bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2203: Integrative analysis for efficient candidate oncogene discovery in cancer cell lines
Authors: Yee Andrew J. , Wittner Ben S. , Gentry Jeff , Mahoney Crystal , McCutcheon Kaitlin , Singh Anurag , Greninger Patricia , Ma Xiao-Jun , Erlander Mark G. , Sharma Sreenath V. , Haber Daniel A. , Shioda Toshi , Settleman Jeffrey , Ramaswamy Sridhar 
Published: February 2011

Abstract
A fundamental challenge in cancer genomics is to efficiently identify biologically relevant candidate oncogenes from the large amount of molecular information generated in human cancer studies from various high throughput modalities. METHODS. We developed the DELTA (Difference in Expression Lined to Amplification) measurement to systematically identify candidate oncogenes in human cancer cell lines. We applied this metric to a large, diverse collection of 365 cancer cell lines densely profiled at both the expression and genomic level using the Affymetrix U133X3P and 500K Mapping arrays. RESULTS. We first identified recurrent cancer-driving amplification events using a GISTIC-inspired approach. This algorithmic analysis revealed 170 amplicons across 18 different cancer types. The majority of these recurrent amplicons do not contain known oncogenes. We then used the DELTA metric to further prioritize candidate oncogenes within these recurrent amplicons. Systematic shRNA knock down of these candidates was then used to identify SOX2 and S100A8 as candidate oncogenes in esophageal and lung cancer cell lines, respectively. CONCLUSION. Differential gene expression analysis with the DELTA metric may be useful for the functional analysis of recurrent genomic amplicons across human cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2203.
Abstract 2208: High-resolution analysis of insertional mutagenesis screens to study genetic interactions in heterogeneous tumors
Authors: Koudijs Marco J. , Kool Jaap , Sie Daoud , Prasetyanti Pramudita , Cuppen Edwin , Berns Anton , Hilkens John , van Lohuizen Maarten , Adams David , Jonkers Jos 
Published: February 2011

Abstract
Insertional mutagenesis (IM) screens in genetically engineered mouse models of cancer are a powerful tool to identify genes or regions in the genome contributing to tumorigenesis. Current methods to identify the integration sites are not quantitative and do not give information about the clonality of a given insertion in a tumor. Consequently, the results of IM screens are hard to interpret since the obtained data are incomplete and highly biased due to technical variation.
We have developed and optimized a next-generation sequencing-based method for ultra high-throughput analysis of insertional mutations in a less biased and quantitative manner. Integration sites of retroviral or transposon based insertional mutagens are amplified using Splinkerette-mediated PCR and subsequent 454 sequencing. In contrast to current protocols, based on restriction enzyme (RE) fragmentation, we randomly shear gDNA, which allows a random ligation of the Splinkerette. This enables us to generate randomly sized amplicons per integration, which reduces amplification- and sequencing bias compared to amplicons with a fixed length per integration using RE based methods. Since Splinkerette ligation can occur at every base pair, we can determine the amount of cells containing the given insertion by counting unique ligation points, each representing a unique chromosome, and thereby a cell, in the tumor. This latter feature, addressing clonality of an insertional mutagen, will allow the identification of both clonal and sub-clonal mutations in genetically heterogeneous tumors. More importantly, we are now able to study co-occurring mutations, e.g. underlying synthetic lethality, which cannot be performed reliably using the current method.
The insertional mutagenesis data obtained with the improved method will represent the biological situation of a given integration within a tumor, thereby facilitating subsequent validation experiments. Additionally, data obtained from our retroviral- and transposon-based screens in various mouse models of cancer will serve as a catalogue of cancer-relevant mutations that can be used for cross-species comparative analysis of the large numbers of mutations found in human breast cancer.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2208.
Abstract 2217: Analysis of mitochondrial variations in non-small cell lung cancer (NSCLC) by microarray-based genome resequencing
Authors: Wang Zhaoxi , Choi Sojung , Huang Yen-Tsung , Chen Feng , Lin Xihong , Neuberg Donna , Kim Jhin , Christiani David C. 
Published: February 2011

Abstract
The human mitochondrial genome is a circular double-stranded DNA molecule (mtDNA) of 16,569 base pairs, encoding 13 proteins that are essential in oxidative phosphorylation, two ribosomal genes, and 22 tRNAs. The mtDNA genome has a high copy number per cell, replicates independently of the nuclear genome, and has a maternal-inherited pattern. Mutations in mtDNA genome have long been suspected to play an important role in the development of cancer. Although most cancer cells harbor mtDNA mutations, the question of whether such mutations are associated with clinical prognosis of cancer remains unclear. In this study, we resequenced the entire mitochondrial genomes of tumor tissue from a population of 249 Korean non-small cell lung cancer (NSCLC) patients using the Affymetrix GeneChips Human Mitochondrial Resequencing Array 2.0 (Santa Clara, CA). A total of 892 single nucleotide polymorphisms (SNPs) were identified, including 269 (30.2%) synonymous SNPs, 142 (15.9%) non-synonymous SNPs, 78 (8.7%) SNPs in non-coding region, 188 SNPs (21.1%) in control region, as well as 215 (24.1%) previously unreported SNPs. Each tumor sample contained at least 6 mitochondrial SNPs, with maximum 41 SNPs. We selected 189 (21.2%) SNPs with frequency &gt;2.5% for subsequent analyses. Single SNP analysis using Cox proportional hazards models identified 19 SNPs with p value &lt; 0.05, but none of them remained significant after adjustment for multiple comparisons. Unsupervised clustering analysis revealed two major SNP signature panels, including Signature Panel 1 (8 SNPs) and Signature Panel 2 (5 SNPs). Accordingly, the patient population was divided into three groups: 68 (27.3%) subjects with both signature panels, 73 (29.3%) subjects with only the Signature Panel 1 but not the Signature Panel 2, and 108 (43.4%) subjects without signature panel. In early stage (stage I/ II) NSCLC, patients with the Signature Panel 2 had the worst clinical prognosis, and patients without any signature panel performed best in the survival analyses (adjust hazard ratio=1.83; 95% confidence interval, 1.25-2.66; p=0.003). Further mitochondrial haplogroup analysis identified that the Signature Panel 1 had most defining mutations for haplogroup M and N, and the Signature Panel 2 contained all defining mutations of haplogroup D4a. Interestingly, haplogroup D4a was previous reported as a marker for extreme longevity in Japanese. We conclude that mtDNA mutations may play an important role in survival among early stage lung cancer patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2217.
Abstract 2220: Analyzing cancer with single cell resolution using droplet technology
Authors: Samuels Michael L. , Kennedy Scott 
Published: February 2011

Abstract
Cancers develop and grow in the complex environments present in normal tissue, and tumor cells are composed of heterogeneous mixtures of both clonal transformed cells and other cell types. We demonstrate the use of microfluidic-generated single cell microdroplets in workflows that capture both phenotypic and genomic information from individual cells, enabling analysis of tumors with single cell resolution. This transformative new tool will allow for more thorough examinations of the variations that influence the predisposition and composition of cancers, and the cellular responses to therapeutic and prevention agents. Uniform picoliter-nanoliter volume aqueous droplets suspended in an immiscible oil provide unique opportunities for fluorescence-based analytical techniques, including sorting relevant sub-populations at rates of several hundred cells per second, coupled directly to single cell genomic characterization. We use a defined set of control samples to perform low-bias single cell whole genome amplification (WGA) within the sorted microdroplets, and show how following this with droplet PCR-based targeted amplification (of many thousands of selected genomic loci using a cancer-focused droplet primer library) provides an automated sample preparation method for any Next Gen sequencing platform. Single cell microdroplet technology results in a cost-effective method to gain sequence information from phenotypically selected individual cells, addressing cancer gene discovery and validation by powering the larger studies required to classify driver or passenger mutations and analyzing how epigenomic features (such as cytosine methylation) regulate transcriptional changes that can underlie cancer development.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2220.
Abstract 2224: Next-generation sequencing and bioinformatics analysis identified up-regulation of TGFBI and SOX4 in human glioblastoma
Authors: Lin Biaoyang , Madan Anup , Fang Xuefeng , Yoon Jae-Geun , Foltz Gregory 
Published: February 2011

Abstract
A comprehensive network-based understanding of molecular pathways abnormally altered in glioblastoma multiforme (GBM) is essential for developing effective therapeutic approaches for this deadly disease. Applying a next generation sequencing technology, massively parallel signature sequencing (MPSS), we identified a total of 4535 genes that are differentially expressed between normal brain and GBM tissue. The expression changes of three up-regulated genes, CHI3L1, CHI3L2, and FOXM1, and two down-regulated genes, neurogranin and L1CAM, were confirmed by quantitative PCR. Of note, pathway analysis revealed that TGF- β was significantly up-regulated in GBM tumor samples. An integrative pathway analysis of the TGF β signaling network identified two novel TGF—β signaling pathways mediated by SOX4 (sex determining region Y-box 4) and TGFBI (transforming growth factor beta 1 induced). Quantitative RT-PCR and immunohistochemistry staining showed that their expressions are elevated in GBM tissues compared with normal brain tissues at RNA and protein levels. In vitro functional studies confirmed that TGFBI and SOX4 expression is increased by TGF- β stimulation and decreased by a specific inhibitor of TGF- β receptor 1 kinase. The comprehensive identification of genes involved in TGF- β signaling provides further insight into GBM biology and novel therapeutic targets for further investigation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2224.
Abstract 2234: Circulating tumor cells are rare in patients with curable oligometastatic cancer
Authors: Boffa Daniel J. , Guo Xiaojie , Molinaro Annette , Finan Betsy , Detterbeck Frank , Rimm David L. 
Published: February 2011

Abstract
Background: In the majority of patients with solid organ malignancies, tumor metastasis marks a transition from curable to terminal. However, a subset of metastatic cancer patients develops only a very limited number of metastases (known as oligometastatic). Survival in this cohort is considerably better than patients with widely disseminated cancer. In fact, in highly select subgroups, as many as 30% of oligometastatic patients are actually cured of cancer.
The mechanism that distinguishes limited (or oligometastatic) cancer, from the more lethal, widely disseminated, is unknown. Tumor cell circulation is a critical component of metastasis formation, with circulating tumor cells being detectable in as many as 40-70% of patients with metastatic cancer. We hypothesize that patients with limited metastasis formation, have limited tumor cell circulation. To test this hypothesis, we quantified circulating tumor cells in patients with oligometastatic disease.
Methods: Circulating tumor cells (CTCs) were quantified in patients with metastatic epithelial malignancies using the Veridex assay. Patients with &gt; 2 CTCs in a 7.5 ml specimen were considered positive, as a single CTC has previously been shown to carry a substantially higher false positive rate (6.4%) than &gt;2 CTCs (.3%).
Results: From April 2008 to December 2009, a total of 20 patients with oligometastatic cancer were enrolled. In all patients the primary tumor had been previously removed and each was being evaluated for curative surgery to remove the oligometastatic cancer. The origin of the primary tumor was colon (17 patients), head and neck (1 patient), ovarian (1 patient), and pancreas (1 patient). The site of oligometastatic cancer was the liver (12 patients), lungs (4 patients) or both liver and lungs (4 patients). Only 1 of the 20 patients with oligometastatic cancer (5%) was found to have &gt;2 circulating tumor cells. During the same time frame, CTCs were more common in patients with disseminated cancer as 4 of 7 patients (57%) with incurable, widely disseminated metastatic cancer had &gt; 2 CTCs (two tailed P value = .0089).
Conclusions: Circulating tumor cells are rare in patients with oligometastatic cancer.
One mechanism by which oligometastatic cancer patients avoid more widely disseminated cancer may relate to the frequency and duration of tumor cell circulation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2234.
Abstract 2246: Identification of genomic alterations associated with metastasis and poor prognosis in clear cell renal cell carcinoma
Authors: Sanjmyatav Jimsgene , Schwaenen Carsten , Wessendorf Sven , Kreuz Marcus , Steiner Thomas , Wunderlich Heiko , Fuessel Susanne , Junker Kerstin 
Published: February 2011

Abstract
Introduction: Clear cell renal cell carcinoma (ccRCC) is the most frequently encountered renal malignancy with a high metastatic potential and the prognosis of patients in this subgroup is very poor. Prognostic parameters which can be used for an individual prognostic evaluation are still not available, So the aim of our study was high resolution screening of genomic imbalances of metastasized and non-metastasized primary ccRCC by array CGH in order to identify regions of DNA copy number changes significantly associated with metastasis and clinical outcome of patients.
Methods: We conducted genome-wide copy number profiles in 56 primary ccRCC including 32 metastasized and 24 non-metastasized tumours by array CGH with a median resolution of 2Mbp. The median follow up of the patients was 47 months.
Results: Array CGH identified 6 recurrent chromosomal aberrations: gains of 1q21.3, 12q13.11, 12q13.2 and 20q11.21q13.2 and losses of 8p11.23p12 and 9p21.3p24.1, which were significantly associated with metastasis occurrence. In multivariate analysis including these aberrations gains of 1q21.3 and of 20q11.21q13.2 and loss of 9p21.3p24.1 attained as independent predictors for metastasis in our cohort with 81.5% sensitivity and 95.8% specificity of 81.5% and 95.8%, respectively. Kaplan-Meier survival analysis showed that gains on chromosomes 7, 12, 16 and 20q and losses on chromosome 9 have a significant correlation with disease specific survival. Multivariate Cox-regression analysis revealed gains of 7q36.3 and of 20q11.21q13.2 and a loss of 9p21.3p24.1 as independent prognostic factors for patients' outcome of patients.
Conclusions: Our data suggest that specific common copy number alterations in ccRCC could serve as independent predictors for metastasis occurrence and cancer specific survival in patients with ccRCC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2246.
Abstract 225: Cytotoxic extracts of ethnomedicinal plants Podophyllum peltatum (Mayapple) and Echinacea angustifolia
Authors: McDowell Olena T. , Myles Elbert L. 
Published: February 2011

Abstract
Phytochemicals and other natural compounds are historically established as cures for many ailments in rural America and developing countries. Our lab is testing plants that show potential for inhibiting the growth of cancer cells. The family Asteraceae and the family Berberidacae are very well known for there values as medicinal plants. More specifically, the genus species Echinacea angustifolia and genus species Podophyllum peltatum commonly known as the Mayapple, both are noted for there unique medicinal purposes. The crude methanolic extracts of these plants were tested against human metastatic cell lines representing breast (MCF-7),(BT-549), and (BT-20) tissues. Trypan blue exclusion is used to determine viable cell counts. Alamar BlueTM and florescent analysis were used to evaluate the cytoxicity of the extracts. Analysis of the crude extracts of Echinacea angustifolia has shown on MCF-7, BT-549 and BT-20 that most of them exhibit anticancer activity against the cell lines at the maximum concentration of 200 g /mL. In particular, less diluted concentrations have demonstrated exceptional inhibitory effects with IC50 values ranging between 0.10-15 g /mL, respectively. On the other hand, analysis of the crude extracts of Podophyllum peltatum (Mayapple) has shown on MCF-7, and BT-549 some anticancer activity against cell lines at the maximum concentration of 200 g /mL. More specifically, the more diluted concentrations have demonstrated exceptional growth inhibition with IC50 values ranging between 2-8g /mL
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 225.
Abstract 2258: Targeting MACC1: In vivo imaging of distant metastases reduction by MACC1-shRNA in human colon cancer xenografts
Authors: Stein Ulrike S. , Sack Ulrike , Kobelt Dennis , Kelch Inken , Fichtner Iduna , Walther Wolfgang , Schlag Peter M. 
Published: February 2011

Abstract
We identified the previously undescribed gene MACC1 by a genome-wide search for differentially expressed genes in human colon cancer tissues, metastases and normal tissues. MACC1 plays an important role for metastasis prediction, in particular for early-stage patients. Based on MACC1 mRNA expression in not (yet) metastasized primary colon cancers of stages I, II and III, our negative and positive prediction of the development of metachronous distant metastases was correct to 80% and 74%, respectively. The 5-year-survival for subjects suffering from colon cancer was 80% for MACC1 low expressors, but 15% for individuals with high MACC1 expression in their primary tumors. Moreover, we found MACC1 to act as an inducer of migration, invasion and proliferation in cell culture, and of distant metastases in several xenograft models. MACC1 transcriptionally regulates the receptor tyrosine kinase Met, that activates the HGF/Met signaling pathway resulting in enhanced cell motility, invasion and metastasis. Here we report the reduction of metastasis by using shRNA targeting the metastasis-inducer MACC1 in vivo. MACC1 high expressing human colon cancer cells were transfected with MACC1-shRNA, Met-shRNA, or control-shRNA harboring plasmids, together with luciferase-containing constructs. Cell clones were intrasplenically transplanted into mice. Tumor growth and metastases formation was demonstrated by in vivo imaging. Signals in MACC1-shRNA/luc mice and in Met-shRNA/luc mice originated exclusively from spleen tumors, not from liver metastases, as demonstrated with the isolated organs by luminescence. By contrast, signals in control-shRNA/luc mice originated from spleen tumors and liver metastases. These findings were confirmed by brightfield images, demonstrating reduced tumor growth and metastases development in MACC1-shRNA/luc and Met-shRNA/luc mice compared to control-shRNA/luc mice. In summary, knock down of MACC1 by MACC1-shRNA led to reduction of tumor growth and metastasis in mice, making MACC1-shRNA a useful tool for metastasis intervention of colon cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2258.