scholarly journals Germline Mutations in CDH1 and the Hereditary Diffuse Gastric and Lobular Breast Cancer Syndrome

2012 ◽  
Vol 23 ◽  
pp. ix175
Author(s):  
P.R. Benusiglio ◽  
D. Malka ◽  
A. De Pauw ◽  
B. Buecher ◽  
E. Rouleau ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Germline Mutations ◽  
Lobular Breast Cancer ◽  
Cancer Syndrome

scholarly journals Clinical spectrum and pleiotropic nature of CDH1 germline mutations

2019 ◽  
Vol 56 (4) ◽  
pp. 199-208 ◽  
Author(s):  
Joana Figueiredo ◽  
Soraia Melo ◽  
Patrícia Carneiro ◽  
Ana Margarida Moreira ◽  
Maria Sofia Fernandes ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gastric Cancer ◽  
Genetic Alterations ◽  
Tumour Suppressor Gene ◽  
Diffuse Gastric Cancer ◽  
Loss Of Function ◽  
Lobular Breast Cancer ◽  
Cancer Syndrome ◽  
Risk Of Cancer ◽  
E Cadherin

CDH1 encodes E-cadherin, a key protein in adherens junctions. Given that E-cadherin is involved in major cellular processes such as embryogenesis and maintenance of tissue architecture, it is no surprise that deleterious effects arise from its loss of function. E-cadherin is recognised as a tumour suppressor gene, and it is well established that CDH1 genetic alterations cause diffuse gastric cancer and lobular breast cancer—the foremost manifestations of the hereditary diffuse gastric cancer syndrome. However, in the last decade, evidence has emerged demonstrating that CDH1 mutations can be associated with lobular breast cancer and/or several congenital abnormalities, without any personal or family history of diffuse gastric cancer. To date, no genotype–phenotype correlations have been observed. Remarkably, there are reports of mutations affecting the same nucleotide but inducing distinct clinical outcomes. In this review, we bring together a comprehensive analysis of CDH1-associated disorders and germline alterations found in each trait, providing important insights into the biological mechanisms underlying E-cadherin’s pleiotropic effects. Ultimately, this knowledge will impact genetic counselling and will be relevant to the assessment of risk of cancer development or congenital malformations in CDH1 mutation carriers.

CDH1 germline mutations and hereditary lobular breast cancer

2016 ◽  
Vol 15 (2) ◽  
pp. 215-219 ◽  
Author(s):  
Giovanni Corso ◽  
Mattia Intra ◽  
Chiara Trentin ◽  
Paolo Veronesi ◽  
Viviana Galimberti
Keyword(s):  
Breast Cancer ◽  
Germline Mutations ◽  
Lobular Breast Cancer

Clinical criteria revision for hereditary lobular breast cancer associated with E-cadherin germline mutations

2018 ◽  
Vol 15 (3) ◽  
pp. 153-155 ◽  
Author(s):  
Giovanni Corso ◽  
Alessandra De Scalzi ◽  
Irene Feroce ◽  
Paolo Veronesi ◽  
Bernardo Bonanni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Germline Mutations ◽  
Lobular Breast Cancer ◽  
Clinical Criteria ◽  
E Cadherin

CDH1 germline mutations in families with hereditary lobular breast cancer

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Antonia Girardi ◽  
Francesca Magnoni ◽  
Elisa Vicini ◽  
Andriana Kouloura ◽  
Carlo La Vecchia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Germline Mutations ◽  
Lobular Breast Cancer

scholarly journals Detection of Germline Mutations in Breast Cancer Patients with Clinical Features of Hereditary Cancer Syndrome Using a Multi-Gene Panel Test

2020 ◽  
Vol 52 (3) ◽  
pp. 697-713
Author(s):  
Hee-Chul Shin ◽  
Han-Byoel Lee ◽  
Tae-Kyung Yoo ◽  
Eun-Shin Lee ◽  
Ryong Nam Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Clinical Features ◽  
Germline Mutations ◽  
Gene Panel ◽  
Hereditary Cancer Syndrome ◽  
Deleterious Mutations ◽  
Breast Cancer Patients ◽  
Cancer Syndrome ◽  
Multiple Gene

PurposeHereditary cancer syndrome means that inherited genetic mutations can increase a person's risk of developing cancer. We assessed the frequency of germline mutations using an nextgeneration sequencing (NGS)–based multiple-gene panel containing 64 cancer-predisposing genes in Korean breast cancer patients with clinical features of hereditary breast and ovarian cancer syndrome (HBOC).Materials and MethodsA total of 64 genes associated with hereditary cancer syndrome were selected for development of an NGS-based multi-gene panel. Targeted sequencing using the multi-gene panel was performed to identify germline mutations in 496 breast cancer patients with clinical features of HBOC who underwent breast cancer surgery between January 2002 and December 2017.ResultsOf 496 patients, 95 patients (19.2%) were found to have 48 deleterious germline mutations in 16 cancer susceptibility genes. The deleterious mutations were found in 39 of 250 patients (15.6%) who had breast cancer and another primary cancer, 38 of 169 patients (22.5%) who had a family history of breast cancer (≥ 2 relatives), 16 of 57 patients (28.1%) who had bilateral breast cancer, and 29 of 84 patients (34.5%) who were diagnosed with breast cancer at younger than 40 years of age. Of the 95 patients with deleterious mutations, 60 patients (63.2%) had <i>BRCA1/2</i> mutations and 38 patients (40.0%) had non-<i>BRCA1/2</i> mutations. We detected two novel deleterious mutations in <i>BRCA2</i> and <i>MLH1</i>.ConclusionNGS-based multiple-gene panel testing improved the detection rates of deleterious mutations and provided a cost-effective cancer risk assessment.

THE ASSOCIATION OF LOBULAR BREAST CANCER WITH GERMLINE MUTATIONS OF CDH1

2008 ◽  
Vol 31 (4) ◽  
pp. 22
Author(s):  
K Schrader ◽  
S Masciari ◽  
N Boyd ◽  
J Senz ◽  
P Kaurah ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Early Onset ◽  
Dna Analysis ◽  
Control Sample ◽  
Germline Mutations ◽  
Diffuse Gastric Cancer ◽  
Missense Mutations ◽  
Lobular Breast Cancer ◽  
History Of

Background: CDH1 encodes the cell-cell adhesion molecule, E-cadherin, for which loss of expression facilitates the infiltrative and metastatic potential of cancers. Germline mutations in CDH1 are associated with hereditary diffuse gastric cancer (HDGC), and in this setting female carriers have been estimated to have a 39-50% risk of lobular breast cancer (LBC) by age 80 years. Aim: To determine the frequency of CDH1 germline mutations inindividuals with early-onset LBC or those with LBC and a family history of multiple breast cancers but no gastric cancers. Methods: Germline DNA analysis of CDH1 in women with LBC, for whom germline BRCA1 and BRCA2 mutations have been excluded, who have been (1) diagnosed before the age of 45 years or (2) diagnosed at any age and have a family history of breast cancer. Results: Analysis of 194 LBC cases has thus far revealed two novel missense mutations predicted to affect protein function. Functional assays to assess their pathogenicity along with germline analyses of the remaining 200 cases are currently underway. Several unreported silent changes have also been identified and will be measured in a case- control sample to assess whether they are associated with LBC risk. Conclusion: Germline CDH1 mutations may cause a small proportion of familial and early onset LBC.

CDH1germline mutations and the hereditary diffuse gastric and lobular breast cancer syndrome: a multicentre study

2013 ◽  
Vol 50 (7) ◽  
pp. 486-489 ◽  
Author(s):  
Patrick R Benusiglio ◽  
David Malka ◽  
Etienne Rouleau ◽  
Antoine De Pauw ◽  
Bruno Buecher ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Multicentre Study ◽  
Lobular Breast Cancer ◽  
Cancer Syndrome

Clinical application of polymorphic variants of the genes ESR1 and CYP2D6*4 in patients with breast and endometrial cancer

2017 ◽  
pp. 132-138
Author(s):  
O.V. Paliychuk ◽  
◽  
L.Z. Polishchuk ◽  
Z.I. Rossokha ◽  
◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endometrial Cancer ◽  
Hormone Therapy ◽  
Molecular Genetic ◽  
Cancer Syndrome ◽  
Genetic Characteristics ◽  
Multiple Tumors ◽  
Receptor Status ◽  
Genetic Examination ◽  
The Impact

The objective: determining gene polymorphism features ERS1, CYP2D6 in patients with breast cancer (RHZ) and endometrial cancer (EC) and the impact assessment studied genetic characteristics compared to receptor status (immunohistochemical determination of expression levels of ER, PR) tumors and the results of the treatment. Patients and methods. article presents the results of complex clinical, morphological, clinical-genealogical, and molecular-genetic examination of 28 females: 19 patients with breast cancer (BC), 9 patients with endometrial cancer (EC), including 5 patients with primary-multiple tumors (PMT) with and without tumor pathology aggregation in families. Results. The It was determined that in patients’ families malignant tumors of breast, uterine body and/or ovaries prevail that corresponds to Lynch type II syndrome (family cancer syndrome). Molecular-genetic examination of genomic DNA of peripheral blood and histological sections for the presence of SNPs of ESR and CYP2D6*4 genes comparing with the results of immunohistochemical study of tumors for receptors ER and PR status have not found associations between these characteristics; although among EC patients the occurrence of genotypes 397ТТ and 351АА was significantly higher comparing with BC patients (55.55% and 10.5% for genotype 397ТТ,and 15.8% for genotype 351АА, respectively). At the same time the patients with BC and primary-multiple tumors (PMT) of female reproductive system organs (FRSO) that carried mutations in BRCA1 in all the cases demonstrated positive ER and PR receptor status and adverse combinations of polymorphous variants of the genes ESR1 (397СС, 397ТС) and CYP2D6*4 (1846G, 1846GA), suggesting combined effect of these factors on the development of malignant neoplasias of FRSO in families with positive family cancer history. In BC patients, receiving standard hormone therapy with tamoxifen, those, who had genotype 1846GG of the gene CYP2D6*4, in 3 patients (15.8%) of 19 (100%) patients disease recurrence was diagnosed. Conclusion. The obtained results allow clinical use of the assessment of polymorphism frequency of the genes ESR1 and CYP2D6*4 for selection of individual hormone therapy regimens schemes for BC patients, to increase efficacy of dispensary observation after finishing of special therapy for such patients, and also personalization of complex and combined treatment regimens. Key words: breast cancer, endometrial cancer, family cancer syndrome, single nucleotide polymorphisms (SNPs) of the genes ESR1, CYP2D6*4.

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