Abstract 3169: The benefits and burdens of assaying matched normal tissue when sequencing cancer genomes

2016 ◽  
Author(s):  
Elena Helman ◽  
Michael J. Clark ◽  
Ravi Alla ◽  
Sean M. Boyle ◽  
Shujun Luo ◽  
...  
Keyword(s):  
Normal Tissue ◽  
Matched Normal Tissue ◽  
Cancer Genomes

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.

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

Abstract 5293: A method to identify somatic mutations from tumor samples in the absence of matched normal tissue

2018 ◽  
Author(s):  
Lijing Yao ◽  
Preeti Lal ◽  
Li-Tai Fang ◽  
John Lee ◽  
John Palma ◽  
...  
Keyword(s):  
Normal Tissue ◽  
Somatic Mutations ◽  
Matched Normal Tissue

Integrated comprehensive high-throughput kinomics profiling and whole exome sequencing of penile squamous cell cancer (PSCC).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 383-383
Author(s):  
Amitkumar N. Mehta ◽  
Christopher Willey ◽  
Michael Crowley ◽  
Joshua Anderson ◽  
Dongquan Chen ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Squamous Cell ◽  
Normal Tissue ◽  
Squamous Cell Cancer ◽  
Cell Cancer ◽  
The Cancer Genome Atlas ◽  
Exome Capture ◽  
Matched Normal Tissue ◽  
Whole Exome

383 Background: Molecular drivers in penile squamous cell cancer (PSCC), an orphan malignancy, remain unclear. The Cancer Genome Atlas (TCGA) is not studying PSCC and the Catalogue of Somatic Mutations in Cancer (COSMIC) investigators have reported only targeted analyses of PSCC. We report the first integrated analyses of comprehensive kinomics and whole exome sequencing (seq) in tumors from patients (pts) with PSCC . Methods: We performed integrated functional kinomics profiling and comprehensive exome-seq of two frozen tissue samples from men with PSCC with a matched normal tissue procured from the Cooperative Human Tissue Network (CHTN). Kinomic profiling was performed using the PamStation 12 high-content phospho-peptide substrate microarray system (PamGene International). The protein tyrosine kinome and serine/threonine kinome PamChips were used to measure global kinase activity by detecting phosphorylation of various peptides through FITC-labeled antibodies. Upstream kinase prediction was performed using a scoring algorithm that incorporates the phosphonet database (www.phosphonet.ca). Exome capture was performed with the Agilent SureSelect v5 kit and whole exome-seq was done on the Illumina HiSeq2000 with paired end 100bp chemistry. Results: In the single patient, paired kinomics analysis comparing the tumor sample to adjacent normal tissue, the HER family (EGFR, ERBB2, 3 and 4), AXL, TYRO3 and SYK kinases were the most active. When combining the two tumors in an unpaired analysis against the normal sample, the HER (EGFR, ERBB2, 3 and 4), MER, FRK, and FAK, kinases showed increased activity. When comparing whole exome-seq of the two PSCC samples with normal, among the affected genes were CCDC181, ZNF717, MUC4, HGC6.3, NOTCH1, STK11, SIRPB1, SKA3, PDE6B, FAT1, CACNA2D1, USP17L11, MNT, and CEP89. We are evaluating 10 PSCC tumors and matched normal tissue by kinomics and whole exome-seq and will present these complete data and analysis at the conference. Conclusions: In our preliminary analysis of pts that underwent the first reported integrated kinomics and whole exome-seq performed in PSCC, we identified multiple potential therapeutic targets in tumors.

WINTHER: An international study to select rational therapeutics based on the analysis of matched tumor and normal biopsies in subjects with advanced malignancies.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS11625-TPS11625 ◽  
Author(s):  
Jean-Charles Soria ◽  
Jordi Rodon Ahnert ◽  
Raanan Berger ◽  
Wilson H. Miller ◽  
Irene Brana ◽  
...  
Keyword(s):  
Normal Tissue ◽  
Metastatic Cancer ◽  
Performance Status ◽  
Randomized Study ◽  
International Study ◽  
Treatment Decision ◽  
Progression Free Survival ◽  
Study Endpoint ◽  
Matched Normal Tissue ◽  
Prior Therapy

TPS11625 Background: Today, personalized cancer medicine implies matching the patient’s tumor genomic characteristics with molecularly and immune targeted agents. Although there are an increasing number of DNA aberrations that can now be matched to a cognate therapy, some patients do not display such druggable oncogene drivers. Methods: WINTHER is an open non-randomized study involving 6 cancer centers in France, Spain, Israel, Canada and USA applying genomic and also transcriptomic assays to guide treatment decisions. The novelty of the WINTHER approach lies in the use of tumor and matched normal tissue biopsies together and an algorithm for predicting efficacy of therapies. The aim is to provide a rational therapeutic choice for all of the patients enrolled in the study whether or not they harbor actionable DNA alterations. The study endpoint is the comparison of the progression-free-survival (PFS) under the WINTHER selected therapy to the PFS of the last therapeutic line. Patients included have refractory metastatic cancer of any histological type, with at least one prior therapeutic regimen and performance status of 0 to 1. Patients who have received a matched treatment based on a molecular anomaly as their immediate prior therapy were excluded. After consent, patients undergo a tumor and histologically-matched normal tissue biopsy. Extracted DNA and RNA of both tumor and normal from frozen tissues at the local center under common standard operating procedures are sent to centralized laboratories for omics investigations. DNA is investigated at Foundation Medicine Inc. and RNA at Gustave Roussy using Agilent technology. For RNA, the WINTHER algorithm is applied on the differential RNA expression data between tumor and normal tissues and establishes the list of drugs with the presumed higher score of efficacy for each patient. Patients with actionable genomic events enter in ARM A, and patients without any druggable anomaly of the DNA enter in ARM B and are treated using the WINTHER algorithm RNA-based treatment decision tool. To date, the trial has recruited 303 patients. Clinical trial information: NCT01856296.

Sign in / Sign up

Export Citation Format

Share Document