Lobular carcinoma in situ of the breast is not caused by constitutional mutations in the E-cadherin gene

Rahman, Nazneen; Stone, Joanne; Coleman, Gary D.; Gusterson, Barry A.; Seal, Shubhendu; Marossy, A; Lakhani, Sunil R.; Ward, Ann; Nash, A. G.; McKinna, A; A'Hern, R.; Stratton, M.R.; Houlston, Richard S.

doi:10.1054/bjoc.1999.0965

Cited by 32 publications

(22 citation statements)

References 18 publications

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“…However, in this small cohort, a positive family history was not clearly defined either for degree of relation or number of family members with breast cancer. The search for CDH1 germline mutations in a series of 65 LCIS patients also yielded negative results 17. One study has proposed that the CDH1 missense mutation 1774G→A (A592T) is a risk factor for comedo-type carcinoma, a pathological variant of ductal carcinoma in situ 14.…”

Section: Discussionmentioning

confidence: 99%

Germline E-cadherin mutations in familial lobular breast cancer

Masciari

Larsson

Senz

et al. 2007

Journal of Medical Genetics

163

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Background: The cell surface glycoprotein E-cadherin (CDH1) is a key regulator of adhesive properties in epithelial cells. Germline mutations in CDH1 are well established as the defects underlying hereditary diffuse gastric cancer (HDGC) syndrome, and an increased risk of lobular breast cancer (LBC) has been described in HDGC kindreds. However, germline CDH1 mutations have not been described in patients with LBC in non-HDGC families. This study aimed to investigate the frequency of germline CDH1 mutations in patients with LBC with early onset disease or family histories of breast cancer without DGC. Methods: Germline DNA was analysed in 23 women with invasive lobular or mixed ductal and lobular breast cancers who had at least one close relative with breast cancer or had themselves been diagnosed before the age of 45 years, had tested negative for a germline BRCA1 or BRCA2 mutation, and reported no personal or family history of diffuse gastric cancer. The full coding sequence of CDH1 including splice junctions was amplified using PCR and screened for mutations using DHPLC and sequencing. Results: A novel germline CDH1 truncating mutation in the extracellular portion of the protein (517insA) was identified in one woman who had LBC at the age of 42 years and a first degree relative with invasive LBC. Conclusions: Germline CDH1 mutations can be associated with invasive LBC in the absence of diffuse gastric cancer. The finding, if confirmed, may have implications for management of individuals at risk for this breast cancer subtype. Clarification of the cancer risks in the syndrome is essential.

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Section: Discussionmentioning

confidence: 99%

Germline E-cadherin mutations in familial lobular breast cancer

Masciari

Larsson

Senz

et al. 2007

Journal of Medical Genetics

163

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“…Germline mutations of the E-cadherin gene have been found in families susceptible to poorly differentiated gastric cancers [31]; however, such mutation were not associated with other cancers [32]. On the other hand, a decline in E-cadherin protein expression is widely observed in various cancers [16].…”

Section: Discussionmentioning

confidence: 99%

A multi‐institutional study of immunohistochemical investigation for the roles of cyclin D1 and E‐cadherin in superficial squamous cell carcinoma of the esophagus*

Shiozaki¹,

Doki²,

Yamana³

et al. 2002

Journal of Surgical Oncology

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“…[13][14][15][16][17][18][19][20][21] In addition to their high risk for DGC, patients with germline CDH1 mutations carry an increased risk of lobular carcinoma of the breast and possibly colorectal and prostate cancers. 17,19,22,23 To date, CDH1 is the only gene implicated in HDGC.…”

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confidence: 99%

Hereditary diffuse gastric cancer

Cisco

Ford

Norton

2008

Cancer

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Approximately 10% of patients with gastric cancer show familial clustering, and 3% show autosomal dominance and high penetrance. Hereditary diffuse gastric cancer (HDGC) is an autosomal-dominant, inherited cancer syndrome in which affected individuals develop diffuse-type gastric cancer at a young age. Inactivating mutations in the E-cadherin gene CDH1 have been identified in 30% to 50% of patients. CDH1 mutation carriers have an approximately 70% lifetime risk of developing DGC, and affected women carry an additional 20% to 40% risk of developing lobular breast cancer. Because endoscopic surveillance is ineffective in identifying early HDGC, gene-directed prophylactic total gastrectomy currently is offered for CDH1 mutation carriers. In series of asymptomatic individuals undergoing total gastrectomy for CDH1 mutations, the removed stomachs usually contain small foci of early DGC, making surgery not prophylactic but curative.The authors of this review recommend consideration of total gastrectomy in CDH1 mutation carriers at an age 5 years younger than the youngest family member who developed gastric cancer. Individuals who choose not to undergo prophylactic gastrectomy should be followed with biannual chromoendoscopy, and women with CDH1 mutations also should undergo regular surveillance with magnetic resonance imaging studies of the breast. Because of the emergence of gene-directed gastrectomy for HDGC, today, a previously lethal disease is detected by molecular techniques, allowing curative surgery at an early stage.

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Lobular carcinoma in situ of the breast is not caused by constitutional mutations in the E-cadherin gene

Cited by 32 publications

References 18 publications

Germline E-cadherin mutations in familial lobular breast cancer

Germline E-cadherin mutations in familial lobular breast cancer

A multi‐institutional study of immunohistochemical investigation for the roles of cyclin D1 and E‐cadherin in superficial squamous cell carcinoma of the esophagus*

Hereditary diffuse gastric cancer

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