Non-microarray DNA differential methylation screening in breast cancer

Background Paclitaxel is an important chemotherapeutic agent for the treatment of breast cancer. Paclitaxel-induced peripheral neuropathy (PIPN) is a major dose-limiting toxicity that can persist into survivorship. While not all survivors develop PIPN, for those who do, it has a substantial negative impact on their functional status and quality of life. No interventions are available to treat PIPN. In our previous studies, we identified that the HIF-1 signaling pathway (H1SP) was perturbed between breast cancer survivors with and without PIPN. Preclinical studies suggest that the H1SP is involved in the development of bortezomib-induced and diabetic peripheral neuropathy, and sciatic nerve injury. The purpose of this study was to identify H1SP genes that have both differential methylation and differential gene expression between breast cancer survivors with and without PIPN. Methods A multi-staged integrated analysis was performed. In peripheral blood, methylation was assayed using microarray and gene expression was assayed using RNA-seq. Candidate genes in the H1SP having both differentially methylation and differential expression were identified between survivors who received paclitaxel and did (n = 25) and did not (n = 25) develop PIPN. Then, candidate genes were evaluated for differential methylation and differential expression in public data sets of preclinical models of PIPN and sciatic nerve injury. Results Eight candidate genes were identified as both differential methylation and differential expression in survivors. Of the eight homologs identified, one was found to be differential expression in both PIPN and “normal” mice dorsal root ganglia; three were differential methylation in sciatic nerve injury versus sham rats in both pre-frontal cortex and T-cells; and two were differential methylation in sciatic nerve injury versus sham rats in the pre-frontal cortex. Conclusions This study is the first to evaluate for methylation in cancer survivors with chronic PIPN. The findings provide evidence that the expression of H1SP genes associated with chronic PIPN in cancer survivors may be regulated by epigenetic mechanisms and suggests genes for validation as potential therapeutic targets.

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Differential methylation relative to breast cancer subtype and matched normal tissue reveals distinct patterns

Breast Cancer Research and Treatment ◽

10.1007/s10549-013-2738-0 ◽

2013 ◽

Vol 142 (2) ◽

pp. 365-380 ◽

Cited By ~ 23

Author(s):

Sabrina A. Bardowell ◽

Joel Parker ◽

Cheng Fan ◽

Jamie Crandell ◽

Charles M. Perou ◽

...

Keyword(s):

Breast Cancer ◽

Normal Tissue ◽

Breast Cancer Subtype ◽

Differential Methylation ◽

Matched Normal Tissue ◽

Cancer Subtype

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Differential methylation hybridization profiling identifies involvement of STAT1-mediated pathways in breast cancer

International Journal of Oncology ◽

10.3892/ijo.2011.1075 ◽

2011 ◽

Author(s):

Han-Sung Kang

Keyword(s):

Breast Cancer ◽

Differential Methylation ◽

Differential Methylation Hybridization

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Vertical and Horizontal DNA Differential Methylation Analysis for Predicting Breast Cancer

IEEE Access ◽

10.1109/access.2018.2871027 ◽

2018 ◽

Vol 6 ◽

pp. 53533-53545 ◽

Cited By ~ 1

Author(s):

Abdulmajid F. Al-Juniad ◽

Talal S. Qaid ◽

Mohammad Yahya H. Al-Shamri ◽

Mahdi H.A. Ahmed ◽

Abeer A. Raweh

Keyword(s):

Breast Cancer ◽

Differential Methylation ◽

Methylation Analysis ◽

Differential Methylation Analysis

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Physical Activity and Differential Methylation of Breast Cancer Genes Assayed from Saliva: A Preliminary Investigation

Annals of Behavioral Medicine ◽

10.1007/s12160-012-9411-4 ◽

2012 ◽

Vol 45 (1) ◽

pp. 89-98 ◽

Cited By ~ 29

Author(s):

Angela D. Bryan ◽

Renee E. Magnan ◽

Ann E. Caldwell Hooper ◽

Nicole Harlaar ◽

Kent E. Hutchison

Keyword(s):

Breast Cancer ◽

Physical Activity ◽

Preliminary Investigation ◽

Differential Methylation ◽

Cancer Genes ◽

Breast Cancer Genes

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Survival of breast cancer patients treated with cyclophosphamide depending on the expression of the LTB4R leukotriene receptor gene in tumor tissue

Nauchno-prakticheskii zhurnal «Medicinskaia genetika» ◽

10.25557/2073-7998.2020.06.18-19 ◽

2020 ◽

pp. 18-19

Author(s):

А.И. Калинкин ◽

В.О. Сигин ◽

В.В. Стрельников ◽

А.С. Танас

Keyword(s):

Breast Cancer ◽

Tumor Tissue ◽

Triple Negative ◽

Cpg Island ◽

Receptor Gene ◽

Ectopic Expression ◽

Differential Methylation ◽

Breast Cancer Patients ◽

Genome Wide ◽

Leukotriene Receptor

По результатам широкогеномного скрининга дифференциального метилирования в образцах рака молочной железы (РМЖ) нами было обнаружено аномальное деметилирование CpG-островка гена лейкотриенового рецептора LTB4R, которое может приводить к его эктопической экспрессии. В настоящей работе мы использовали данные, полученные при анализе 1083 образцов РМЖ в рамках проекта TCGA-BRCA, для определения влияния экспрессии LTB4R на эффективность лечения циклофосфамидом. Анализ кривых выживаемости пациенток с трижды-негативным (ТН) РМЖ с высокой экспрессией LTB4R в опухолях показал увеличение общей выживаемости при лечении циклофосфамидом (p<0,05). Для LumB подтипа РМЖ эффект циклофосфамида не зависел от экспрессии LTB4R. Полученные результаты расширяют возможности персонализации терапии РМЖ. Based on the results of genome-wide screening of differential methylation in breast cancer samples (BC), we have identified abnormal demethylation of the LTB4R leukotriene receptor gene CpG island, which can lead to its ectopic expression. In this paper, we used the data obtained for 1083 BC samples under the TCGA-BRCA project to determine impact of LTB4R expression on the effectiveness of treatment with cyclophosphamide. Analysis of survival curves for patients with triple-negative (TN) breast cancer and high expression of LTB4R showed an increase in overall survival of patients treated with cyclophosphamide (p <0.05). For LumB BC subtype, the effect of cyclophosphamide was not dependent on LTB4R expression. The results obtained expand the possibilities of personalizing BC therapy.

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A Pilot Study Using a Multistaged Integrated Analysis of Gene Expression and Methylation to Evaluate Mechanisms for Evening Fatigue in Women Who Received Chemotherapy for Breast Cancer

Biological Research For Nursing ◽

10.1177/1099800418823286 ◽

2019 ◽

Vol 21 (2) ◽

pp. 142-156 ◽

Cited By ~ 4

Author(s):

Elena Flowers ◽

Annesa Flentje ◽

Jon Levine ◽

Adam Olshen ◽

Marilyn Hammer ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Pilot Study ◽

Molecular Mechanisms ◽

Methylation Status ◽

Differential Methylation ◽

Integrated Analysis ◽

Common Symptom ◽

Fatigue Severity ◽

Very High

Context: Fatigue is the most common symptom associated with cancer and its treatment. Investigation of molecular mechanisms associated with fatigue may identify new therapeutic targets. Objective: The objective of this pilot study was to evaluate the relationships between gene expression and methylation status and evening fatigue severity in women with breast cancer who received chemotherapy. Methods: Latent class analysis (LCA) was used to identify evening fatigue phenotypes. In this analysis, the lowest (i.e., moderate, n = 7) and highest (i.e., very high, n = 29) fatigue-severity classes identified using LCA were analyzed via two stages. First, a total of 32,609 transcripts from whole blood were evaluated for differences in expression levels between the classes. Next, 637 methylation sites located within the putative transcription factor binding sites for those genes demonstrating differential expression were evaluated for differential methylation state between the classes. Results: A total of 89 transcripts in 75 unique genes were differentially expressed between the moderate (the lowest fatigue-severity class identified) and very high evening fatigue classes. In addition, 23 differentially methylated probes and three differentially methylated regions were found between the moderate and very high evening fatigue classes. Conclusions: Using a multistaged integrated analysis of gene expression and methylation, differential methylation was identified in the regulatory regions of genes associated with previously hypothesized mechanisms for fatigue, including inflammation, immune function, neurotransmission, circadian rhythm, skeletal muscle energy, carbohydrate metabolism, and renal function as well as core biological processes including gene transcription and the cell-cycle regulation.

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Virus-Like Particles in a Human Breast Cancer: Structural Similarity to Previously Reported Particles

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100072332 ◽

1973 ◽

Vol 31 ◽

pp. 378-379

Author(s):

G. Kasnic ◽

S. E. Stewart ◽

C. Urbanski

Keyword(s):

Breast Cancer ◽

Biological Activity ◽

Human Breast Cancer ◽

Osteogenic Sarcoma ◽

Human Tumor ◽

Structural Similarity ◽

Cell Tumor ◽

Human Breast ◽

Human Tumor Cell ◽

Type Particle

We have reported the maturation of an intracisternal A-type particle in murine plasma cell tumor cultures and three human tumor cell cultures (rhabdomyosarcoma, lung adenocarcinoma, and osteogenic sarcoma) after IUDR-DMSO activation. In all of these studies the A-type particle seems to develop into a form with an electron dense nucleoid, presumably mature, which is also intracisternal. A similar intracisternal A-type particle has been described in leukemic guinea pigs. Although no biological activity has yet been demonstrated for these particles, on morphologic grounds, and by the manner in which they develop within the cell, they may represent members of the same family of viruses.

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Further Ultrastructural Observations on Metastatic Nodules of Human Breast Cancer

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010010086x ◽

1968 ◽

Vol 26 ◽

pp. 224-225

Author(s):

John L. Swedo ◽

R. W. Talley ◽

John H. L. Watson

Keyword(s):

Breast Cancer ◽

Human Breast Cancer ◽

Estrogen Therapy ◽

Specimen Preparation ◽

Human Breast ◽

Autophagic Vacuoles ◽

Previous Communication ◽

Linear Profiles ◽

Metastatic Nodule

Since the report, which described the ultrastructure of a metastatic nodule of human breast cancer after estrogen therapy, additional ultrastructural observations, including some which are correlative with pertinent findings in the literature concerning mycoplasmas, have been recorded concerning the same subject. Specimen preparation was identical to that in.The mitochondria possessed few cristae, and were deteriorated and vacuolated. They often contained particulates and fibrous structures, sometimes arranged in spindle-shaped bundles, Fig. 1. Another apparent aberration was the occurrence, Fig. 2 (arrows) of linear profiles of what seems to be SER, which lie between layers of RER, and are often recognizably continuous with them.It was noted that the structure of the round bodies, interpreted as within autophagic vacuoles in the previous communication, and of vesicular bodies, described morphologically closely resembled those of some mycoplasmas. Specifically, they simulated or reflected the various stages of replication reported for mycoplasmas grown on solid nutrient. Based on this observation, they are referred to here as “mycoplasma-like” structures, in anticipation of confirmatory evidence from investigations now in progress.

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