Prevalence of ESR1 E380Q mutation in tumor tissue and plasma from Japanese breast cancer patients

Abstract Background To comprehensively understand the molecular mechanism of tamoxifen resistance (TamR) acquisition by epigenetically regulated genes, it is essential to identify pivotal genes by genome-wide methylation analysis and verify their function in xenograft animal model and cancer patients. Methods The MCF-7/TamR breast cancer cell line was developed and a genome-wide methylation array was performed. The methylation and expression of ELOVL2 was validated in cultured cells, xenografted tumor tissue, and breast cancer patients by methylation-specific PCR, qRT-PCR, Western blot analysis, and immunohistochemistry. Deregulation of ELOVL2 and THEM4 was achieved using siRNA or generating stable transfectants. Tam sensitivity, cell growth, and apoptosis were monitored by colorimetric and colony formation assay and flow cytometric analysis. Pathway analysis was performed to generate networks for the differentially methylated genes in the MCF-7/TamR cells and for the differentially expressed genes in the ELOVL2-overexpressing cells. Results Genome-wide methylation analysis in the MCF-7/TamR cells identified elongation of very-long chain fatty acid protein 2 (ELOVL2) to be significantly hypermethylated and downregulated, which was further verified in the tumor tissues from TamR breast cancer patients (n = 28) compared with those from Tam-sensitive (TamS) patients (n = 33) (P < 0.001). Immunohistochemical analysis of tissues from cancer patients showed lower expression of ELOVL2 in the TamR than TamS tissues. Growth of the MCF-7/TamR cells overexpressing ELOVL2 was retarded in cell culture and also in xenograft tumor tissue. Strikingly, ELOVL2 attenuated resistance to Tam up to 70% judged by the colorimetric and colony formation assay and xenograft mouse model. ELOVL2 contributed to the recovery of Tam sensitivity by regulating a group of genes in the AKT and ERα signaling pathways, e.g., THEM4, which plays crucial roles in drug resistance. Conclusions ELOVL2 was hypermethylated and downregulated in TamR breast cancer patients compared with TamS patients. ELOVL2 is responsible for the recovery of Tam sensitivity. AKT- and ERα-hubbed networks are pivotal in ELOVL2 signaling, where THEM4 contributes to the relaying ELOVL2 signaling. This study implies that deregulation of a gene in fatty acid metabolism can lead to drug resistance, giving insight into the development of a new therapeutic strategy for drug-resistant breast cancer.

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Genetic Mutations Associated with Hormone-Positive Breast Cancer in Ethiopian Women

10.1101/2020.11.25.20238881 ◽

2020 ◽

Author(s):

Alyssa D. Schwartz ◽

Afua Adusei ◽

Solomon Tsegaye ◽

Christopher A. Moskaluk ◽

Sallie S. Schneider ◽

...

Keyword(s):

Breast Cancer ◽

African Americans ◽

Cancer Patients ◽

Tumor Tissue ◽

Treatment Strategies ◽

Breast Cancer Diagnosis ◽

Breast Cancer Patients ◽

European Descent ◽

Matrix Encoding ◽

New Treatment

AbstractIn Ethiopia, a breast cancer diagnosis is associated with a prognosis significantly worse than that of Europe and the US. Further, patients presenting with breast cancer in Ethiopia are far younger, on average, and patients are typically diagnosed at very late stages, relative to breast cancer patients of European descent. Emerging data suggest that a large proportion of Ethiopian patients have hormone-positive (ER +) breast cancer. This is surprising given 1) the aggressive nature of the disease, 2) that African Americans with breast cancer frequently have triple negative breast cancer (TNBC), and 3) these patients typically receive chemotherapy, not hormone-targeting drugs. To further examine the similarity of Ethiopian breast tumors to those of African Americans or of those of European descent, we sequenced matched normal and tumor tissue from Ethiopian patients from a small pilot collection. We identified mutations in 615 genes across all three patients, unique to the tumor tissue. Across this analysis, we found far more mutations shared between Ethiopian patient tissue and White patients (103) than we did comparing to African Americans (3). Several mutations were found in extracellular matrix encoding genes with known roles in tumor cell growth and metastasis. We suggest future mechanistic studies on this disease focus on these genes first, toward finding new treatment strategies for breast cancer patients in Ethiopia.

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Whole Genome Sequencing in single CTC improves clinical outcome in Her-2 negative breast cancer patients

10.21203/rs.3.rs-15473/v1 ◽

2020 ◽

Author(s):

Bo Yu ◽

Yongping Li ◽

Hao Yuan ◽

Bin Zhang ◽

Xiaofei Jiang ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Tumor Cells ◽

Genome Sequencing ◽

Primary Tumor ◽

Tumor Tissue ◽

Whole Genome ◽

Breast Cancer Patients ◽

Her2 Gene ◽

Her 2

Abstract Background Tumor tissues are usually highly heterogeneous and difficult to characterize which could mislead treatment strategy. Circulating tumor cells (CTCs) represent the most active and invasive tumor cells. This study explored the feasibility of individualized treatment of breast cancer patients based on genome sequencing of single cell CTC. Methods Twenty-four CTCs were identified in three patients with breast cancer. For each patient, one polyploid CTC was captured and on which the whole genome sequencing (WGS) was performed. Based on the histopathological Her-2 status in tumor tissue and the HER2 gene status in WGS results of CTC, we adjusted treatment strategies, and monitored disease progression. Results Patient ID1 and ID2 are Her-2 positive in both primary tumor and HER2 abnormal in the DNA of CTC. In patient ID3, histological examination of primary tumor and liver metastases revealed Her-2 negative, but the WGS analysis of CTC showed that the HER2 gene was amplified and mutated. After adjusting treatment according to the results of CTC sequencing, the liver metastases and pleural effusion were significantly reduced, CTC number and ctDNA burden were decreased. In addition, some potential therapeutic targets and mutations in drug-resistant genes were found. Conclusion The results of CTC sequencing effectively guided treatment of a patient with HER2 gene amplification/mutation in CTC but with Her-2 negative on tumor tissue. CTC sequencing is useful in resolving the heterogeneity of tumors and providing precision medicine for patients.

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Shed HER2 surrogacy evaluation in primary breast cancer patients: a study assessing tumor tissue HER2 expression at both extracellular and intracellular levels

Scandinavian Journal of Clinical and Laboratory Investigation ◽

10.1080/00365513.2019.1600200 ◽

2019 ◽

Vol 79 (4) ◽

pp. 260-267 ◽

Cited By ~ 1

Author(s):

Aline S.C. Fabricio ◽

Silvia Michilin ◽

Matelda Zancan ◽

Valentina Agnolon ◽

Lucia Peloso ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Primary Breast Cancer ◽

Tumor Tissue ◽

Her2 Expression ◽

Breast Cancer Patients

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Correlation of miR-600 with WT1 expression and its potential clinical significance in breast cancer

Personalized Medicine ◽

10.2217/pme-2020-0010 ◽

2021 ◽

Author(s):

Fariba Pishbin ◽

Nasrin Ziamajidi ◽

Roghayeh Abbasalipourkabir ◽

Rezvan Najafi ◽

Maryam Farhadian

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Clinical Significance ◽

Tumor Tissue ◽

Prognostic Biomarker ◽

Clinical Stage ◽

Breast Cancer Patients ◽

Protein Levels ◽

Node Metastasis ◽

Tumor Tissues

Aim: The study aimed to explore miR-600 and WT1 expression and its potential clinical significance in breast cancer. Materials & methods: The expression of miR-600 and WT1 in tumor and non-tumor adjacent tissues in 45 breast cancer patients as well as serum level of miR-600 in these patients and 45 healthy group were analyzed. Results: The expression level of miR-600 in tumor tissue and serum of patients was significantly lower than non-tumor adjacent tissues and serum of controls, respectively, while WT1 mRNA and protein levels were higher in tumor tissues compared with non-tumor adjacent tissues. The miR-600 expression was correlated with lymph node metastasis and clinical stage. Conclusion: The miR-600 acts as tumor suppressor and a diagnostic and prognostic biomarker in breast cancer patients.

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Abstract P1-04-06: Prevalence of PIK3CA mutations in tumor tissue of a consecutive cohort of breast cancer patients (n=700)

10.1158/1538-7445.sabcs14-p1-04-06 ◽

2015 ◽

Author(s):

Martina Vetter ◽

Kristin Reinhardt ◽

Silke Wegener ◽

Juergen Dittmer ◽

Tilmann Lantzsch ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Tumor Tissue ◽

Breast Cancer Patients ◽

Pik3ca Mutations

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