Abstract 1371: Histone lysine trimethylation or acetylation in sporadic breast tumor and matched normal tissue

2014 ◽  
Author(s):  
Dominique J. Gallon-Bernard ◽  
Gaëlle Judes ◽  
Aslihan Dagdemir ◽  
Maureen Echegut ◽  
Seher Karsli-Ceppioglu ◽  
...  
Keyword(s):  
Breast Tumor ◽  
Normal Tissue ◽  
Matched Normal Tissue ◽  
Histone Lysine ◽  
Sporadic Breast Tumor

scholarly journals Identification of Five Cytotoxicity-Related Genes Involved in the Progression of Triple-Negative Breast Cancer

2022 ◽  
Vol 12 ◽  
Author(s):  
Yan Zhang ◽  
Gui-hui Tong ◽  
Xu-Xuan Wei ◽  
Hai-yang Chen ◽  
Tian Liang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cell ◽  
Signaling Pathway ◽  
Therapeutic Efficacy ◽  
Normal Tissue ◽  
R Package ◽  
Rna Seq ◽  
Matched Normal Tissue ◽  
M1 Macrophage ◽  
Key Genes

Background: Breast cancer is one of the deadly tumors in women, and its incidence continues to increase. This study aimed to identify novel therapeutic molecules using RNA sequencing (RNA-seq) data of breast cancer from our hospital.Methods: 30 pairs of human breast cancer tissue and matched normal tissue were collected and RNA sequenced in our hospital. Differentially expressed genes (DEGs) were calculated with raw data by the R package “edgeR”, and functionally annotated using R package “clusterProfiler”. Tumor-infiltrating immune cells (TIICs) were estimated using a website tool TIMER 2.0. Effects of key genes on therapeutic efficacy were analyzed using RNA-seq data and drug sensitivity data from two databases: the Cancer Cell Line Encyclopedia (CCLE) and the Cancer Therapeutics Response Portal (CTRP).Results: There were 2,953 DEGs between cancerous and matched normal tissue, as well as 975 DEGs between primary breast cancer and metastatic breast cancer. These genes were primarily enriched in PI3K-Akt signaling pathway, calcium signaling pathway, cAMP signaling pathway, and cell cycle. Notably, CD8+ T cell, M0 macrophage, M1 macrophage, regulatory T cell and follicular helper T cell were significantly elevated in cancerous tissue as compared with matched normal tissue. Eventually, we found five genes (GALNTL5, MLIP, HMCN2, LRRN4CL, and DUOX2) were markedly corelated with CD8+ T cell infiltration and cytotoxicity, and associated with therapeutic response.Conclusion: We found five key genes associated with tumor progression, CD8+ T cell and therapeutic efficacy. The findings would provide potential molecular targets for the treatment of breast cancer.

Comprehensive molecular and genomic characterization of pancreatic tropism in metastatic renal cell carcinoma.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 633-633 ◽  
Author(s):  
Nirmish Singla ◽  
Jacob Choi ◽  
Oreoluwa Onabolu ◽  
Layton Woolford ◽  
Christina Stevens ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Normal Tissue ◽  
Pancreatic Metastasis ◽  
Matched Normal Tissue ◽  
Pancreatic Metastases ◽  
Metastatic Sites ◽  
Pdx Models

633 Background: Patients with metastatic renal cell carcinoma (mRCC) involving the pancreas have been shown to exhibit a relatively indolent course, yet the biologic explanation is unclear. We sought to characterize the genomic landscape of patients with mRCC harboring pancreatic metastases to identify molecular drivers of pancreatic tropism. Methods: mRCC patients harboring pancreatic metastases from UTSW and Cleveland Clinic were identified. Clinicopathologic data and oncologic outcomes were analyzed. Samples were obtained from primary tumors, metastatic sites (including pancreatic or other distant metastases), and matched normal tissue. Whole exome (WES) and RNA sequencing of tumors was conducted. Patient-derived xenograft (PDX) models were generated from a subset of patients, and the engrafted tumors were analyzed. Results: 31 mRCC patients with pancreatic metastases were included with 54 tumor samples derived from the primary tumor or thrombus (24), pancreatic metastasis (21), or other metastatic sites (9). Median follow-up was 101 months. Clinicopathologic characteristics were similar between the two institutional cohorts, and all but one patient were favorable or intermediate IMDC risk. All patients had clear cell histology. 8 patients (26%) were metastatic at diagnosis, and median time to metastasis in the remaining patients was 74 months (IQR 32-120). Overall (OS) and cancer-specific (CSS) survival did not vary by IMDC risk group. Morphologically, tumors largely displayed low-grade acinar patterns. WES with matched normal tissue and RNAseq were completed with adequate quality for 48 and 30 samples, respectively. 14 PDX lines were generated, of which 5 (36%) engrafted stably (≥2 passages). WES from 2 tumorgraft specimens revealed preservation of specific mutations in the corresponding human samples. Conclusions: mRCC patients with pancreatic metastases exhibit remarkably favorable survival outcomes. The relatively indolent biology of these tumors is reflected histologically and genomically and can be recapitulated in PDX models. Understanding tumor heterogeneity may help refine prognostic models for mRCC and hold implications for improved personalization of therapy.

scholarly journals Gene expression profiling of multiple leiomyomata uteri and matched normal tissue from a single patient

2009 ◽  
Vol 91 (6) ◽  
pp. 2650-2663 ◽  
Author(s):  
Irina K. Dimitrova ◽  
Jennifer K. Richer ◽  
Michael C. Rudolph ◽  
Nicole S. Spoelstra ◽  
Elaine M. Reno ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Normal Tissue ◽  
Single Patient ◽  
Matched Normal Tissue

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

2013 ◽  
Vol 142 (2) ◽  
pp. 365-380 ◽  
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

Levels of Oxidative Damage in Thyroid Neoplasia

2008 ◽  
Vol 139 (2_suppl) ◽  
pp. P91-P91
Author(s):  
Orla G Young ◽  
Jacintha N O'Sullivan ◽  
Rohana O'Connell ◽  
Crotty Thomas ◽  
Aongus J. Curran
Keyword(s):  
Oxidative Damage ◽  
Normal Tissue ◽  
Thyroid Neoplasms ◽  
Tissue Microarrays ◽  
Early Event ◽  
P Values ◽  
Matched Normal Tissue ◽  
Normal Tissues ◽  
Thyroid Neoplasia ◽  
Subsequent Risk

Problem To assess levels of oxidative damage: DNA adduct (8 oxo dG) and lipid peroxidation (4HNE) in follicular carcinomas (FTC), papillary carcinomas (PTC) and follicular adenomas (FTA) and their corresponding matched normal tissue. Methods Using tissue microarrays and immunohistochemistry, we examined expression levels of nuclear and cytoplasmic (mitochondrial) 8 oxo dG and 4HNE in matched tumor and normal tissues from 16 FTC's, 15 PTC's and 39 FTA's. Results There were higher levels of mitochondrial 8 oxo dG expression in the FTA, FTC and PTC tissue compared to matched normal tissue (p values <0.001, <0.001, <0.03, respectively). This trend remained significant for the levels of mitochondrial 4HNE expression in these groups. (All p values < 0.01.) The levels of nuclear 4HNE expression were elevated in FTA and FTC compared to matched normal tissue (p values <0.001, <0.01, respectively). In contrast, the levels of nuclear 8 oxo dG expression was only statistically significant in the FTA group compared to matched normal tissue. Comparing all three groups to each other, there were higher levels of nuclear 8 oxo dG expression in FTA compared to FTC (p<0.01). This difference was not detected for 4HNE expression. Conclusion Oxidative stress is a key feature of benign and malignant thyroid neoplasms. Interestingly, levels of oxidative damage are higher in adenoma compared to the carcinoma groups. Significance The higher levels of oxidative damage in thyroid adenoma compared to carcinoma groups indicates the accumulation of this damage is an early event which could promote further genomic instability with subsequent risk of mutational events.

scholarly journals Epigenetic field cancerization in breast cancer using subject-matched tumor, ipsilateral-normal, and contralateral-normal tissues

2019 ◽  
Author(s):  
Meghan E. Muse ◽  
Alexander J. Titus ◽  
Lucas A. Salas ◽  
Owen M. Wilkins ◽  
Chelsey Mullen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Breast Tumor ◽  
Normal Tissue ◽  
Tumor Tissue ◽  
Cpg Islands ◽  
Normal Breast ◽  
Field Cancerization ◽  
Breast Carcinogenesis ◽  
Normal Tissues

AbstractBackgroundEmerging work has demonstrated that histologically normal (non-tumor) tissue adjacent to breast tumor tissue shows evidence of molecular alterations related to tumorigenesis, referred to as field cancerization effects. Although changes in DNA methylation are known to occur early in breast carcinogenesis and the landscape of breast tumor DNA methylation is profoundly altered compared with normal tissue, there have been limited efforts to identify DNA methylation field cancerization effects in histologically normal breast tissue adjacent to tumor.MethodsMatched tumor, histologically normal tissue of the ipsilateral breast (ipsilateral-normal), and histologically normal tissue of the contralateral breast (contralateral-normal) were obtained from nine women undergoing bilateral mastectomy. Laser capture microdissection was used to select breast epithelial cells from normal tissues, and neoplastic cells from tumor specimens for genome-scale measures of DNA methylation with the Illumina HumanMethylationEPIC array.ResultsWe identified substantially more CpG loci that were differentially methylated between contralateral-normal breast and tumor tissue (63,271 CpG loci q < 0.01), than between ipsilateral-normal tissue and tumor (38,346 CpG loci q < 0.01). In addition, we identified differential methylation in ipsilateral-normal relative to contralateral-normal tissue (9,562 CpG loci p < 0.01). Hypomethylated loci in ipsilateral normal relative to contralateral were significantly enriched for breast cancer-relevant transcription factor binding sites including those for ESR1, FoxA1, and GATA3. Hypermethylated loci in ipsilateral-normal relative to contralateral-normal tissue were significantly enriched for CpG island shore regions.ConclusionsOur results indicate that early hypermethylation events in breast carcinogenesis are more likely to occur in the regions immediately surrounding CpG islands than CpG islands per se, reflecting a field effect of the tumor on surrounding histologically normal tissue. This work offers an opportunity to focus investigations of early DNA methylation alterations in breast carcinogenesis and potentially develop epigenetic biomarkers of disease risk.

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