Pathology and gene expression of hereditary breast tumors associated with BRCA1, BRCA2 and CHEK2 gene mutations

  title={Pathology and gene expression of hereditary breast tumors associated with BRCA1, BRCA2 and CHEK2 gene mutations},
  author={Emiliano Honrado and Ana Osorio and Jos{\'e} Palacios and Javier Ben{\'i}tez},
Tumors arising in BRCA1 and BRCA2 mutation carriers appear to have specific pathological and gene expression profiles, which show a high level of concordance. BRCA1 tumors are high-grade, negative for hormone receptors, have a high proliferation rate, and are positive for some cell cycle promoter genes. BRCA2 tumors present a phenotype opposite to BRCA1 tumors but very similar to sporadic tumors, except that BRCA2 overexpress some DNA repair markers such as CHEK2, show high cytoplasmic… 
Transcriptional signature of lymphoblastoid cell lines of BRCA1, BRCA2 and non-BRCA1/2 high risk breast cancer families
This represents the first study identifying transcripts differentially expressed in lymphoblastoid cell lines from major classes of mutation-related breast cancer subgroups, namely BRCA1, BRCa2 and BRCAX, which could represent potential therapeutic targets for breast cancer treatment.
Pathology of hereditary breast cancer
A better understanding of the morphological, immunohistochemical and molecular characteristics of different types of hereditary breast cancers is led, which offer clues for diagnosis and new therapeutic approaches.
The contribution of breast cancer pathology to statistical models to predict mutation risk in BRCA carriers
The evidence to justify the use of pathology in refining risk assessment models is assessed and it is shown that although breast tumours are heterogeneous, there are histological characteristics that are seen more frequently in carriers of BRCA1 germ line mutations compared to BRC a2 and sporadic breast cancers.
Reviewing the characteristics of BRCA and PALB2-related cancers in the precision medicine era
Abstract Germline mutations in BRCA1 and BRCA2 (BRCA) genes confer high risk of developing cancer, especially breast and ovarian tumors. Since the cloning of these tumor suppressor genes over two
Characteristics of triple-negative breast cancer in patients with a BRCA1 mutation: results from a population-based study of young women.
Among BRCA1 mutation carriers, as among noncarriers, there are unique characteristics associated with the triple-negative subtype, and Ashkenazi Jewish women were about five times more likely to have TNBC than non-AshkenaziJewish women.
The Pathology of Hereditary Breast Cancer
The role of BRCA1 and BRCa2 in DNA repair is being exploited to develop novel therapies, for example, using the poly-ADP-ribose polymerase inhibitors.
BRCA1/BRCA2 mutation status and clinical-pathologic features of 108 male breast cancer cases from Tuscany: a population-based study in central Italy
Background Male breast cancer (MBC) is a rare and scarcely investigated disease. The strongest genetic risk factor for MBC is represented by inherited BRCA2 mutations, whereas the association between
Hereditary breast cancer: from molecular pathology to tailored therapies
The hallmark histological features of these carcinomas compared with non-hereditary breast cancers are described and it is shown how an accurate histopathological diagnosis may help improve the identification of patients to be screened for mutations.
MicroRNA expression profiles in hereditary breast cancer
The data suggest a role for BRCA1 in modulating a number of miRNAs and indirectly hundreds of genes, in turn promoting the repression of NF-?B and MAPK signaling pathways in breast cancer, implying a common pathway of tumor progression irrespective of the initiating events.
Effect of CHEK2 missense variant I157T on the risk of breast cancer in carriers of other CHEK2 or BRCA1 mutations
The risk of breast cancer in carriers of a deleterious CHEK2 mutation is increased if the second allele is the I157T missense variant, however, the presence of a CHEk2 mutation in women with a BRCA1 mutation may not increase their risk beyond that of the BRCa1 mutation alone.


Immunohistochemical expression of DNA repair proteins in familial breast cancer differentiate BRCA2-associated tumors.
  • E. Honrado, A. Osorio, J. Benítez
  • Medicine, Biology
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2005
The results suggest that BRCA2 tumors demonstrate more cytoplasmic and less nuclear RAD51 staining, and increased CHEK2 staining that may distinguish BRCa2 from familial non-BRCA1/2 tumors.
Gene-expression profiles in hereditary breast cancer.
Significantly different groups of genes are expressed by breast cancers with BRCA1 mutations and breast cancersWith BRCa2 mutations, the results suggest that a heritable mutation influences the gene-expression profile of the cancer.
Phenotypic characterization of BRCA1 and BRCA2 tumors based in a tissue microarray study with 37 immunohistochemical markers
The study in hereditary breast cancer tumors analyzing 37 immunohistochemical markers defines the molecular differences between BRCA1 and BRCa2 tumors with respect to hormonal receptors, cell cycle, apoptosis and basal cell markers.
The pathology of familial breast cancer: predictive value of immunohistochemical markers estrogen receptor, progesterone receptor, HER-2, and p53 in patients with mutations in BRCA1 and BRCA2.
The combined morphologic and immunohistochemical data can be used to predict the risk of a young patient harboring a germline mutation in BRCA1, and the BRC a2 phenotype is currently not well defined.
Phenotypic effects of heterozygosity for a BRCA2 mutation.
It is demonstrated that, in a specific vertebrate cell type, the chicken B cell line DT40, heterozygosity for a BRCA2 mutation has a distinct phenotype, characterized by a reduced growth rate, increased cell death, heightened sensitivity to specific DNA damaging agents and reduced RAD51 focus formation after irradiation.
Low expression of bcl-2 in Brca1-associated breast cancers
A low expression of bcl-2 characterises most Brca1-associated breast carcinomas, a biological trait which seems not to be shared by Brca2-associated tumours nor to be related to oestrogen receptor and/or p53 status.
Inherited BRCA2 mutation associated with high grade breast cancer
According to the results of this study, hereditary breast cancers associated with the 999del5 BRCA2 mutation are high grade tumors with a rapid proliferation rate.
The pathology of familial breast cancer: Immunohistochemistry and molecular analysis
BRCA1-associated tumours appear to show an increased frequency of TP53 mutations, frequent p53 protein stabilization and absence of imunoreactivity for steroid hormone receptors, according to morphological studies.
Molecular classification of familial non-BRCA1/BRCA2 breast cancer
It is shown that gene expression profiling can discover novel classes among BRCAx tumors, and differentiate them from BRCA1 and BRC a2 tumors, illustrating that, when gene expression-based classifications are used, BRC Ax families can be grouped into homogeneous subsets, thereby potentially increasing the power of conventional genetic analysis.