| A. Study criteria and E-cadherin mutation status | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Clinical criteria | No. families | No. affected families | Type of E-cadherin mutation | Predicted effect | ||||||
| 1. Two or more documented cases of DGC diagnosed before age 50 | 6 | 2 | 1 substitution 1 deletion | Premature stop-codon Frameshift | ||||||
| 1A. Two or more cases of GC, with at least one DGC before age 50 | 8 | 3 | 2 substitution 1 substitution | Premature stop-codon Alternative Splice site | ||||||
| 2A. Three or more cases of gastric cancer, diagnosed at any age, with at least one documented case of DGC | 4 | 1 | 1 substitution | Premature stop codon | ||||||
| 3. Isolated individual diagnosed with DGC at <45 y | 10 | 2 | 1 substitution 1 deletion | Missense change Frameshift | ||||||
| 4. Isolated individual diagnosed with both DGC and LBC | 1 | 1 | 1 substitution | Loss of start codon | ||||||
| 5. One family member diagnosed with DGC and another with LBC | 1 | 0 | — | — | ||||||
| 6. One family member diagnosed with DGC and another with colon cancer | 1 | 0 | — | — | ||||||
| B. Details of the gastric cancer families in the study and mutations detected | ||||||||||
| Case/criterion | Members reported with gastric cancer/ confirmed DGC | Age range | Members reported with breast cancer/ confirmed LBC | Gene location | Nucleotide change | |||||
| F1/1 | 8/2 | 25-67 | 0 | Exon 7 | c.1003C>T | |||||
| F2/1 | 10/2 | 35-87 | 2/1 | Exon 14 | c.2276del | |||||
| F3/1A | 5/1 | 31-55 | 0 | Exon 7 | c. 1003C>T | |||||
| F4/1A | 4/1 | 21-75 | 0 | Exon 13 | c.2161C>G | |||||
| F5/1A | 4/1 | 30-54 | 2/0 | Exon 12 | c.1792C>T | |||||
| F6/2A | 3/1 | 24-52 | 3/2* | Exon 3 | c.187C>T | |||||
| C5/3 | 1/1 | 27 | 0 | Exon 8 | c.1063del | |||||
| C6/3 | 1/1 | 27 | 0 | Exon 9 | c.1285C>T | |||||
| C7/4 | 1/1 | 73 | 1/1 | Exon 1 | c.3G>C | |||||
↵* One individual had mixed lobular and ductal carcinoma of the breast with signet ring cells.