scholarly journals Basal cytokeratins in breast tumours among BRCA1, BRCA2and mutation-negative breast cancer families

2008 ◽  
Vol 10 (1) ◽  
Author(s):  
Hannaleena Eerola ◽  
Mira Heinonen ◽  
Päivi Heikkilä ◽  
Outi Kilpivaara ◽  
Anitta Tamminen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Tumours ◽  
Basal Cytokeratins

scholarly journals The molecular landscape of Asian breast cancers reveals clinically relevant population-specific differences

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jia-Wern Pan ◽  
Muhammad Mamduh Ahmad Zabidi ◽  
Pei-Sze Ng ◽  
Mei-Yee Meng ◽  
Siti Norhidayu Hasan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Somatic Mutations ◽  
Checkpoint Inhibitors ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Breast Tumours ◽  
Different Populations ◽  
Caucasian Women ◽  
Molecular Landscape ◽  
Immune Score

AbstractMolecular profiling of breast cancer has enabled the development of more robust molecular prognostic signatures and therapeutic options for breast cancer patients. However, non-Caucasian populations remain understudied. Here, we present the mutational, transcriptional, and copy number profiles of 560 Malaysian breast tumours and a comparative analysis of breast cancers arising in Asian and Caucasian women. Compared to breast tumours in Caucasian women, we show an increased prevalence of HER2-enriched molecular subtypes and higher prevalence of TP53 somatic mutations in ER+ Asian breast tumours. We also observe elevated immune scores in Asian breast tumours, suggesting potential clinical response to immune checkpoint inhibitors. Whilst HER2-subtype and enriched immune score are associated with improved survival, presence of TP53 somatic mutations is associated with poorer survival in ER+ tumours. Taken together, these population differences unveil opportunities to improve the understanding of this disease and lay the foundation for precision medicine in different populations.

scholarly journals Ribosomal RNA 2′O-methylation as a novel layer of inter-tumour heterogeneity in breast cancer

NAR Cancer ◽  
2020 ◽  
Vol 2 (4) ◽  
Author(s):  
Virginie Marcel ◽  
Janice Kielbassa ◽  
Virginie Marchand ◽  
Kundhavai S Natchiar ◽  
Hermes Paraqindes ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ribosomal Rna ◽  
Large Scale ◽  
Gene Expression Regulation ◽  
Molecular Signature ◽  
Translation Control ◽  
Breast Tumours ◽  
Cellular Models ◽  
Additional Layer ◽  
Tumour Biology

Abstract Recent epitranscriptomics studies unravelled that ribosomal RNA (rRNA) 2′O-methylation is an additional layer of gene expression regulation highlighting the ribosome as a novel actor of translation control. However, this major finding lies on evidences coming mainly, if not exclusively, from cellular models. Using the innovative next-generation RiboMeth-seq technology, we established the first rRNA 2′O-methylation landscape in 195 primary human breast tumours. We uncovered the existence of compulsory/stable sites, which show limited inter-patient variability in their 2′O-methylation level, which map on functionally important sites of the human ribosome structure and which are surrounded by variable sites found from the second nucleotide layers. Our data demonstrate that some positions within the rRNA molecules can tolerate absence of 2′O-methylation in tumoral and healthy tissues. We also reveal that rRNA 2′O-methylation exhibits intra- and inter-patient variability in breast tumours. Its level is indeed differentially associated with breast cancer subtype and tumour grade. Altogether, our rRNA 2′O-methylation profiling of a large-scale human sample collection provides the first compelling evidence that ribosome variability occurs in humans and suggests that rRNA 2′O-methylation might represent a relevant element of tumour biology useful in clinic. This novel variability at molecular level offers an additional layer to capture the cancer heterogeneity and associates with specific features of tumour biology thus offering a novel targetable molecular signature in cancer.

scholarly journals EMT cells increase breast cancer metastasis via paracrine GLI activation in neighbouring tumour cells

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Deepika Neelakantan ◽  
Hengbo Zhou ◽  
Michael U. J. Oliphant ◽  
Xiaomei Zhang ◽  
Lukas M. Simon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Tumour Cells ◽  
Human Breast ◽  
Breast Tumours ◽  
Cancer Models ◽  
Pdx Models

Abstract Recent fate-mapping studies concluded that EMT is not required for metastasis of carcinomas. Here we challenge this conclusion by showing that these studies failed to account for possible crosstalk between EMT and non-EMT cells that promotes dissemination of non-EMT cells. In breast cancer models, EMT cells induce increased metastasis of weakly metastatic, non-EMT tumour cells in a paracrine manner, in part by non-cell autonomous activation of the GLI transcription factor. Treatment with GANT61, a GLI1/2 inhibitor, but not with IPI 926, a Smoothened inhibitor, blocks this effect and inhibits growth in PDX models. In human breast tumours, the EMT-transcription factors strongly correlate with activated Hedgehog/GLI signalling but not with the Hh ligands. Our findings indicate that EMT contributes to metastasis via non-cell autonomous effects that activate the Hh pathway. Although all Hh inhibitors may act against tumours with canonical Hh/GLI signalling, only GLI inhibitors would act against non-canonical EMT-induced GLI activation.

scholarly journals Protein arginine methyltransferase 6-dependent gene expression and splicing: association with breast cancer outcomes

2012 ◽  
Vol 19 (4) ◽  
pp. 509-526 ◽  
Author(s):  
Dennis H Dowhan ◽  
Matthew J Harrison ◽  
Natalie A Eriksson ◽  
Peter Bailey ◽  
Michael A Pearen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Alternative Splicing ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Gene Expression Signature ◽  
Human Breast ◽  
Arginine Methyltransferase ◽  
Breast Tumours

Protein arginine methyltransferase-6 (PRMT6) regulates steroid-dependent transcription and alternative splicing and is implicated in endocrine system development and function, cell death, cell cycle, gene expression and cancer. Despite its role in these processes, little is known about its function and cellular targets in breast cancer. To identify novel gene targets regulated by PRMT6 in breast cancer cells, we used a combination of small interfering RNA and exon-specific microarray profilingin vitrocoupled toin vivovalidation in normal breast and primary human breast tumours. This approach, which allows the examination of genome-wide changes in individual exon usage and total transcript levels, demonstrated thatPRMT6knockdown significantly affected i) the transcription of 159 genes and ii) alternate splicing of 449 genes. ThePRMT6-dependent transcriptional and alternative splicing targets identifiedin vitrowere validated in human breast tumours. Using the list of genes differentially expressed between normal andPRMT6knockdown cells, we generated aPRMT6-dependent gene expression signature that provides an indication of PRMT6 dysfunction in breast cancer cells. Interrogation of several well-studied breast cancer microarray expression datasets with thePRMT6gene expression signature demonstrated that PRMT6 dysfunction is associated with better overall relapse-free and distant metastasis-free survival in the oestrogen receptor (ER (ESR1)) breast cancer subgroup. These results suggest that dysregulation ofPRMT6-dependent transcription and alternative splicing may be involved in breast cancer pathophysiology and the molecular consequences identifying a unique and informative biomarker profile.

Prognostic value of Ki67 analysed by cytology or histology in primary breast cancer

2018 ◽  
Vol 71 (9) ◽  
pp. 787-794 ◽  
Author(s):  
Stephanie Robertson ◽  
Gustav Stålhammar ◽  
Eva Darai-Ramqvist ◽  
Mattias Rantalainen ◽  
Nicholas P Tobin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Overall Survival ◽  
Survival Data ◽  
Prognostic Value ◽  
Molecular Subtype ◽  
Axillary Lymph Node Metastasis ◽  
Axillary Lymph ◽  
Poor Overall Survival ◽  
Breast Tumours

AimsThe accuracy of biomarker assessment in breast pathology is vital for therapy decisions. The therapy predictive and prognostic biomarkers oestrogen receptor (ER), progesterone receptor, HER2 and Ki67 may act as surrogates to gene expression profiling of breast cancer. The aims of this study were to investigate the concordance of consecutive biomarker assessment by immunocytochemistry on preoperative fine-needle aspiration cytology versus immunohistochemistry (IHC) on the corresponding resected breast tumours. Further, to investigate the concordance with molecular subtype and correlation to stage and outcome.MethodsTwo retrospective cohorts comprising 385 breast tumours with clinicopathological data including gene expression-based subtype and up to 10-year overall survival data were evaluated.ResultsIn both cohorts, we identified a substantial variation in Ki67 index between cytology and histology and a switch between low and high proliferation within the same tumour in 121/360 cases. ER evaluations were discordant in only 1.5% of the tumours. From cohort 2, gene expression data with PAM50 subtype were used to correlate surrogate subtypes. IHC-based surrogate classification could identify the correct molecular subtype in 60% and 64% of patients by cytology (n=63) and surgical resections (n=73), respectively. Furthermore, high Ki67 in surgical resections but not in cytology was associated with poor overall survival and higher probability for axillary lymph node metastasis.ConclusionsThis study shows considerable differences in the prognostic value of Ki67 but not ER in breast cancer depending on the diagnostic method. Furthermore, our findings show that both methods are insufficient in predicting true molecular subtypes.

scholarly journals TSH receptor antibodies in breast cancer and benign breast disease: a hospital based study

2017 ◽  
Vol 4 (12) ◽  
pp. 3989
Author(s):  
Jawahar Krishnaswamy ◽  
Reshma Sattar
Keyword(s):  
Breast Cancer ◽  
Prognostic Markers ◽  
Breast Disease ◽  
Tsh Receptor ◽  
Breast Diseases ◽  
Breast Tumours ◽  
Receptor Antibody ◽  
Tsh Receptor Antibody ◽  
Receptor Antibodies ◽  
Tsh Receptor Antibodies

Background: Associations between breast cancer, benign breast tumours and thyroid disorders are reported in numerous studies. Relationship between thyroperoxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb), and breast cancer have been previously demonstrated. However, no analysis has been performed concerning an association between thyrotropin (TSH) receptor antibodies (TSHRAb) and breast cancer. The aim of the study was to evaluate the presence of TSH Receptor antibodies in women with breast cancer or benign breast tumours, and to analyze a possible relationship between TSH Receptor antibodies, and these two groups of breast diseases with emphasis to laboratory findings.Methods: Clinical and laboratory details of 87 women hospitalized were prospectively analyzed, using an Post hoc Tukey HSD for normally distributed continuous data, chi-square test for comparison.Results: TSH Receptor antibody levels in breast cancer was statistically significant. We observed TSHRAb more frequently in patients with breast cancer. We found that TSHRAb is the only variable possessing as a prognostic marker for breast cancer.Conclusions: The present study indicates that the serum levels of TSH Receptor Antibody are significant higher in patients with Breast cancer. These results have implications not only for the screening of patients but also for the development of new prognostic markers. Further high-quality prospective studies are needed to explore whether TSH Receptor Antibodies are potential prognostic markers for patients with Breast cancer.

scholarly journals Metabolic Flexibility Is a Determinant of Breast Cancer Heterogeneity and Progression

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4699
Author(s):  
Marina Fukano ◽  
Morag Park ◽  
Geneviève Deblois
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Metabolic Flexibility ◽  
Extrinsic Factors ◽  
Breast Tumours ◽  
Cancer Heterogeneity ◽  
Energy Demands ◽  
Metabolic States ◽  
Metabolic Heterogeneity ◽  
High Level

Breast cancer progression is characterized by changes in cellular metabolism that contribute to enhanced tumour growth and adaptation to microenvironmental stresses. Metabolic changes within breast tumours are still poorly understood and are not as yet exploited for therapeutic intervention, in part due to a high level of metabolic heterogeneity within tumours. The metabolic profiles of breast cancer cells are flexible, providing dynamic switches in metabolic states to accommodate nutrient and energy demands and further aggravating the challenges of targeting metabolic dependencies in cancer. In this review, we discuss the intrinsic and extrinsic factors that contribute to metabolic heterogeneity of breast tumours. Next, we examine how metabolic flexibility, which contributes to the metabolic heterogeneity of breast tumours, can alter epigenetic landscapes and increase a variety of pro-tumorigenic functions. Finally, we highlight the difficulties in pharmacologically targeting the metabolic adaptations of breast tumours and provide an overview of possible strategies to sensitize heterogeneous breast tumours to the targeting of metabolic vulnerabilities.

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