuse gastric cancer without a family history of the disease.
Thirty-six percent (5 of 14) of the families with a documented DGC diagnosed before the age of 50 and other cases of gastric cancer carried CDH1 germ line mutations.
These results suggest that the ATCTG and CTTTG CDH1 haplotypes may be associated with an increased risk and decreased risk, respectively, of GC in the Japanese population.