Hereditary Diffuse Gastric and Lobular Breast Cancer Syndrome
Hereditary Diffuse Gastric and Lobular Breast Cancer Syndrome
Testing for CDH1 germline mutations was carried out in 165 unrelated Ile-de-France index cases (Table 1). Eighteen (11%) were mutation carriers (Table 2). Of these, 11 had a personal or family history that fulfilled the 2010 HDGC criteria: one came from a family with three cases of DGC; five came from families with two cases of DGC, one of them below age 50; three had sporadic DGC below age 40; and two had a personal or family history of LBC and DGC, with one of the cancers diagnosed before age 50. The seven remaining cases did not meet the HDGC criteria: three had sporadic bilateral LBC below age 50; three came from families with two cases of DGC after age 50; and one had sporadic DGC after age 40. There were 16 different CDH1 gene mutations in the 18 index cases. Fourteen were point mutations or small insertions/deletions detected by sequencing, and two were large deletions detected by MLPA/qPCR. Nine of the 16 gene mutations have never been reported in the literature.
Three of our cases, IC1, IC2 and VJ3, were women with a personal history that consisted initially of bilateral LBC below age 50. Family history was negative for DGC in first- and second-degree relatives, and they therefore did not meet the HDGC criteria at this stage. They all tested negative for mutations in BRCA1 and BRCA2. Cases IC1 and IC2 were only tested for CDH1 after subsequently developing symptomatic DGC and, as a result, meeting these criteria. Conversely, VJ3 had CDH1 testing shortly after the physician in charge had received the negative BRCA1/2 results. Upper gastrointestinal endoscopy with multiple biopsies followed, but no foci of cancer were found. She was nevertheless offered prophylactic gastrectomy, and the pathologist diagnosed invasive pT1N0 DGC.
Results
Testing for CDH1 germline mutations was carried out in 165 unrelated Ile-de-France index cases (Table 1). Eighteen (11%) were mutation carriers (Table 2). Of these, 11 had a personal or family history that fulfilled the 2010 HDGC criteria: one came from a family with three cases of DGC; five came from families with two cases of DGC, one of them below age 50; three had sporadic DGC below age 40; and two had a personal or family history of LBC and DGC, with one of the cancers diagnosed before age 50. The seven remaining cases did not meet the HDGC criteria: three had sporadic bilateral LBC below age 50; three came from families with two cases of DGC after age 50; and one had sporadic DGC after age 40. There were 16 different CDH1 gene mutations in the 18 index cases. Fourteen were point mutations or small insertions/deletions detected by sequencing, and two were large deletions detected by MLPA/qPCR. Nine of the 16 gene mutations have never been reported in the literature.
Three of our cases, IC1, IC2 and VJ3, were women with a personal history that consisted initially of bilateral LBC below age 50. Family history was negative for DGC in first- and second-degree relatives, and they therefore did not meet the HDGC criteria at this stage. They all tested negative for mutations in BRCA1 and BRCA2. Cases IC1 and IC2 were only tested for CDH1 after subsequently developing symptomatic DGC and, as a result, meeting these criteria. Conversely, VJ3 had CDH1 testing shortly after the physician in charge had received the negative BRCA1/2 results. Upper gastrointestinal endoscopy with multiple biopsies followed, but no foci of cancer were found. She was nevertheless offered prophylactic gastrectomy, and the pathologist diagnosed invasive pT1N0 DGC.
Source...