scholarly journals Detection of PIK3CA Gene Mutations with HRM Analysis and Association with IGFBP-5 Expression Levels in Breast Cancer

2014 ◽  
Vol 15 (21) ◽  
pp. 9327-9333 ◽  
Author(s):  
Ebubekir Dirican ◽  
Zehra Kaya ◽  
Gokce Gullu ◽  
Irem Peker ◽  
Tolga Ozmen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Mutations ◽  
Expression Levels ◽  
Pik3ca Gene ◽  
Hrm Analysis

Mutation distributions and clinical correlations of PIK3CA gene mutations in breast cancer

Tumor Biology ◽  
2016 ◽  
Vol 37 (6) ◽  
pp. 7033-7045 ◽  
Author(s):  
Ebubekir Dirican ◽  
Mustafa Akkiprik ◽  
Ayşe Özer
Keyword(s):  
Breast Cancer ◽  
Gene Mutations ◽  
Pik3ca Gene ◽  
Clinical Correlations

BRCA gene mutations in Slovenian male breast cancer patients

2007 ◽  
Vol 4 (03) ◽  
Author(s):  
N Besic ◽  
B Cernivc ◽  
J De Greve ◽  
K Lokar ◽  
M Krajc ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Male Breast Cancer ◽  
Gene Mutations ◽  
Male Breast ◽  
Breast Cancer Patients ◽  
Brca Gene

SOX4 Serves an Oncogenic Role in the Tumourigenesis of Human Breast Adenocarcinoma by Promoting Cell Proliferation, Migration and Inhibiting Apoptosis

2020 ◽  
Vol 15 (1) ◽  
pp. 49-58
Author(s):  
Junhe Zhang ◽  
Shujie Chai ◽  
Xinyu Ruan
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Caspase 3 ◽  
Breast Adenocarcinoma ◽  
Migration Ability ◽  
Expression Levels ◽  
Apoptosis Rate ◽  
And Migration ◽  
Mcf 7 ◽  
Proliferation And Migration

Background: Breast cancer is among the most common malignant cancers worldwide, and breast adenocarcinoma in glandular tissue cells has excessive metastasis and invasion capability. However, little is known on the molecular process by which this disease develops and progresses. Objective: In this study, we explored the effects of sex-determining region Y-box 4 (SOX4) protein on proliferation, migration, apoptosis and tumourigenesis of breast adenocarcinoma and its possible mechanisms. Methods: The SOX4 overexpression or knockdown Michigan Cancer Foundation-7 (MCF-7) cell lines were established. Among the SOX4 overexpression or MCF-7 knockdown cell lines, proliferation, migration ability and apoptosis rate were detected. The expression levels of apoptosis-related proteins (Bax and Cleaved caspase-3) were analysed using Western blot. The effect of SOX4 on tumourigenesis was analysed using the clone formation assay in vitro and tumour xenograft experiment in nude mice. Results: Compared with the overexpression of control cells, proliferation and migration ability of SOX4 overexpression cells significantly increased, the apoptosis rate significantly decreased in addition to the expression levels of Bax and Cleaved caspase-3 (P < 0.05). Compared with the knockdown of control cells, proliferation and migration ability of SOX4 knockdown cells significantly decreased, and the apoptosis rate and expression levels of Bax and Cleaved caspase-3 significantly increased (P < 0.05). Clone formation and tumour growth abilities of SOX4 overexpression cells were significantly higher than those of the control cells (P < 0.05), whereas SOX4 knockdown cells had the opposite effect. Conclusion: SOX4 plays an oncogenic role in breast adenocarcinoma tumourigenesis by promoting cell proliferation, migration and inhibiting apoptosis. It can be used as a potential molecular target for breast cancer gene therapy.

Mutation Mechanisms of Breast Cancer among the Female Population in China

2020 ◽  
Vol 15 (3) ◽  
pp. 253-259
Author(s):  
Asmaa Amer ◽  
Ahmed Nagah ◽  
Tianhai Tian ◽  
Xinan Zhang
Keyword(s):  
Breast Cancer ◽  
Gene Mutations ◽  
Driver Mutations ◽  
Human Breast ◽  
Breast Epithelium ◽  
Female Population ◽  
Multistage Model ◽  
The Usa ◽  
Intermediate Cells ◽  
Mutation Mechanisms

Background: Cancer is a genetic disease caused by the accumulation of gene mutations. It is important to derive the number of driver mutations that are needed for the development of human breast cancer, which may provide insights into the tumor diagnosis and therapy. Objective: This work is designed to investigate whether there is any difference for the mutation mechanism of breast cancer between the patients in the USA and those in China. We study the mechanisms of breast cancer development in China, and then compare these mechanisms with those in the USA. Methods: This work designed a multistage model including both gene mutation and clonal expansion of intermediate cells to fit the dataset of breast cancer in China from 2004 to 2009. Results: Our simulation results show that the maximum number of driver mutations for breast epithelium stem cells of females in China is 13 which is less than the 14 driver mutations of females in the USA. In addition, the two-hit model is the optimal one for the tumorigenesis of females in China, which is also different from the three-hit model that was predicted as the optimal model for the tumorigenesis of females in the USA. Conclusion: The differences of the mutation mechanisms between China and the USA reflect a variety of lifestyle, genetic influences, environmental exposure, and the availability of mammography screening.

scholarly journals Single Cell Genetic Profiling of Tumors of Breast Cancer Patients Aged 50 Years and Older Reveals Enormous Intratumor Heterogeneity Independent of Individual Prognosis

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3366
Author(s):  
Anna-Sophie Liegmann ◽  
Kerstin Heselmeyer-Haddad ◽  
Annette Lischka ◽  
Daniela Hirsch ◽  
Wei-Dong Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Copy Number ◽  
Genome Instability ◽  
Single Cells ◽  
Gene Mutations ◽  
Intratumor Heterogeneity ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Pik3ca Mutations

Purpose: Older breast cancer patients are underrepresented in cancer research even though the majority (81.4%) of women dying of breast cancer are 55 years and older. Here we study a common phenomenon observed in breast cancer which is a large inter- and intratumor heterogeneity; this poses a tremendous clinical challenge, for example with respect to treatment stratification. To further elucidate genomic instability and tumor heterogeneity in older patients, we analyzed the genetic aberration profiles of 39 breast cancer patients aged 50 years and older (median 67 years) with either short (median 2.4 years) or long survival (median 19 years). The analysis was based on copy number enumeration of eight breast cancer-associated genes using multiplex interphase fluorescence in situ hybridization (miFISH) of single cells, and by targeted next-generation sequencing of 563 cancer-related genes. Results: We detected enormous inter- and intratumor heterogeneity, yet maintenance of common cancer gene mutations and breast cancer specific chromosomal gains and losses. The gain of COX2 was most common (72%), followed by MYC (69%); losses were most prevalent for CDH1 (74%) and TP53 (69%). The degree of intratumor heterogeneity did not correlate with disease outcome. Comparing the miFISH results of diploid with aneuploid tumor samples significant differences were found: aneuploid tumors showed significantly higher average signal numbers, copy number alterations (CNAs) and instability indices. Mutations in PIKC3A were mostly restricted to luminal A tumors. Furthermore, a significant co-occurrence of CNAs of DBC2/MYC, HER2/DBC2 and HER2/TP53 and mutual exclusivity of CNAs of HER2 and PIK3CA mutations and CNAs of CCND1 and PIK3CA mutations were revealed. Conclusion: Our results provide a comprehensive picture of genome instability profiles with a large variety of inter- and intratumor heterogeneity in breast cancer patients aged 50 years and older. In most cases, the distribution of chromosomal aneuploidies was consistent with previous results; however, striking exceptions, such as tumors driven by exclusive loss of chromosomes, were identified.

scholarly journals The Value of EphB2 Receptor and Cognate Ephrin Ligands in Prognostic and Predictive Assessments of Human Breast Cancer

2021 ◽  
Vol 22 (15) ◽  
pp. 8098
Author(s):  
Abdul Shukkur Ebrahim ◽  
Zeyad Hailat ◽  
Sudeshna Bandyopadhyay ◽  
Daniel Neill ◽  
Mustapha Kandouz
Keyword(s):  
Breast Cancer ◽  
Distant Metastasis ◽  
Predictive Value ◽  
Intracellular Signaling ◽  
Ductal Carcinoma ◽  
Cancer Development ◽  
Eph Receptors ◽  
Free Survival ◽  
Expression Levels ◽  
Ephrin Ligands

Cell–cell communication proteins Eph and ephrin constitute the largest family of receptor tyrosine kinases (RTKs). They are distinguished by the fact that both receptors and ligands are membrane-bound, and both can drive intracellular signaling in their respective cells. Ever since these RTKs have been found to be involved in cancer development, strategies to target them therapeutically have been actively pursued. However, before this goal can be rationally achieved, the contributions of either Eph receptors or their ephrin ligands to cancer development and progression should be scrutinized in depth. To assess the clinical pertinence of this concern, we performed a systematic review and meta-analysis of the prognostic/predictive value of EphB2 and its multiple cognate ephrin ligands in breast cancer. We found that EphB2 has prognostic value, as indicated by the association of higher EphB2 expression levels with lower distant metastasis-free survival (DMFS), and the association of lower EphB2 expression levels with poorer relapse-free survival (RFS). We also found that higher EphB2 expression could be a prognostic factor for distant metastasis, specifically in the luminal subtypes of breast cancer. EFNB2 showed a marked correlation between higher expression levels and shorter DMFS. EFNA5 or EFNB1 overexpression is correlated with longer RFS. Increased EFNB1 expression is correlated with longer OS in lymph node (LN)-negative patients and the luminal B subtype. Higher levels of EFNB2 or EFNA5 are significantly correlated with shorter RFS, regardless of LN status. However, while this correlation with shorter RFS is true for EFNB2 in all subtypes except basal, it is also true for EFNA5 in all subtypes except HER2+. The analysis also points to possible predictive value for EphB2. In systemically treated patients who have undergone either endocrine therapy or chemotherapy, we found that higher expression of EphB2 is correlated with better rates of RFS. Bearing in mind the limitations inherent to any mRNA-based profiling method, we complemented our analysis with an immunohistochemical assessment of expression levels of both the EphB2 receptor and cognate ephrin ligands. We found that the latter are significantly more expressed in cancers than in normal tissues, and even more so in invasive and metastatic samples than in ductal carcinoma in situ (DCIS). Finally, in an in vitro cellular model of breast cancer progression, based on H-Ras-transformation of the MCF10A benign mammary cell line, we observed dramatic increases in the mRNA expression of EphB2 receptor and EFNB1 and EFNB2 ligands in transformed and invasive cells in comparison with their benign counterparts. Taken together, these data show the clinical validity of a model whereby EphB2, along with its cognate ephrin ligands, have dual anti- and pro-tumor progression effects. In so doing, they reinforce the necessity of further biological investigations into Ephs and ephrins, prior to using them in targeted therapies.

scholarly journals Serum Long Non-Coding RNAs PVT1, HOTAIR, and NEAT1 as Potential Biomarkers in Egyptian Women with Breast Cancer

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 301
Author(s):  
Amal Ahmed Abd El-Fattah ◽  
Nermin Abdel Hamid Sadik ◽  
Olfat Gamil Shaker ◽  
Amal Mohamed Kamal ◽  
Nancy Nabil Shahin
Keyword(s):  
Breast Cancer ◽  
Logistic Regression ◽  
Cancer Patients ◽  
Breast Cancer Diagnosis ◽  
Serum Levels ◽  
Breast Cancer Patients ◽  
Multivariate Logistic Regression ◽  
Expression Levels ◽  
Non Coding Rnas ◽  
Pai 1

Long non-coding RNAs play an important role in tumor growth, angiogenesis, and metastasis in several types of cancer. However, the clinical significance of using lncRNAs as biomarkers for breast cancer diagnosis and prognosis is still poorly investigated. In this study, we analyzed the serum expression levels of lncRNAs PVT1, HOTAIR, NEAT1, and MALAT1, and their associated proteins, PAI-1, and OPN, in breast cancer patients compared to fibroadenoma patients and healthy subjects. Using quantitative real-time PCR (qRT-PCR), we compared the serum expression levels of the four circulating lncRNAs in patients with breast cancer (n = 50), fibroadenoma (n = 25), and healthy controls (n = 25). The serum levels of PAI-1 and OPN were measured using ELISA. Receiveroperating-characteristic (ROC) analysis and multivariate logistic regression were used to evaluate the diagnostic value of the selected parameters. The serum levels of HOTAIR, PAI-1, and OPN were significantly higher in breast cancer patients compared to controls and fibroadenoma patients. The serum level of PVT1 was significantly higher in breast cancer patients than in the controls, while that of NEAT1 was significantly lower in breast cancer patients compared to controls and fibroadenoma patients. Both ROC and multivariate logistic regression analyses revealed that PAI-1 has the greatest power in discriminating breast cancer from the control, whereas HOTAIR, PAI-1, and OPN have the greatest power in discriminating breast cancer from fibroadenoma patients. In conclusion, our data suggest that the serum levels of PVT1, HOTAIR, NEAT1, PAI-1, and OPN could serve as promising diagnostic biomarkers for breast cancer.

scholarly journals Mapping of Genomic Vulnerabilities in the Post-Translational Ubiquitination, SUMOylation and Neddylation Machinery in Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 833
Author(s):  
Jesús Fuentes-Antrás ◽  
Ana Lucía Alcaraz-Sanabria ◽  
Esther Cabañas Morafraile ◽  
María del Mar Noblejas-López ◽  
Eva María Galán-Moya ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Development ◽  
Gene Mutations ◽  
Complete Response ◽  
Breast Cancer Patients ◽  
Clinical Value ◽  
Luminal A ◽  
Genomic Alterations ◽  
Cancer Hallmarks ◽  
Worse Prognosis

The dysregulation of post-translational modifications (PTM) transversally impacts cancer hallmarks and constitutes an appealing vulnerability for drug development. In breast cancer there is growing preclinical evidence of the role of ubiquitin and ubiquitin-like SUMO and Nedd8 peptide conjugation to the proteome in tumorigenesis and drug resistance, particularly through their interplay with estrogen receptor signaling and DNA repair. Herein we explored genomic alterations in these processes using RNA-seq and mutation data from TCGA and METABRIC datasets, and analyzed them using a bioinformatic pipeline in search of those with prognostic and predictive capability which could qualify as subjects of drug research. Amplification of UBE2T, UBE2C, and BIRC5 conferred a worse prognosis in luminal A/B and basal-like tumors, luminal A/B tumors, and luminal A tumors, respectively. Higher UBE2T expression levels were predictive of a lower rate of pathological complete response in triple negative breast cancer patients following neoadjuvant chemotherapy, whereas UBE2C and BIRC5 expression was higher in luminal A patients with tumor relapse within 5 years of endocrine therapy or chemotherapy. The transcriptomic signatures of USP9X and USP7 gene mutations also conferred worse prognosis in luminal A, HER2-enriched, and basal-like tumors, and in luminal A tumors, respectively. In conclusion, we identified and characterized the clinical value of a group of genomic alterations in ubiquitination, SUMOylation, and neddylation enzymes, with potential for drug development in breast cancer.

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