A novel mutation in the E-cadherin gene in the first family with hereditary diffuse gastric cancer reported in Spain

Rodríguez‐Sanjuán, Juan Carlos; Fontalba, Ana; Mayorga, Marta; Bordin, Maria Cristina; Hyland, Sarah J; Trugeda, S.; Arroyo-García, Rosa; Gómez-Fleitas, Manuel; Fernández, Fidel Fernández; Caldas, Carlos; Fernández-Luna, José L.

doi:10.1016/j.ejso.2006.06.006

Cited by 23 publications

(4 citation statements)

References 10 publications

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“…It is not clear whether the proband's personal history of Hodgkin's lymphoma is related to her germline CDH1 mutation. There has been one previous report of a gastric lymphoma in the setting of Helicobacter pylori infection reported in a kindred with a germline CDH1 mutation (16); however, there have been no previously reported cases of Hodgkin's lymphoma. The risk of a second neoplasm following the treatment for Hodgkin's lymphoma is significant; as high as 5% for all survivors (17), and most frequently include breast cancer, thyroid cancer, and bone or soft tissue sarcoma, although gastric cancer has also been reported (17, 18).…”

Section: Discussionmentioning

confidence: 98%

De novo CDH1 mutation in a family presenting with early‐onset diffuse gastric cancer

Shah

Salo‐Mullen²,

Stadler

et al. 2011

Clinical Genetics

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In this report, we describe the first concluded case of a de novo germline mutation in CDH1 in a hereditary diffuse gastric cancer (HDGC) kindred. The incident case was a woman with a personal history of Hodgkin's lymphoma and diffuse gastric cancer, who was then confirmed to have a CDH1 mutation (c.1792 C>T (R598X)). The patient's mother was found to have the same CDH1 germline mutation; however, neither maternal grandparent was found to carry the mutation, thus leading to a conclusion that the proband's mother's mutation is of de novo origin. 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.

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Section: Discussionmentioning

confidence: 98%

De novo CDH1 mutation in a family presenting with early‐onset diffuse gastric cancer

Shah

Salo‐Mullen²,

Stadler

et al. 2011

Clinical Genetics

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“…Truncating alleles of CDH1 were first identified in Maori (indigenous New Zealander) families in which many members had died from DGC very young, typically at age 14–40 years . Inactivating alleles of CDH1 have since been identified in HDGC families from many different ethnic backgrounds ; however, for the majority of HDGC families the genetic cause remains unknown.…”

Section: Introductionmentioning

confidence: 99%

An α‐E‐catenin (CTNNA1) mutation in hereditary diffuse gastric cancer

Majewski

Kluijt

Cats

et al. 2013

The Journal of Pathology

199

136

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Diffuse gastric cancers typically present as late-stage tumours and, as a result, the 5 year survival rate is poor. Some gastric cancers are hereditary and these tend to be of the diffuse type; 30-40% of hereditary diffuse gastric cancers (HDGCs) can be explained by defective germline alleles of E-cadherin (CDH1), but for the remaining families the factors driving susceptibility remain unknown. We had access to a large HDGC pedigree with no obvious mutation in CDH1, and applied exome sequencing to identify new genes involved in gastric cancer. We identified a germline truncating allele of α-E-catenin (CTNNA1) that was present in two family members with invasive diffuse gastric cancer and four in which intramucosal signet ring cells were detected as part of endoscopic surveillance. The remaining CTNNA1 allele was silenced in the two diffuse gastric cancers from the family that were available for screening, and this was also true for signet ring cells identified in endoscopic biopsies. Since α-E-catenin functions in the same complex as E-cadherin, our results call attention to the broader signalling network surrounding these proteins in HDGC. We also detected somatic mutations in one tumour and found substantial overlap with genes mutated in sporadic gastric cancer, including PIK3CA, ARID1A, MED12 and MED23.

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“…8 Subsequently, different germline mutations have been identified in families with different ethnic backgrounds worldwide. [9][10][11][12][13][14] The lifetime risk (LTR) for GC in HDGC kindreds is high and is estimated >80%. 7 Because of this high risk and the restricted value of current surveillance modalities, prophylactic gastrectomy is recommended as the treatment of choice in CDH1 mutation carriers in preventing advanced GC.…”

mentioning

confidence: 99%

CDH1‐related hereditary diffuse gastric cancer syndrome: Clinical variations and implications for counseling

Kluijt¹,

Siemerink

Ausems

et al. 2011

Intl Journal of Cancer

117

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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 20–72 years) and one LBC case. Twenty‐nine/37 carriers alive, aged 18–61 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.

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A novel mutation in the E-cadherin gene in the first family with hereditary diffuse gastric cancer reported in Spain

Cited by 23 publications

References 10 publications

De novo CDH1 mutation in a family presenting with early‐onset diffuse gastric cancer

De novo CDH1 mutation in a family presenting with early‐onset diffuse gastric cancer

An α‐E‐catenin (CTNNA1) mutation in hereditary diffuse gastric cancer

CDH1‐related hereditary diffuse gastric cancer syndrome: Clinical variations and implications for counseling

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