bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2128: Whole transcriptome sequencing in normal and cancer prostate tissue
Authors: Tang Wei , Prokunina-Olsson Ludmila 
Published: February 2011

Abstract
Prostate cancer (PrCa) is the second most common type of cancer in males. Established risk factors for PrCa are age, ethnicity and family history. PrCa shows consistent evidence of familial aggregation and heritable factors have been estimated to explain 42% (29-50%) of disease risk in individuals of European ancestry. More than 20 regions harboring genetic risk variants associated with increased risk of PrCa have been identified through Genome-wide association studies (GWAS) to date (MSMB, HNF1B, SLC22A3, LMTK2, KLK2-KLK3, NUDT11, THADA, ITGA6, PDLIM5, TET2, NKX3.1, TH, TTLL1, EHBP1, CTBP2, JAZF1 and 3p12.1, 7p15.3, 8q24, 11q13.3 and 12q13.13 genomic regions). We began to investigate and characterize the entire transcriptome of normal and cancer prostate tissue through a massively parallel sequencing technology (Illumina /Solexa Genome Analyze II). We generated transcriptome profiles based on 36 or 72 bp paired-end reads for cell lines established from cancer and matching normal tissue from two patients. To analyze the data, we used BWA, Bowtie, Tophat packages and Partek Genomics Suite software.
More than 80% of the sequence reads were mapped to the human reference sequence (hg19). The aligned sequences were examined for presence of alternative splicing forms, novel exons, non-coding transcripts and chimeric events compared with a reference transcript annotation from RefSeq Genes of UCSC genome browser database. Based on RPKM algorithm, we also evaluated the expression level in the cancer and normal tissues. We detected over 70,000 transcripts and of ∼ 5, 000 of them were novel splicing isoforms not present in the UCSC database. We examined transcriptome landscape in GWAS-identified loci associated with PrCa. Within the 8q24 region we observed differential expression or evidence of alternative transcripts for SRRM1L, POU5F1B and LOC72767. Within 11q13.3 we observed a novel transcript found only in normal prostate tissue. Many of the risk candidate genes such as ITGA6, PDLIM5, THADA, TET2, SLC22A3, CTBP2 and EHBP1 had multiple splicing isoforms and some of these isoforms were differentially expressed between normal and tumor samples. The expression of alternative transcripts will be confirmed by qPCR in independent samples and correlated with cancer -associated genetic variants identified by GWAS. In conclusion, we generated a resource for studies of PrCa. This reference set will be useful for functional exploration of genetic association signals detected through GWAS.
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 2128.
Abstract 2129: Pediatric diffuse intrinsic pontine gliomas are genetically distinct from high and low grade astrocytomas
Authors: Pawel Buczkowicz , Bartels Ute , Morrison Andrew , Zarghooni Maryam , Bouffet Eric , Hawkins Cynthia 
Published: February 2011

Abstract
Tumors of the central nervous system constitute the most common type of solid pediatric tumors and account for the majority of mortality and morbidity in pediatric oncology. Brainstem glioma (BSG) is a type of brain tumor that arises in the medulla, pons or midbrain and accounts for approximately 10-20% of pediatric brain tumors. Diffuse gliomas of the pontine region, diffuse intrinsic pontine glioma (DIPG) are the most common type of brainstem tumor, accounting for about 58-78% of BSG and the number one cause of brain tumor related death in children with a 1-2 year survival. Despite this very little is understood about the biology of these tumors. To try to address this lack of knowledge we have undertaken genomic analysis of a series of DIPGs and compared their copy number changes to those seen in pediatric supratentorial high grade astrocytomas as well as low grade astrocytomas. Post mortem tumor and matched normal brain samples (n= 9) and surgical samples (n= 4) were collected for a series of DIPG patients. We performed high-resolution genetic analysis using whole-genome single-nucleotide polymorphism (SNP) arrays (Affymetrix 500K and 6.0). Data analysis was conducted using Partek Genome Suite and Copy Number Analysis Tool (Affymetrix). Analysis of copy number alterations returned hits in several cancer related pathways including MAPK, Wnt, prostate cancer and gliomagenesis. DIPG copy number was also compared to that of pediatric high grade (n= 20) and low grade (n= 30) astrocytomas. Unsupervised Pearson's Dissimilarity clustering resulted in 3 distinct groups. One contained 6 DIPGs; the second contained mostly LGA with a few HGA, while the third group contained mostly HGA with the remaining DIPGs clustering with this group. Although there were some similarities, DIPG are genetically distinct from supratentorial high grade and low grade astrocytomas. A better understanding of DIPG biology is needed in order to develop agents targeted more specifically towards this disease particularly given the dismal prognosis and unresponsive nature of these tumors to conventional treatment.
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 2129.
Abstract 2130: Genomic profiling identifies CDX2 as a lineage-dependent oncogene amplified in colorectal cancer
Authors: Salari Keyan , Cuff Justin , Giacomini Craig P. , Lin Albert , van de Rijn Matt , Pollack Jonathan R. 
Published: February 2011

Abstract
Somatic DNA alteration underlies tumor development and progression, and gives rise to tumors with diverse genetic contexts. Characterizing these contexts helps identify driving genetic lesions and potential therapeutic vulnerabilities. Here, we surveyed a collection of 29 colorectal cancer cell lines for DNA copy number alterations and identified in a subset of samples gain/amplification on chromosome 13, which was well represented among the genomic profiles of 344 primary colorectal tumors examined, but not in other tumor types. A minimal region of high-level amplification on 13q12.2, containing the caudal type homeobox transcription factor CDX2, was identified in one cell line and 7 of 123 (6%) primary colorectal tumors. A tissue microarray consisting of an independent set of 83 colorectal tumors confirmed the presence of a subset of tumors harboring copy number gain/amplification of 13q with increased CDX2 protein expression. In the context of genomic amplification, RNA interference experiments showed CDX2 is required for proliferation of colorectal cancer cells and promotes cell cycle progression without an effect on apoptosis. CDX2 is a known transcriptional regulator of normal gut development and intestinal epithelial cell differentiation and maintenance. Here we have shown that for a subset of lineage-derived colorectal tumors, cell proliferation is dependent on the abnormal amplification and overexpression of CDX2. Thus, we nominate CDX2 as a novel lineage-dependent oncogene deregulated in colorectal 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 2130.
Abstract 2134: Copy number variation in low- and high-grade breast tumors
Authors: Ellsworth Rachel E. , Patney Heather L. , Kane Jennifer L. , Hooke Jeffrey A. , Shriver Craig D. 
Published: February 2011

Abstract
Objective Histological grade classifies breast carcinomas into low-, intermediate- and high-grade. Developmental pathways for high-grade disease remain controversial; clinical data have been used to describe both linear models, in which high-grade tumors evolve from low-grade precursors, as well as models that depict low- and high-grade carcinomas as distinct molecular diseases. Genome-wide copy number alterations were examined in low- and high-grade breast tumors to identify genetic changes associated with the etiology of low- and high-grade breast carcinomas.
Methods Tumors were diagnosed and characterized by a single, dedicated breast pathologist. DNA was isolated after laser microdissection from low- (n= 53) and high-grade (n=68) tumors. Genotype data were generated using Human Mapping 250K Sty arrays (Affymetrix). Copy number alterations and LOH were detected using GenomeConsole 3.0.2 (Affymetrix).
Results The most common alterations in low-grade carcinomas were gain of chromosomes 1q (75%) and 16p (58%) and loss of chromosome 16q (86%). These alterations were frequently simple and included the entire chromosomal arm. In contrast, patterns of alterations were complex in high-grade tumors, frequently with alternating gains and losses on a single chromosomal arm. In high-grade tumors, the most frequent alterations included gain of chromosome 1q (85%), 8q (84%), and loss of chromosomes 8p (54%), 14q (57%) and 17p (69%). Loss of 16q (P&lt;0.0000005) and gain of 16p (P&lt;0.005) occurred significantly more frequently in low- compared to high-grade tumors, while gain of 8q24 (P&lt;0.000005) and 10p15-p14 (P&lt;0.00005) and loss of chromosome 17p13 (P&lt;0.00005) occurred significantly more frequently in high- compared to low-grade tumors. Only two samples, one low- and one high-grade, had a “flat” profile with no detectable chromosomal alterations.
Conclusion Low- and high-grade breast tumors are genetically different. Gain of chromosome 1q is common in both low- and high-grade tumors, and may be an early event in tumorigenesis. Given the significantly different patterns of alterations, especially significantly higher loss of chromosome 16q in high- compared to low-grade tumors, high-grade disease may not arise from dedifferentiation of low-grade but rather represent a separate disease defined by unique genetic alterations.
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 2134.
Abstract 2149: Analysis of the cancer-specific correlation between genomic copy number aberration and gene expression in colorectal cancer
Authors: Iwatsuki Masaaki , Mimori Koshi , Baba Hideo , Mori Masaki 
Published: February 2011

Abstract
Background: Recently, the technical innovation in molecular biological fields such as laser micro-dissection (LMD), cDNA microarray and array-based comparative genomic hybridization (array-CGH) have made it possible to analysis both genomic alteration and aberrant gene expression simultaneously at the level of cancer cell obtained from human cancer tissues. The aim of current study is to identify the novel genes to predict disease recurrence or prognosis with the concordant relationship between genomic alterations and aberrant gene expression during the progression of colorectal cancer (CRC).
Materials and Methods: Candidate gene was found using cDNA microarray and array-CGH after LMD in 133 Japanese CRC. We picked up the several genes among the overexpressing genes with genomic amplification on the responsible loci in CRC. The expression of representative gene and its clinicopathlogical significance, including prognosis were evaluated another subset of 98 CRC cases.
Results: We demonstrated that a correlation between chromosomal aberrations and gene expression in CRC was found in 8q, 13q and 20q. We identified 185 genes overexpressig in specific CRC cells among the genes on these chromosomes. We focused on SUGT1 (13q), which is associated with the assembling of kinetochore proteins at the metaphase of the cell cycle. SUGT1 mRNA expression was evaluated in 98 CRC cases to determine the clinicopathological significance of SUGT1 expression. The mean level of SUGT1 mRNA expression in tumor tissue specimens was significantly higher than in non-tumor tissue. The high SUGT1 expression group was characterized by a significantly elevated frequency of recurrence and a significantly poorer prognosis than the low expression group. Furthermore, SUGT1 expression was found to be a significant factor affecting five year overall survival following surgery in multivariate analysis (p = 0.04). Conclusion: We performed cDNA microarray and array-CGH analysis after LMD in a large scale study of Japanese CRC patients to identify new genomically amplified genes and determine the impact of their presence. Our results indicate that identified genes are not influenced by epigenetic alteration or microRNA. Furthermore, from a technical point of view, it is easier to handle genomic DNA than mRNA, as the latter is fragile, and unstable. Therefore, our findings suggest that this method of analysis might uncover additional genes indicative of patient prognosis and sensitivity to anticancer drugs.
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 2149.
Abstract 2156: Integration of whole genome exon array and array CGH analysis in gastric and colorectal cancer cell lines
Authors: Furuta Kazuyuki , Arao Tokuzo , Sakai Kazuko , Nagai Tomoyuki , Tamura Daisuke , Aomatsu Keiichi , Kudo Kanae , Kaneda Hiroyasu , Fujita Yoshihiko , Matsumoto Kazuko , Yamada Yasuhide , Yanagihara Kazuyoshi , Sekijima Masaru , Nishio Kazuto 
Published: February 2011

Abstract
Alternative splicing is a major source of protein diversity and cancer is driven by mutations in genes that control the proliferation of cells. The specific exon abnormality may contribute to the etiology of cancer and may provide selective drug targets. However, most studies of alternative splicing in human disease have used a targeted approach and focused on individual genes among whole genome.
In this study, we evaluated an integrated approach of whole genome scale exon array and SNP array to detect cancer-associated alternative splicing, especially focusing on the protein kinase family. We investigated exon-level expression profiling against 22 gastric and colorectal cancer cell lines using Affymetrix Human Exon 1.0 ST Array. Array-based comparative genomic hybridization (CGH) analysis using high-density SNP Array (Affymetrix 250K Nsp /SNP6.0 Array) was also performed to explore genomic amplification/deletion. Several candidate alternative splicing or abnormalities of specific exon expression were detected in cancer-associated genes which detected genomic amplification/deletion frequently; exampling FGFR2, CDKN2A, and CDH13. We found the gene amplification of FGFR2 with C-terminus truncation. We also detected the existence of short CDH13 transcript resulted from small genomic deletion including consecutive 3 exons. In addition, exon-level expression pattern was compared between gastric and colorectal cancer cell lines. In conclusion, integration of whole genome exon array analysis and array CGH analysis may be a promising approach to explore the alternative exon abnormalities.
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 2156.
Abstract 217: Vitamin E forms induce apoptosis, necrosis, and autophagy and caused accumulation of sphingolipid intermediates in human colon cancer cells
Authors: Rao Xiayu , Jiang Qing 
Published: February 2011

Abstract
Emerging evidence by us and others suggests that certain forms of vitamin E may be promising chemoprevention agents. Here we systemically investigated the effect and mechanism of different forms of vitamin E on the growth and death of human colon cancer HT29 and HCT116 cells. γ-tocopherol (γT), δ-tocopherol (δT), and γ-tocotrienol (γTE) inhibited the proliferation of HT29 and HCT116 cells in a time- and dose-dependent manner, with the potency of γTE &gt; δT &gt; γT. HCT116 cells appeared to be more sensitive to the treatment than HT29 cells. Studies using annexin V and propidium iodide staining revealed that γT (50 µM) and γTE (20 µM) induced externalization of phosphatidylserine and enhanced permeability of the plasma membrane, indicating apoptosis and necrosis. On the other hand, none of the treatments activate caspase-3 and PARP except in HCT116 by γTE at 20 µM. Interestingly, γT, δT and γTE enhanced expression of microtubule-associated protein light chain-3 II (LC3 II) in both HT29 and HCT116 cells, suggesting that these vitamin E forms may induce autophagy. Consistently, electromicroscopic results showed that after 14-h treatment, γTE (20 µM) induced extensive formation of autophagic vacuoles with intact cytoplasmic membrane and little induction of chromatin condensation in HCT116. Myriocin, a specific inhibitor of serine palmitoyltransferase, a key enzyme in de novo synthesis of sphingolipids, partially protected HT29 and HCT116 cells from γTE-induced cell death. Importantly, γTE caused marked accumulation of dihydrosphingosine and dihydroceramide but not ceramide or sphingosine as early as after 8-hour incubation. Because dihydrosphingosine is shown to be a potent inducer of cell death, these findings demonstrated that vitamin E may induce apoptosis, autophagy and necrosis in colon cancer cells by modulation of sphingolipid synthesis pathway.
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 217.
Abstract 2171: Viral infection as an etiological risk factor for diffuse large B cell lymphoma (DLBCL): A comparative study between Egypt and Sweden
Authors: Jacobson Therese AS , Bahnassy Abeer A. , Moshfeg Ali , Zekri Abdel Rahman N. , Porwit Anna Porwit , Lundahl Joachim , Mokhtar Nadia M. , Abdel-Hamid Nayera A. , Khaled hussein M. , Mellstedt Håkan 
Published: February 2011

Abstract
Objective: Previous studies have reported an association between increased risk of diffuse large B cell lymphoma (DLBCL) and hepatitis B, hepatitis C, Epstein Barr viruses infection in some countries including Egypt. We therefore assume that the progression of DLBCL might be enhanced by chronic viral infection and that specific pathways can be targeted for the prevention and therapy of DLBCL. Our aim is to assess the possible role of viral infections in the development and progression of DLBCL by determining the genetic profile of DLBCL cases from areas with different prevalence of viral infection. Methods: Gene expression profile of well-characterized cases of DLBCL (30 from Egypt and 16 from Sweden) together with their normal matched controls was studied using the Affymetrix Human GeneShip U133 plus 2.0. Data sets were assigned to two groups (Swedish and Egyptian) and the expression profiles were compared to identify genes that were differentially expressed between the groups. Lists were compiled of all genes for which expression was differentially either induced or suppressed &gt;2-fold between groups. The gene lists were categorized according to their biological functions as described in GeneSpring and Ingenuity. Validation studies were done using RT-PCR, in situ hybridization and immunohistovhemistry. Results: After statistical analysis and filtration by fold change more than 2 times, 2790 genes entities were differentially expressed in the two groups. 1) STAT 2 was highly expressed in Swedish patients and the difference between the two patient groups is clearly indicated in the IFN signaling pathway, 2) higher expression of antigen presentation gene in Egyptian patients compared to Swedish patients (HLA-DQA1, HLA-B, MHCIIα, MHCIα), and 3) higher expression genes in wnt signaling pathway in Egyptian patients compared to Swedish patients (wnt7A, β catenine, CK1). Conclusions: Chronic viral infection could be a risk factor for DLBCL in Egypt (which represents an area with high prevalence of viral infection) but not in Sweden.
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 2171.
Abstract 2182: Differential transfection on a cell chip for high throughput analysis of paracrine gene effects in angiogenesis and tumor invasion
Authors: Kuhn Elisabeth , Naschberger Elisabeth , Konrad Andreas , Croner Roland S. , Münstedt Helmut , Stürzl Michael 
Published: February 2011

Abstract
Introduction: Tumor invasion and angiogenesis are key processes in tumor progression. Previously, transcriptome analyses identified numerous genes which are associated with tumor progression. The role of these genes in tumor invasion and angiogenesis is mostly unknown. Here we describe for the first time a cell chip-based high throughput analysis of paracrine gene functions in tumor invasion and angiogenesis.
Method: Expression plasmids of tumor progression-associated genes, gelatin and transfection reagent were spotted onto slides using a microarray robot. Subsequently mixtures of tumor cells and target cells (e.g. endothelial cells for angiogenesis, fibroblasts for tumor invasion) were seeded onto the slides. The conditions were adjusted that exclusively the tumor cells but not the target cells got transfected. Restriction of paracrine activities on the different transfection spots was achieved by an overlay with appropriate polymer matrices to decrease spot to spot diffusion. Immunocytochemical detection of the proliferation marker Ki67 and matrix metalloproteinases in the target cells indicated paracrine activities of transfected genes on angiogenesis (increased endothelial cell proliferation) and invasion (increased expression of matrix metalloproteinases in fibroblasts).
Results: Using epithelial tumor cells and fibroblasts the differential transfection on the cell chip could be successfully established. Model experiments with ectopic expression of IFN-gamma in the tumor cells and the detection of IFN-gamma-induced genes in fibroblasts showed that paracrine gene effects could be sensitively detected. An overlay with polymeric matrices restricted locally the diffusion of IFN-gamma on the respective transfection spots. With this method 150 transfections could be carried out on a single chip in order to investigate paracrine gene functions.
Conclusion: Differential transfection on a cell chip provides a novel and efficient high throughput technology to determine paracrine gene functions in angiogenesis and tumor invasion.
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 2182.