TY - JOUR
T1 - CDH1-related hereditary diffuse gastric cancer syndrome: Clinical variations and implications for counseling
AU - Kluijt, Irma
AU - Siemerink, Ester J. M.
AU - Ausems, Margreet G. E. M.
AU - van Os, Theo A. M.
AU - de Jong, Daphne
AU - Simões-Correia, Joana
AU - van Krieken, J. Han
AU - Ligtenberg, Marjolijn J.
AU - Figueiredo, Joana
AU - van Riel, Els
AU - Sijmons, Rolf H.
AU - Plukker, John T. M.
AU - van Hillegersberg, Richard
AU - Dekker, Evelien
AU - Oliveira, Carla
AU - Cats, Annemieke
AU - Hoogerbrugge, Nicoline
AU - Sijmons, RH
PY - 2012
Y1 - 2012
N2 - CDH1 mutation carriers have a strongly increased risk of developing gastric cancer (GC) and lobular breast cancer (LBC). Clinical data of GC cases and surgical and histological data of prophylactic gastrectomies and mastectomies of all 10 Dutch CDH1 mutation families were collected. In vitro functional assays were performed to analyze the nature of the newly found missense mutation c.1748T>G (p.Leu583Arg). Ten different CDH1 mutations were found. Functional assays gave strong arguments for the pathogenic nature of the p.Leu583Arg mutation. The pedigrees comprised 36 GC cases (mean age 40 years, range 2072 years) and one LBC case. Twenty-nine/37 carriers alive, aged 1861 years, underwent prophylactic gastrectomy. Invasive GC-foci and premalignant abnormalities were detected in 2 and 25 patients, respectively. In four patients GC/signetring cell (SRC) foci were diagnosed at preoperative gastroscopy. Long-standing presence of SRCs without progression to invasive carcinoma was shown in two others. Multifocal LBC/LCIS was found in the two prophylactic mastectomy specimens. Clefts of lip and/or palate (CL/P) were reported in seven individuals from three families. The age at onset and aggressiveness of GC is highly variable, which has to be included in counseling on planning prophylactic gastrectomies. The incidence of LBC is expected to increase and prophylactic mastectomy needs to be considered. The relationship between CL/P and CDH1 needs further study to inform future parents from hereditary diffuse gastric cancer (HDGC) families adequately
AB - CDH1 mutation carriers have a strongly increased risk of developing gastric cancer (GC) and lobular breast cancer (LBC). Clinical data of GC cases and surgical and histological data of prophylactic gastrectomies and mastectomies of all 10 Dutch CDH1 mutation families were collected. In vitro functional assays were performed to analyze the nature of the newly found missense mutation c.1748T>G (p.Leu583Arg). Ten different CDH1 mutations were found. Functional assays gave strong arguments for the pathogenic nature of the p.Leu583Arg mutation. The pedigrees comprised 36 GC cases (mean age 40 years, range 2072 years) and one LBC case. Twenty-nine/37 carriers alive, aged 1861 years, underwent prophylactic gastrectomy. Invasive GC-foci and premalignant abnormalities were detected in 2 and 25 patients, respectively. In four patients GC/signetring cell (SRC) foci were diagnosed at preoperative gastroscopy. Long-standing presence of SRCs without progression to invasive carcinoma was shown in two others. Multifocal LBC/LCIS was found in the two prophylactic mastectomy specimens. Clefts of lip and/or palate (CL/P) were reported in seven individuals from three families. The age at onset and aggressiveness of GC is highly variable, which has to be included in counseling on planning prophylactic gastrectomies. The incidence of LBC is expected to increase and prophylactic mastectomy needs to be considered. The relationship between CL/P and CDH1 needs further study to inform future parents from hereditary diffuse gastric cancer (HDGC) families adequately
U2 - https://doi.org/10.1002/ijc.26398
DO - https://doi.org/10.1002/ijc.26398
M3 - Article
C2 - 22020549
SN - 0020-7136
VL - 131
SP - 367
EP - 376
JO - International journal of cancer. Journal international du cancer
JF - International journal of cancer. Journal international du cancer
IS - 2
ER -