Genetic Alterations in Familial Breast Cancer: Mapping and Cloning Genes Other Than BRCAl

1997 ◽  
Author(s):  
Mary-Claire King
Keyword(s):  
Breast Cancer ◽  
Familial Breast Cancer ◽  
Genetic Alterations

scholarly journals Review of: The rare ERBB2 variant Ile654Val is associated with an increased familial breast cancer risk

2005 ◽  
Vol 8 (12) ◽  
pp. 1-3
Author(s):  
I. G. Campbell
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Familial Breast Cancer ◽  
Transmembrane Domain ◽  
Genetic Alterations ◽  
Nucleotide Polymorphisms ◽  
Breast Cancers ◽  
Increased Risk ◽  
Familial Breast Cancer Risk

Citation of original article:B. Frank, K. Hemminki, M. Wirtenberger, J. L. Bermejo, P. Bugert, R. Klaes, R. K. Schmutzler, B. Wappenschmidt, C. R. Bartram, B. Burwinkel. The rare ERBB2 variant lle654Val is associated with an increased familial breast cancer risk. Carcinogenesis 2005; 26: 643–7.Abstract of the original articleOverexpression of the proto-oncogene ERBB2 (HER2/NEU) has been observed in 20–30% of breast cancers involving poor prognosis. Genetic alterations within ERBB2 have been shown to induce carcinogenesis and metastasis. We investigated eight annotated single nucleotide polymorphisms for occurrence in familial breast cancer samples. The confirmed variants Ile654Val, Ile655Val and Ala1170Pro were analysed in subsequent epidemiological studies on familial breast cancer risk. While Ala1170Pro resides within a C-terminally located regulatory domain, the two adjacent polymorphisms Ile654Val and Ile655Val are part of the transmembrane domain. A case–control study analysing a cohort of 348 German familial breast cancer cases and 960 corresponding controls showed no significant association of either Ile655Val (OR = 1.05, 95% CI = 0.82–1.34, P = 0.728) or Ala1170Pro (OR = 0.94, 95% CI = 0.74–1.20, P = 0.632) with familial breast cancer risk. Differences in haplotype frequencies between cases and controls could also not be detected. The ERBB2 variant Ile654Val, however, revealed an increased risk for carriers of the heterozygous Val654 allele (OR = 2.56, 95% CI = 1.08–6.08, P = 0.028). The rare Val654 variant is linked with the more frequent Val655, resulting in two consecutive valine instead of two isoleucine residues within the transmembrane domain. Computational analyses suggest that the Val654–Val655 allele provokes receptor dimerisation and activation, thus stimulating kinase activity and cell transformation. We hypothesise that ERBB2 Val654 represents an oncogenic variant which might, in addition, influence clinical outcome and predict a worse prognosis.

scholarly journals Genetic Susceptibility to Breast cancer in East Azerbaijan, Iran

2018 ◽  
Vol 15 (2) ◽  
pp. 469-473
Author(s):  
Mahdiyeh Pashaei ◽  
Jamal Eivazi Ziaei ◽  
Alireza Nikanfar ◽  
Babak Emamalizadeh ◽  
Seyyed Mojtaba Mohaddes Ardebili
Keyword(s):  
Breast Cancer ◽  
Familial Breast Cancer ◽  
Cancer Susceptibility ◽  
Positive Family History ◽  
Critical Factor ◽  
Breast Cancer Susceptibility ◽  
Genetic Alterations ◽  
Brca1 And Brca2 ◽  
Cancer Susceptibility Genes ◽  
East Azerbaijan

Breast cancer is the most common cause of death among women in the world and in Iran. A number of risk factors for breast cancer development have been identified, among which the most important is positive family history. Alterations in different genes, including BRCA1, BRCA2, p53, CHEK2, PTEN, and ATM, also induce a predisposition for breast cancer. Among these changes, BRCA1 and BRCA2 alterations are the strongest drivers of breast cancer predisposition. This study was aimed at contributing to the development of appropriate methods for detecting genetic alterations, such as single or multiple exon deletions and amplifications, in the aforementioned genes. We used multiplex ligation-dependent probe amplification (MLPA) to determine genetic alterations in 150 female patients who hail from East Azerbaijan, Iran and suffer from familial breast cancer. Specifically, we investigated copy number changes in BRCA1, ATM, p53, CHEK2, and PTEN. MLPA results showed no remarkable mutations in the study population. Size coverage is a critical factor for MLPA to accurately detect potential mutations in familial breast cancer susceptibility genes.

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.

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