scholarly journals Increased gene expression variability in BRCA1-associated and basal-like breast tumours

2021 ◽  
Author(s):  
George A. R. Wiggins ◽  
Michael A. Black ◽  
Anita Dunbier ◽  
Arthur E. Morley-Bunker ◽  
John F. Pearson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Susceptibility ◽  
Expression Patterns ◽  
In Situ Hybridisation ◽  
Breast Cancers ◽  
Breast Tumours ◽  
Expression Variability ◽  
Cancer Susceptibility Genes

Abstract Purpose Inherited variants in the cancer susceptibility genes, BRCA1 and BRCA2 account for up to 5% of breast cancers. Multiple gene expression studies have analysed gene expression patterns that maybe associated with BRCA12 pathogenic variant status; however, results from these studies lack consensus. These studies have focused on the differences in population means to identified genes associated with BRCA1/2-carriers with little consideration for gene expression variability, which is also under genetic control and is a feature of cellular function. Methods We measured differential gene expression variability in three of the largest familial breast cancer datasets and a 2116 breast cancer meta-cohort. Additionally, we used RNA in situ hybridisation to confirm expression variability of EN1 in an independent cohort of more than 500 breast tumours. Results BRCA1-associated breast tumours exhibited a 22.8% (95% CI 22.3–23.2) increase in transcriptome-wide gene expression variability compared to BRCAx tumours. Additionally, 40 genes were associated with BRCA1-related breast cancers that had ChIP-seq data suggestive of enriched EZH2 binding. Of these, two genes (EN1 and IGF2BP3) were significantly variable in both BRCA1-associated and basal-like breast tumours. RNA in situ analysis of EN1 supported a significant (p = 6.3 × 10−04) increase in expression variability in BRCA1-associated breast tumours. Conclusion Our novel results describe a state of increased gene expression variability in BRCA1-related and basal-like breast tumours. Furthermore, genes with increased variability may be driven by changes in DNA occupancy of epigenetic effectors. The variation in gene expression is replicable and led to the identification of novel associations between genes and disease phenotypes.

FOXA1 in breast cancer

2009 ◽  
Vol 11 ◽  
Author(s):  
Harikrishna Nakshatri ◽  
Sunil Badve
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Transcription Factor ◽  
Expression Patterns ◽  
Gene Expression Pattern ◽  
Gene Expression Signature ◽  
Specific Gene ◽  
Breast Cancers ◽  
Transcription Factor Network ◽  
Histopathological Classification

Breast cancer is a heterogeneous disease and classification is important for clinical management. At least five subtypes can be identified based on unique gene expression patterns; this subtype classification is distinct from the histopathological classification. The transcription factor network(s) required for the specific gene expression signature in each of these subtypes is currently being elucidated. The transcription factor network composed of the oestrogen (estrogen) receptor α (ERα), FOXA1 and GATA3 may control the gene expression pattern in luminal subtype A breast cancers. Breast cancers that are dependent on this network correspond to well-differentiated and hormone-therapy-responsive tumours with good prognosis. In this review, we discuss the interplay between these transcription factors with a particular emphasis on FOXA1 structure and function, and its ability to control ERα function. Additionally, we discuss modulators of FOXA1 function, ERα–FOXA1–GATA3 downstream targets, and potential therapeutic agents that may increase differentiation through FOXA1.

scholarly journals Gene Mutations in Hereditary Breast Cancer- A Review

2020 ◽  
Vol 2 (3) ◽  
Author(s):  
Pathima Fairoosa ◽  
Chamindri Witharana
Keyword(s):  
Breast Cancer ◽  
Hereditary Breast Cancer ◽  
Cancer Susceptibility ◽  
Gene Mutations ◽  
Tumour Suppressor Genes ◽  
Breast Cancers ◽  
Germline Gene ◽  
Brca1 And Brca2 ◽  
Repair Gene ◽  
Cancer Susceptibility Genes

The most prevalent form of cancer in females is breast cancer. Roughly 5%-10% of breast cancers are hereditary, and they are associated with Germline gene mutations, inherited from parents. Germline gene mutations increase the risk of developing cancer earlier in life compared to noninherited cases (sporadic cancer). BRCA1 and BRCA2 are well-studied tumour suppressor genes associated with hereditary breast cancer. Even though mutations in BRCA1 and BRCA2 are assumed to responsible the majority of hereditary breast cancers cases, many other breast cancer susceptibility genes have been identified in the last few decades. Identification of many germline mutations was possible due to advance sequencing technologies. Most of these genes are belongs to tumour suppressors and DNA damage repair gene families (DNA double-strand break repair and DNA mismatch repair). These genes play a vital role in genomic stability and cell cycle control suggesting that any alteration in these genes trigger uncontrolled growth and tumour formation. These genes are categorized according to the penetrance level, the proportion of carriers express the associated trait of the mutated gene. Mutations in high penetrance genes such as BRCA1, BRCA2, TP53, PTEN, and SKT11 greatly increase the risk of developing breast cancer. Moderate penetrance gene such as PALB2, ATM, CHEK2, BARD1, BRIP1 and low penetrance gene such as PARP4, CASP8, TOX3 confer moderate to low increase risk of developing breast cancer. Aim of this review is to summarize genes associated with hereditary breast cancer according to their penetrance level (high, moderate and low penetrance).

scholarly journals Exonic sequencing and MLH3 gene expression analysis of breast cancer patients

2021 ◽  
Vol 67 (3) ◽  
pp. 35-43
Author(s):  
Rozhgar A. Khailany ◽  
Mehmet Ozaslan
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Exome Sequencing ◽  
Cancer Patients ◽  
Cancer Susceptibility ◽  
Susceptibility Gene ◽  
Breast Cancer Susceptibility ◽  
Breast Cancer Patients ◽  
Cancer Susceptibility Genes ◽  
Mlh3 Gene

Breast cancer is the most common cancer in women worldwide. Detection of breast cancer susceptibility genes is an important issue. Also, MLH3 is a DNA mismatch repair gene and mutation in this gene is harmful in different cancers. This study aimed to use exome sequencing to uncover previously undetected breast cancer-predisposing variants. Also, we investigated the MLH3 gene expression of breast cancer patients which can be a breast cancer susceptibility gene. A total of 80 samples including 40 paired normal and cancer tissue samples were collected at Zheen International Hospital, Erbil, Iraq. Exome sequencing was used to identify mutations. Different in silico tools were used to predict the effect of mutation on the structural features or protein function. Real-time PCR was used for assessing the expression of MLH3 in breast cancer patients. We identified 26 variants in breast cancer patients, 22 inherited variants were found in MLH3, CHECK2, BRCA1, BRCA2, BLM, TP53, MSH6, NBN and PTEN genes and 4 somatic variants were found in PALB2, RAD50 and RBM10 genes. It was found that the expression of the MLH3 gene in tumor samples was significantly down-regulated compared with normal tissues. Statistically, high significance was found. The decreased expression of MLH3 was significant in all ranges of ages and all breast cancer types. Also, the expression of MLH3 decreased significantly in patients with breast cancer grades of II and III. In conclusion, MLH3 can be used as a susceptibility gene especially in grades II and III of breast cancer.

scholarly journals Haplotypes associated to gene expression in breast cancer: can they lead us to the susceptibility markers?

2018 ◽  
Author(s):  
Hege Edvardsen ◽  
Bettina Kulle ◽  
Anya Tsalenko ◽  
Grethe Irene Grenaker Alnӕs ◽  
Fredrik Ekeberg Johansen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Patients ◽  
Haplotype Analysis ◽  
Cancer Susceptibility ◽  
Expression Patterns ◽  
Breast Cancer Patients ◽  
Haplotype Distribution ◽  
Significant Difference ◽  
History Of

AbstractWe have undertaken a systematic haplotype analysis of the positional type of biclusters analysing samples collected from 164 breast cancer patients and 86 women with no known history of breast cancer. We present here the haplotypes and LD patterns in more than 80 genes distributed across all chromosomes and how they differ between cases and controls. We aim by this to 1) identify genes with different haplotype distribution or LD patterns between breast cancer patients and controls and 2) to evaluate the intratumoral mRNA expression patterns in breast cancer associated particularly to the cancer susceptibility haplotypes. A significant difference in haplotype distribution between cases and controls was observed for a total of 35 genes including ABCC1, AKT2, NFKB1, TGFBR2 and XRCC4. In addition we see a negative correlation between LD patterns in cases and controls for neighboring markers in 8 genes such as CDKN1A, EPHX1 and XRCC1.

scholarly journals Orbital Metastases from Breast Cancer with BRCA2 Mutation: A Case Report and Literature Review

2018 ◽  
Vol 11 (2) ◽  
pp. 360-364
Author(s):  
Emily Barber ◽  
Yung Lyou ◽  
Rita Mehta ◽  
Erin Lin ◽  
Karen Lane ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Susceptibility ◽  
Major Gene ◽  
Brca2 Mutation ◽  
The United States ◽  
Breast Cancers ◽  
Cns Metastases ◽  
Rare Presentation ◽  
Orbital Metastases ◽  
Cancer Susceptibility Genes

Breast cancer is the second leading cause of cancer-related deaths in women in the United States. Of these women, 5–10% have an inherited form of breast cancer with a mutation in a major gene, such as the breast cancer susceptibility genes 1 or 2 (BRCA1 or BRCA2). Triple negative (the most common subtype of BRCA1-associated breast cancers) and Her2-positive breast cancer patients have more frequently been observed to develop central nervous system (CNS) metastases compared to other molecular subtypes of breast cancers. However, it remains an open question if BRCA2-associated breast cancers also have a higher propensity to develop CNS metastases. Here we report a rare case of recurrent BRCA2-associated breast cancer which manifested as orbital metastases. At the time of this publication, this is one of the first cases of BRCA2-associated breast cancer to present with orbital metastases. In this article, we discuss the diagnostic challenges and review the literature regarding this rare presentation.

scholarly journals Gene-expression patterns in peripheral blood classify familial breast cancer susceptibility

2015 ◽  
Vol 8 (1) ◽  
Author(s):  
Stephen R. Piccolo ◽  
Irene L. Andrulis ◽  
Adam L. Cohen ◽  
Thomas Conner ◽  
Philip J. Moos ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Peripheral Blood ◽  
Familial Breast Cancer ◽  
Cancer Susceptibility ◽  
Expression Patterns ◽  
Breast Cancer Susceptibility ◽  
Gene Expression Patterns

scholarly journals A systematic review: breast cancer susceptibility genes

2020 ◽  
Vol 218 ◽  
pp. 03039
Author(s):  
ZhiLan Xie
Keyword(s):  
Breast Cancer ◽  
Cancer Susceptibility ◽  
Normal Population ◽  
Breast Cancer Susceptibility ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Cancer Susceptibility Genes ◽  
Cell Life ◽  
Dominant Female ◽  
Cell To Cell Adhesion

Breast cancer is the dominant female cancer and the top cause of cancer deaths in women among the world. The susceptible genes are critical risk factors for both hereditary and sporadic breast cancers. The incidence of carcinoma for carriers with mutated relative genes might increase in comparison with that of the normal population. These genes might be applied in breast cancer populated screening and clinical treatment, in order to improve survival of the breast cancer patients. This study concluded some genes involved in various key elementary processes in cell life, including DNA repair, cell cycle regulation, cell-to-cell adhesion and metabolism, in previous research.

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