bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5066: Genome sequence and epigenome map of bladder cancer development from occult field effects
Authors: Czerniak Bogdan A. , Majewski Tadeusz , Bondaruk Jolanta , Zhang Shizhen , Lee Sangkyou , Baggerly Keith , Dinney Colin , Grossman H. Barton , Wu Xifeng , Issa Jean-Pierre , Zhang Wei , Gibbs Richard , Scherer Steven E. 
Published: August 2012

Abstract
We are pursuing a unique strategy to identify early events in bladder cancer development by the genome-wide analysis of somatic changes in tissues from resected bladders and characterized pathologically as urothelial carcinoma. We then extend this analysis into precursor intraurothelial lesions and normal tissue. Here we report on the construction of a high resolution whole-organ histologic and genetic map of bladder cancer development that tracks its progression from in situ precursor conditions to invasive clinically aggressive cancer using total genome and exome sequencing and complemented with HumanOmni 2.5-8 v1 SNP-based Illumina genotyping, combined with CpG island methylation and cDNA microarray platforms derived from 12 whole-organ cystectomy specimens with invasive urothelial carcinoma. This approach provided a high resolution integrated map of structural genome, epigenome, and transcriptome alterations that parallel the development of bladder cancer from early field effects to invasive disease. By analyzing genome-wide patterns of structural genomic, epigenomic, and transcriptome changes, we found three major waves of alterations associated with growth advantage of successive clones reflecting a stepwise conversion of normal urothelial cells into cancer cells. This approach is significant for the identification of specific chromosomal regions as well as epigenetically and transcriptionally modified gene ontologies involved in early clonal expansion of intraurothelial neoplasia and their clonal evolution to carcinoma in situ progressing to invasive cancer. These studies suggest involvement of specific gene networks in early clonal expansion of intraurothelial neoplasia antecedent to microscopically recognizable precursor lesions such as dysplasia and carcinoma in situ. This map represents a prerequisite for specific studies on the mechanisms of incipient phases of bladder cancer development and should have a significant impact on the understanding of human carcinogenesis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5066. doi:1538-7445.AM2012-5066
Abstract 5070: Paired-end RNA-sequencing reveals novel fusion genes and SNVs in osteosarcoma
Authors: Moon So Young , Bilke Sven , Davis Sean , Walker Robert L. , Pineda Marbin , Zhu Yuelin Jack , Abaan Ogan , Meltzer Paul S. 
Published: August 2012

Abstract
Osteosarcoma is an aggressive cancer of bone, which typically occurs during adolescence. The genetic hallmark of osteosarcoma is the presence of extensive and complex genomic rearrangements. However, few consistent aberrations have been identified, hampering the development of targeted therapy for osteosarcoma. Next generation RNA-sequencing (RNA-seq) is a powerful tool for comprehensive characterization of whole transcriptome, with the unique ability of identifying novel fusion genes. We applied paired-end RNA-seq to explore the transcriptome of 16 human OS cell lines and primary osteoblasts from two healthy individuals. On average, about 21.6 million sequencing reads and 10.6 million aligned reads were obtained for each sample. Several thousand SNVs (single nucleotide variants) that have not been reported in the dbSNP database were identified. Bioinformatic analysis identified several fusion genes (e.g. PAFAH1B2-FOXR1and FAM119B-TSFM), which involved both known cancer related genes as well as genes previously unrelated to cancer. Fusion transcripts were validated using RT-PCR, Western blot and capillary sequencing. These rearrangements tended to occur at copy number transitions on the partner chromosome regions. Our findings have the potential to provide important insights into osteosarcoma biology, and potential translational applications for diagnostic and therapeutic development.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5070. doi:1538-7445.AM2012-5070
Abstract 5072: Genome sequencing of metastatic colorectal carcinomas to identify potential targets for therapy in patients
Authors: Shanmugam Viji , Ramanathan Ramesh K. , Sinari Shripad , Chadha Manpreet , Liang Winnie , Kurdoglu Ahmet , Izatt Tyler , Christoforides Alexis , Benson Hollie , Phillips Lori , Baker Angela , Hostetter Galen , Von Hoff Daniel D. , Craig David , Carpten John 
Published: August 2012

Abstract
Colorectal carcinoma is one of the most common cancers in the western world, being the third most common cause of cancer-related morbidity and mortality. The outcome of patients with metastatic colorectal carcinoma (mCRC) following first line therapy, especially with a Kras mutation is poor with median survival of less than one year. The purpose of this study was to identify therapeutically actionable somatic events in mCRC patient samples, so as to obtain select targeted treatment strategies for individual patients. Fresh frozen needle biopsies of liver metastases were collected from three mCRC patients along with whole blood for the extraction of constitutional DNA. All patients had greater than 2 prior regimens and had known K-ras mutations. Whole genome sequencing was performed using Illumina paired-end chemistry on HiSeq2000 sequencing system, which yielded coverage of greater than 30X for both the normal and tumor samples. Somatic genomic alterations (point mutations and indels, copy number alterations, translocations and rearrangements) were analyzed using our custom pipeline for paired analysis. We found that all 3 tumor samples had KRAS mutations, while 2 samples had mutations in the APC gene and the PIK3CA gene. Other genes with therapeutic implications in single tumor samples were INPPL1, INPP4B and SMAD4. No EGFR amplifications were detected in our sample set. Pathway analysis revealed K-RAS regulation and apoptosis and survival pathways in these tumor samples. Analysis of paired-end data from these three tumors did not reveal the presence of translocations at the recently discovered TCF7L2 locus (Bass et al, Nature Genetics, 2011). The concomitant mutations in MAPK (KRAS) and PI3K (PIK3CA, INPPL1, INPP4B) pathways suggest that combination therapies might be required for effective treatment of these tumors. By harnessing the power of Next-Gen Sequencing, our study has revealed a series of therapeutically actionable events in mCRC that might provide insights into treating these difficult to treat advanced tumors.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5072. doi:1538-7445.AM2012-5072
Abstract 5077: Array CGH genomic profile of hereditary breast cancer tumors: Identification of tumor suppressor genes in deleted regions, determination of promoter hypermethylation and their protein expression in tumor biopsies
Authors: Alvarez Carolina , Tapia Teresa , Cornejo Valeria , Aravena Andres , Fernandez Wanda , Alvarez Manuel , Camus Mauricio , Maass Alejandro , Carvallo Pilar 
Published: August 2012

Abstract
Breast cancer, as other cancer types, is a genetic disease caused by sequential accumulation of mutations and genomic alterations involving tumor suppressor genes and oncogenes. In this matter, inactivation of tumor suppressor genes may occur by deletion, promoter hypermethylation or point mutations. We analyzed by array-CGH tumor DNA from 52 patients with hereditary breast cancer: 3 BRCA1, 4 BRCA2 and 45 from patients with no identified mutations (BRCAX). Our analysis revealed that BRCA1 mutated tumors have different genomic alterations compared to BRCA2 tumors. BRCAX tumors showed frequent deletions at: 1q21.3 (20%), 1p31.1 and 9q33.1 (18%); and frequent amplifications at 1q23.1 (20%), followed by 1q21.1 and several gains in chromosome 19 (18%). All genes involved in the deleted or amplified regions were compared with gene expression data in the ONCOMINE database finding correspondence among genomic alterations and gene expression. Based on these results, we selected 3 tumor suppressor genes for promoter methylation and protein expression analyses: RASSF1A, SLIT2 and WIF1. Methylation analysis through MS-PCR revealed that RASSF1A promoter was hypermethylated in 67% of hereditary tumors, and significantly associated to loss of expression (p=0.007, OR 9.6, CI 1.77-52.19). WIF1 promoter was hypermethylated in 68% of tumors with a significant association to loss of expression (p=0.042, OR 6.4, CI 1.155-35.45). Finally, SLIT2 was found as the most frequently hypermethylated promoter among tumors (80%) showing loss of expression in 90% of these tumors. Our results indicate that silencing of RASSF1A, SLIT2 and WIF1 through promoter hypermethylation may have an important role in hereditary breast tumor development. Fondecyt 1040779 y 1080595.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5077. doi:1538-7445.AM2012-5077
Abstract 5098: Identification of copy number alterations associated with the progression and clinical outcomes of oral cavity squamous cell carcinoma
Authors: Chien Huei-Tzu , Huang Shiang-Fu , Cheng Sou-De , Chen I-How , Liao Chun-Ta , Wang Hung-Ming , Hsieh Ling-Ling 
Published: August 2012

Abstract
The molecular mechanisms contributing to the progression of oral cavity squamous cell carcinoma (OSCC) remain poorly understood. The primary treatment for advanced-stage OSCC is radical surgery with post-operative chemoradiation. However, the prognoses are usually discouraging. If we can better understand the characteristics of OSCCs, this may ultimately help clinicians to provide OSCC patients with more appropriate treatment. The advent of genome-wide profiling methods has opened up new possibility to catalogue chromosomal abnormal regions at high resolution. In the present study, 72 advanced-stage OSCCs were analyzed using two microarray platforms (26 cases with Affymetrix SNP 500K and 46 cases with Affymetrix SNP 6.0). Genomic copy number was determined by calculating the intensity ratio between the OSCC and a set of 270 normal DNAs from HapMap project. Segmented copy numbers for each tumor were inferred with the hidden markov model (HMM) using the Partek GS software. To identify regions for copy-number alterations (CNAs), GISTIC (genomic identification of significant targets in cancer) was applied to determine the significance. With this approach, 46 (14 gain and 32 loss) and 208 (48 gain and 160 loss) significant regions (FDR q-value &lt; 0.25) were identified from SNP 500K and SNP 6.0 platform, respectively. Among them, 15 focal CNAs (8 gains (3q26.1, 7p11.2, 11q13.3, 13q22.1, 15q11.2, 17p13.3, 18p11.23-18p11.31, and 20p11.22) and 7 losses (1q21.1, 6p21.33, 7q31.3, 12q14.1, 2 focal regions in 14q11.2, 15q11.2)) are identical in these 2 platforms. Amplification of 11q13.3 containing a known oncogene CCND1 was confirmed by fluorescence in situ hybridization (FISH) with Vysis CCND1/CEP11 FISH probe kit. The clinicopathologic significances of these 15 CNAs were examined. Gain of 3q26.1 and 18p11.23-18p11.31, and loss of 15q11.2 were correlated significantly with lymph node metastasis. Furthermore, loss of two focal regions in 14q11.2 was significantly associated with disease-free and overall survival. In conclusion, CNAs associated with the progression and clinical outcomes of Taiwanese OSCC were identified by genomic approach using high-density SNP array. These results provide useful clues for future characterization of important oncogenes or tumor suppressor genes associated with the behaviors of the disease.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5098. doi:1538-7445.AM2012-5098
Abstract 5108: A combined processing and assessment workflow for SNV and indel calling on exome sequencing of tumor samples
Authors: Wong Swee Seong , Calley John N. , Wang Jian , Ting Jason C. , Wulur Isabella H. , Li Shuyu Dan , Yue Yong Gang , Barber Thomas D. , Aggarwal Amit , Donoho Gregory P. 
Published: August 2012

Abstract
A workflow for exome sequencing is established using multiple callers for SNV and indel. A spectrum of measures is looked at to understand the diversity and characteristics of the samples. Two common workflows for variant calling are used, namely GATK unified genotyper and Samtools mpileup. Illumina paired end 90 base reads are mapped to the human genome using BWA. Variants called by GATK and Samtools are compared and merged to give a unified set of calling in VCF format. This approach gives additional confidence in calls supported by both callers as there are technical differences in the two workflows. dbSNP rate and TI/TV ratio are used to assess the general quality (sensitivity and specificity) of the calls. It is observed that tumor samples with very low and high TI/TV novel ratio are largely lung and melanoma samples respectively. They are likely to be UV and smoking induced DNA mutation. This affects the overall TI/TV ratio. A handful of samples also exhibit high variant count that is uniquely found (private) in the sample alone. This correlates with lower than expected dbSNP rate.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5108. doi:1538-7445.AM2012-5108
Abstract 511: Characterization of humoral response profiles of ovarian cancer patients as diagnostic biomarkers
Authors: Roberson Carolyn D. , Gercel-Taylor Cicek , Taylor Douglas D. 
Published: August 2012

Abstract
Ovarian cancer is the 5th leading cause of cancer death among women and is the leading cause of death among gynecologic malignancies as a result of limitations in early diagnosis. It is associated with the induction of humoral immunity, characterized by the generation of IgG against a wide range of tumor-associated antigens. Although the role of circulating tumor-reactive IgG is unclear, it has been demonstrated to correlate with poor prognosis and survival. The use of tumor-reactive IgG as a potential diagnostic and/or prognostic tool has been limited since most studies have identified components with shared expression in non-neoplastic tissue and failed to define targets exhibiting ubiquitous expression in ovarian cancers. A number of these limitations result from the use of recombinant proteins (translated in non-mammalian cells) as targets to define immunoreactivity. The power in utilizing the autologous humoral response is its ability to define alterations which might lead to the altered appearance or aberrant association of antigen with other cellular components, thereby resulting in the induction of humoral responses. We therefore hypothesize that the ovarian patient humoral response to specific tumor antigens can serve as diagnostic biomarkers of ovarian cancer. To investigate patients’ humoral response to “natural” tumor antigens, ovarian tumor cell lysates and tumor-derived exosomes were separated into antigenic proteins by first dimension isoelectric focusing via an immobilized pH gradient and/or rotofor fractionation. Reactive proteins were further separated by second dimension SDS-PAGE, followed by western immunoblotting using autologous or heterologous patient sera. Circulating tumor-reactive IgG was found to recognize shared (MW 37-75 kD, pI 3.0-5.5) and distinct (MWexo ∼50 kD, pI 9.0-10.5; MWlys∼15 kD, pI 4.3-6.5) ovarian tumor cell proteins. Recognition of these antigenic proteins was not observed using antibodies derived from normal control patients. Collectively, our data supports that the circulating IgG produced in the ovarian cancer humoral response recognizes specific tumor antigens (many of which are shared among cancer patients) and will thus have utility in diagnosing these patients. Further identification of these antigenic proteins by mass spectrometry will produce specific diagnostic targets and may provide insights on common driver mechanisms in ovarian cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 511. doi:1538-7445.AM2012-511
Abstract 5110: Divergent gene expression profiles in HPV-positive and HPV-negative head and neck squamous cell carcinomas
Authors: Tomar Swati , Kowli Sangeeta , Altomare Diego , Sutkowski Natalie , Gillespie Marion Boyd , Glover Saundra H. , Creek Kim E. , Pirisi-Creek Lucia A. 
Published: August 2012

Abstract
Up to 60% of oropharyngeal cancers and 25% of head and neck squamous cell carcinomas (HNSCC) are due to high-risk Human Papillomavirus (HPV), primarily HPV16. Differences in risk factors, age of presentation and clinical behavior of these tumors indicate that HPV+ and HPV- tumors develop with different molecular mechanisms and are biologically distinct. To further investigate the molecular characteristics of these tumors, we compared the gene expression profiles of three HPV- and four HPV+ HNSCC specimens, obtained from the Medical University of South Carolina ENT/Head and Neck Surgery clinic. All HPV+ tumors were positive for HPV16 and expressed E7, as documented by real-time RT/PCR using tumor-derived RNA. Gene expression profiles were determined on Agilent 4x44K human oligonucleotide microarrays. Identification of differentially expressed genes (&gt;2-fold change, p&lt;0.05) and pathway analysis were performed using GeneSifter Software (Geospiza). Overall, 125 genes were up-regulated and 223 were down-regulated in HPV+ in comparison with HPV- tumors. Gene Ontology analysis of the dataset revealed that pathways related to cell cycle control, mitotic checkpoint, regulation of cell proliferation, programmed cell death and DNA metabolism were heavily affected in HPV+ tumors, while pathways affected in HPV- tumors included regulation of cell motility and migration, angiogenesis and integrin-mediated signaling. We confirmed by Real-Time RT/PCR the differential expression of a panel of genes of interest on these samples and several additional HNSCC specimens, and then we extended our follow-up analysis to specimens from over 30 new cases of HNSCC. Among the genes we targeted for follow-up is the MET oncogene, which encodes the hepatocyte growth factor/scatter factor receptor. MET is overexpressed about 5-fold in HPV- tumors, in comparison with HPV+ tumors actively expressing E7. The MET product, which controls growth, invasion and metastasis in cancer cells, has been recently proposed as a new therapeutic target for HNSCC. Supported by grant #P20MD001770 from the NIH/NIMHD.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5110. doi:1538-7445.AM2012-5110
Abstract 5121: Acquired inactivating ARID2 mutations in lung non small cell carcinoma
Authors: Didelot Audrey , Letouzé Eric , Manceau Gilles , pallier Karine , Guichard Cecile , Cazes Aurélie , Fabre Elizabeth , Zucman-rossi Jessica , Laurent-Puig Pierre , blons Helene F. 
Published: August 2012

Abstract
The genetic alterations involved in the development lung adenocarcinoma (ADC) have been widely characterized allowing the identification of the most frequent oncogenes or tumor suppressor genes linked to this malignancy. Most studies have focus on proliferation pathway, anti-apoptotic factors or cell cycle alterations. Here we show that alterations in chromatin remodeling complexes are frequent in lung ADC. Chromatin structure plays a key role in the regulation of tissue-specific gene expression during development and differentiation therefore it is not surprising that proteins implicated in remodeling complexes play a role in cancer development. For example, mutations have been found in genes belonging to the SWI/SNF complex in different tumors. In lung cancer BRG1 knockout was shown to potentiate tumor development and mutations were recently identified in tumors by the use of a very sensitive method: massive parallel DNA pyrosequencing that suggests the presence of the alteration in cell subclones. In the course of identifying novel chromatin remodeling complex genes implicated in lung ADC development we analyzed a series of 82 lung adenocarcinomas by SNP array and looked for the presence of homozygous deletions on the entire genome. Three regions of homozygous deletions in known tumor suppressor genes CDKN2A, FHIT and PTEN and in JARID2, which is involved in chromatin remodeling, were found in more than 2 samples. Another ARID-domain containing gene; ARID2 was found deleted in one sample and we therefore decided to screen both ARID-domain genes for mutations by direct sequencing on cryopreserved tumor tissues. One missense somatic mutation was found in JARID2 and 6/82 tumors had ARID2 alterations predicted to inactivate the protein in at least 4 out of 6 samples. Indeed 3 mutations were frameshift or non-sense, one specimen had a homozygous deletion and 4 tumors demonstrated loss of heterozygosity associated to the mutation. Our results indicate that ARID2 inactivation is a common feature of lung cancer development and provide new insight on the impact of chromatin remodeling alteration in lung ADC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5121. doi:1538-7445.AM2012-5121