Translational advances regarding hereditary breast cancer syndromes

  title={Translational advances regarding hereditary breast cancer syndromes},
  author={Michele M. Gage and Daniel J Wattendorf and L Henry},
  journal={Journal of Surgical Oncology},
Approximately 5–10% of breast cancers may be inheritable, up to 90% of which are due to mutations in BRCA1 and BRCA2. A substantial minority are caused by non‐BRCA mutations, such as TP53, PTEN, STK11, CHEK2, ATM, BRIP1, and PALB2 mutations. This review highlights translational research advances with regard to the development of probabilistic models for hereditary breast cancer syndromes, the identification of specific genetic mutations responsible for these syndromes, as well as their testing… 
Beyond BRCA: new hereditary breast cancer susceptibility genes.
Familial Breast Cancer and Genetic Predisposition in Breast Cancer
BRCA1, BRCA2, and TP53 genes are associated with a high risk of developing breast cancer in carriers and hence are referred to as high-penetrance genes, while single nucleotide polymorphisms (SNPs) are considered low penetrance.
Breast cancer risk associated with CHEK2 mutations.
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Increasingly, oncology nurses will encounter patients and families affected with mutations on this gene and need to understand the implications it has for screening and treatment.
A review of inherited cancer susceptibility syndromes.
Signs and symptoms of the more common cancer syndromes, including hereditary breast and ovarian cancer, Li-Fraumeni, Lynch, familial adenomatous polyposis, retinoblastoma, multiple endocrine neoplasia, and von Hippel-Lindau are described.
Multiple-gene panel analysis in a case series of 255 women with hereditary breast and ovarian cancer
These patients had a much higher percentage of bilateral breast cancer (BBC) and a lower rate of OC than BRCA-mutated patients and patients with no pathogenic mutations: as a consequence, the surveillance protocol should be customized to the patient genetic characteristics.
Hereditary Breast Cancer Genetics and Risk Prediction Techniques
Increased familial breast cancer risk is also observed in families testing negative for high-risk germline mutations, suggesting that polygenic interactions of multiple lower-penetrance susceptibility alleles, in addition to traditional breast cancerrisk factors, are important causes of familial Breast cancer.
Biomarkers for Early Detection of Familial Breast Cancer
Known genetic biomarkers are summarized and testing for well-characterized mutations in blood based on a clinical suspicion of familial cancer is a well-known approach for genetic testing in cancer susceptibility.
Considerations in Testing for Inherited Breast Cancer Predisposition in the Era of Personalized Medicine.
First evidence of a large CHEK2 duplication involved in cancer predisposition in an Italian family with hereditary breast cancer
An Italian family with a high number of cases of breast cancer and other types of tumour subjected to the MLPA test to verify the presence of BRC a1, BRCA2 and CHEK2 deletions and duplications was described, and a new 23-kb duplication in the CHEk2 gene extending from intron 5 to 13 was identified that was associated with breast cancer in the family.
Genetic Predisposition to Breast and Ovarian Cancers: How Many and Which Genes to Test?
The past and more recent findings in the field of cancer predisposition genes are summarized, with insights into the role of the encoded proteins and the associated genetic disorders.


Hereditary breast cancer: new genetic developments, new therapeutic avenues
Gaining deeper insights in breast cancer susceptibility will improve the ability to identify those families at increased risk and permit the development of new and more specific therapeutic approaches, and discuss how they can be targeted by various drugs.
ATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles
The results demonstrate that ATM mutations that cause ataxia-telangiectasia in biallelic carriers are breast cancer susceptibility alleles in monoallelic carriers, with an estimated relative risk of breast cancer.
BRCA1 and BRCA2: 1994 and beyond
The discovery of the first gene associated with hereditary breast cancer, BRCA1, was anticipated to greatly increase our understanding of both hereditary and sporadic forms of breast cancer, and to
Germline TP53 mutations and Li‐Fraumeni syndrome
The spectrum of mutations and the methods for mutation detection, the tumors associated with inheritance of a germline mutation, and some of the ethical and clinical problems in patients with a germ line TP53 mutation are discussed.
The emerging landscape of breast cancer susceptibility
The genetic basis of inherited predisposition to breast cancer has been assiduously investigated for the past two decades and three reasonably well-defined classes of breast cancer susceptibility alleles with different levels of risk and prevalence in the population have become apparent.
Tumors associated with p53 germline mutations: a synopsis of 91 families.
The location of mutations within the p53 gene was found to be similar to that of somatic mutations in sporadic tumors, and there is no evidence of an organ or target cell specificity of p53 germline mutations; the occasional familial clustering of certain tumor types is more likely to reflect the genetic background of the respective kindred or the additional influence of environmental and nongenetic host factors.
Low-penetrance susceptibility to breast cancer due to CHEK2*1100delC in noncarriers of BRCA1 or BRCA2 mutations
The biological mechanisms underlying the elevated risk of breast cancer in CHEK2 mutation carriers are already subverted in carriers of BRCA1 or BRCa2 mutations, which is consistent with participation of the encoded proteins in the same pathway.
Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome
Mutational analysis of PTEN in CD kindreds has identified germline mutations that are predicted to disrupt the protein tyrosine/dual-specificity phosphatase domain of this gene, and implies that PTEN may play a role in organizing the relationship of different cell types within an organ during development.
P53 germline mutations in childhood cancers and cancer risk for carrier individuals
The family history of cancer in children treated for a solid malignant tumour in the Paediatric Oncology Department at Institute Gustave-Roussy, has been investigated and 17 germline p53 mutations were identified, of which 13 were inherited and four were de novo.