bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2005: Analysis of gene expression and copy number variation in breast tumors using both sequencing and hybridization-based platforms.
Authors: Norton Nadine , Perez Edith A. , Asmann Yan W. , Carr Jennifer M. , Necela Brian M. , Kachergus Jennifer M. , Jen Jin , Eckloff Bruce W. , Thompson E Aubrey 
Published: August 2014

Abstract
Next Generation Sequencing (NGS) technologies provide rapid genomic analyses of single nucleotide variants, RNA expression and DNA copy number. Application of these technologies to material isolated from formalin fixed paraffin embedded (FFPE) tissue and even degraded frozen material could provide powerful replication samples but remains challenging. We tested the nanoString platform to validate deep sequence analysis of gene expression and DNA copy number in degraded and FFPE material. Firstly, RNA from the Universal Human Reference RNA and a breast cancer cell line (MDA-MB-436) was artificially degraded to different degrees (RIN 1.2-6.8). We used the nanoString platform to simultaneously measure RNA expression across 226 genes in each degraded sample and the corresponding undegraded RNA. Secondly we isolated RNA and DNA from matched fresh frozen and FFPE tissues from nine breast cancer patients (3 HER2+/ER+/PR+, 2 HER2+/ER-/PR-, 2 HER2+/ER+/PR-, 2 HER2-/ER+/PR+) using the nanoString platform to compare expression and copy number across 226 and 86 genes respectively. Finally, we correlated expression and copy number data generated by nanoString with Illumina transcriptome and whole genome sequencing (WGS). NanoString log2 expression fold-change between all artificially degraded samples and their undegraded counterpart showed extremely high correlation (r2&gt;0.91). NanoString DNA copy number between matched fresh-frozen and FFPE showed a high degree of correlation (r2=0.71). All gene amplifications with copy number ≥ 5 in DNA from fresh-frozen material (N=9) were successfully identified in DNA from FFPE material. We also observed good correlation of gene expression between whole transcriptome sequencing and the nanoString platform (r2 0.59 - 0.72) in FFPE and artificially degraded material and for DNA copy number between WGS and nanoString in DNA isolated from cancer cell lines (r2=0.96). The nanoString platform provides reliable data from highly degraded and FFPE material and correlates with sequence analysis of both expression and copy number from NGS platforms demonstrating potential for large-scale replication studies in FFPE material.
Citation Format: Nadine Norton, Edith A. Perez, Yan W. Asmann, Jennifer M. Carr, Brian M. Necela, Jennifer M. Kachergus, Jin Jen, Bruce W. Eckloff, E Aubrey Thompson. Analysis of gene expression and copy number variation in breast tumors using both sequencing and hybridization-based platforms. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2005. doi:10.1158/1538-7445.AM2013-2005
Abstract 2007: The NF-kB pathway is constitutively active in endometrial cancer.
Authors: Noonan Anne M. , Casablanca Yovanni , Maxwell George L. , Annunziata Christina M. 
Published: August 2014

Abstract
The NF-κB Pathway is Constitutively Active in Endometrial Cancer
Metastatic endometrial cancer (EC) is a disease for which therapeutic options are limited and prognosis is poor. Although 75% of endometrial cancers are diagnosed at an early stage and cured by surgery, 15-20% develop metastases and die from their disease. Uterine papillary serous carcinoma (UPSC) occurs in less than 10% of patients, but has a worse clinical outcome. Prior studies suggest that NF-kB signaling may play a role in UPSC. We therefore proceeded with a detailed investigation of the NF-κB pathway in EC.
Methods: A set of 11 endometrial cancer cell lines, representing endometrioid EC and UPSC, were tested for sensitivity to a specific inhibitor of IKKβ after 3 days of drug treatment using XTT assay. Western blot was used to assess changes in NF-κB proteins after treatment of sensitive UPSC cell lines ARK-1 and ACI-126 with IKKβ inhibitor over a time series ranging from 15 min to 24h. RNA was extracted from ARK-1 and ACI-126 cell lines after 48h treatment with IKK-2 inhibitor IV or DMSO control, and after transfection of the same cell lines with IκBα super-repressor or empty vector control. RNA was hybridized to Affymetrix U133 Plus2.0 microarray platform for gene expression profiling and the data was analyzed using mAdb. Gene and protein expression was examined in patient samples to verify biologic relevance.
Results: Six of 11 cell lines were sensitive to IKKβ inhibitor with IC50s ranging between 4 and 10uM. The highest sensitivity occurred in two UPSC cell lines ARK-1 and ACI-126. Following pharmacologic IKKβ inhibition, nuclear levels of NF-κB p65 decreased by 3h and began to increase again from 6h to 24h. Cytoplasmic NF-κB p65 increased from 15 min to 3h and then began to fall. Gene expression profiling after IKKβ inhibition, either by drug treatment or by mutant IkBa super-repressor, revealed an overlapping gene signature in the two UPSC cell lines. The genes were co-expressed across the gene expression profiles of patients with EC, and were significantly highest in African American women with UPSC.
Conclusions: There is aberrant signaling through the NF-κB pathway in a subset of EC. An IKKβ target gene signature shows that this pathway is most relevant in African American women with UPSC. Therefore, targeting NF-kB may provide a novel treatment strategy for this underserved population with a rare variant of EC.
Citation Format: Anne M. Noonan, Yovanni Casablanca, George L. Maxwell, Christina M. Annunziata. The NF-kB pathway is constitutively active in endometrial cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2007. doi:10.1158/1538-7445.AM2013-2007
Abstract 201: (-)-Epigallocatechin-3-gallate inhibits the development of hepatic preneoplastic lesions in obese and hypertensive rats, a novel model of non-alcoholic steatohepatitis-related liver tumorigenesis.
Authors: Kochi Takahiro , Shimizu Masahito , Tanaka Takuji , Moriwaki Hisataka 
Published: August 2014

Abstract
Background: Non-alcoholic steatohepatitis (NASH), which involves hepatic inflammation and fibrosis, is associated with liver carcinogenesis. The activation of the renin-angiotensin system (RAS), which plays a key role in blood pressure regulation, promotes hepatic fibrogenesis. In this study, we investigated the effects of (-)-epigallocatechin-3-gallate (EGCG), a major component of green tea catechins, on the development of hepatic preneoplastic lesions in SHRSP.Z-Leprfa/IzmDmcr (SHRSP-ZF) obese and hypertensive rats. Methods: Male 7-week-old SHRSP-ZF rats and control non-obese and normotensive WKY/Izm rats were fed a high fat diet and received intraperitoneal injections of carbon tetrachloride twice a week for 8 weeks. The rats were also provided tap water containing 0.1% EGCG during the experiment. Results: SHRSP-ZF rats presented with obesity, insulin resistance, dyslipidemia, an imbalance of adipokines in the serum, and hepatic steatosis. The development of hepatic preneoplastic lesions and liver fibrosis was markedly accelerated in SHRSP-ZF rats compared to that in control rats. Additionally, in SHRSP-ZF rats, RAS was activated and inflammation and oxidative stress were induced. Administration of EGCG, however, inhibited the development of hepatic premalignant lesions by improving liver fibrosis, inhibiting RAS activation, and attenuating inflammation and oxidative stress in SHRSP-ZF rats. Conclusions: Obese and hypertensive SHRSP-ZF rats treated with a high fat diet and carbon tetrachloride displayed the histopathological and pathophysiological characteristics of NASH and developed hepatic premalignant lesions, suggesting the model might be useful for the evaluation of NASH-related liver tumorigenesis. EGCG might also be able to prevent NASH-related liver fibrosis and tumorigenesis.
Citation Format: Takahiro Kochi, Masahito Shimizu, Takuji Tanaka, Hisataka Moriwaki. (-)-Epigallocatechin-3-gallate inhibits the development of hepatic preneoplastic lesions in obese and hypertensive rats, a novel model of non-alcoholic steatohepatitis-related liver tumorigenesis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 201. doi:10.1158/1538-7445.AM2013-201
Abstract 2012: Ultra-deep sequencing of circulating free DNA to identify predictive, mutated HSP90 clients in the GALAXY TrialTM (NCT01348126): a randomized phase IIB/III study of ganetespib (STA-9090) in combination with docetaxel versus docetaxel alone in subjects wit
Authors: Fennell Dean Anthony , Martins L. Miguel , El-Hariry Iman , Vukovic Vojo , Teofilovici Florentina , Reichert Vienna L. , Shaw Jacqui 
Published: August 2014

Abstract
Background: Non-small cell lung cancer is a mosaic, comprising several distinct molecular subtypes driven by somatic mutations in so-called cancer genes. Several of these oncogenic mutations confer dependence on HSP90 e.g. EML4-ALK, BRAF, KRAS, KIT. Inhibition of Hsp90 induces apoptosis and can exploit this dependence. Ganetespib (G) is an Hsp90 inhibitor with single agent activity in molecularly defined disease, including EML4-ALK rearrangement, KRAS mutations, HER2 amplification and BRAF mutations. Circulating free DNA (cfDNA) is present at low levels in plasma of healthy individuals allowing detection of somatic mutations by deep sequencing. The aim of this work was to determine the mutational spectrum of patients enrolled into the GALAXY trial using this liquid biopsy strategy.
Methods: We performed a prospective exploratory analysis to identify plasma-borne somatic mutations as predictors of clinical outcome with G in GALAXY, a randomized trial, comparing G + docetaxel (D), to D alone in 2nd line advanced NSCLC patients. Plasma samples were collected from approximately 200 patients with adenocarcinoma at baseline prior to initiation of treatment, and during cycles 1 and 2. cfDNA samples were evaluated using the Ion AmpliSeq™ Cancer Panel on the Ion Torrent |PGM platform to survey 739 amplicons in 46 cancer genes at up to 6000x depth.
Results: CfDNA targeted sequence analysis of the first 38 patients revealed multiple concurrent mutations in client proteins including the HSP90 client proteins BRAF, PDGFR and KIT, demonstrating the feasibility of this method. Sequencing of a larger cohort is underway. Longitudinal sampling of plasma has been conducted to monitor temporal evolution of the penetrance of mutations.
Summary: Ultra-deep re-sequencing of multiple somatic mutations in circulating cfDNA is feasible, and can potentially enable identification of G sensitive subgroups. This represents a new approach to biomarker discovery in the context of phase II trials.
Citation Format: Dean Anthony Fennell, L. Miguel Martins, Iman El-Hariry, Vojo Vukovic, Florentina Teofilovici, Vienna L. Reichert, Jacqui Shaw. Ultra-deep sequencing of circulating free DNA to identify predictive, mutated HSP90 clients in the GALAXY TrialTM (NCT01348126): a randomized phase IIB/III study of ganetespib (STA-9090) in combination with docetaxel versus docetaxel alone in subjects wit [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2012. doi:10.1158/1538-7445.AM2013-2012
Abstract 2017: Exome sequencing reveals novel mutations in a GIST and a paraganglioma occurring simultaneously in a patient with complete form of Carney triad.
Authors: Haller Florian , Agaimy Abbas , Moskalev Evgeny A. , Jäger Natalie , Broers Benedikt , Wiemann Stefan , Hartmann Arndt 
Published: August 2014

Abstract
Carney triad is a rare syndrome which is defined by the occurrence of multicentric gastric GIST, paraganglioma and pulmonary chondroma. In contrast to the closely-related Carney-Stratakis syndrome (CSS), Carney syndrome is not inherited. In both syndromes, the tumors are characterized by a loss of Succinate Dehydrogenase B protein (so-called SDHB-deficient tumors). Only recently, inactivating mutations in the SDH subunits A, B, C, and D have been found to be present in the majority of SDHB-deficient GISTs of CSS, but not in GISTs in the setting of Carney triad. We performed exome sequencing of DNA samples derived from blood as well as of the GIST and the paraganglioma from a female patient with a complete Carney triad. Additionally, the genome from the blood DNA was sequenced at high coverage, and low coverage genomes of both tumor DNAs were evaluated for copy number variations. SDHA and B mRNA and protein expression were analysed by qRT-PCR and Western Blot analysis, respectively. Both the GIST and the paraganglioma from the Carney patient were negative for SDHB by immunohistochemistry, and did not display noticeable levels of SDHB in the Western Blot analysis. In contrast, SDHB mRNA levels were equal to SDHA levels, and also to GISTs from sporadic GISTs with KIT mutations. Exome sequencing revealed 10 and 18 somatic missense mutations in the DNA from the GIST and the paraganglioma, which were not present in the DNA from the blood. Additionally, one somatic insertion/deletion was found in each tumor. These novel mutations will provide better insights in our understanding of this rare albeit fascinating disease, and might also be suitable as targets for future therapies.
Citation Format: Florian Haller, Abbas Agaimy, Evgeny A. Moskalev, Natalie Jäger, Benedikt Broers, Stefan Wiemann, Arndt Hartmann. Exome sequencing reveals novel mutations in a GIST and a paraganglioma occurring simultaneously in a patient with complete form of Carney triad. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2017. doi:10.1158/1538-7445.AM2013-2017
Abstract 2018: Genome-wide analysis of DNA methylation and copy number changes in breast cancers.
Authors: Stefansson Olafur A. , Moran Sebastian , Gomez Antonio , Puig Sergi Sayols , Eyfjord Jorunn , Esteller Manel 
Published: August 2014

Abstract
Epigenetic modifications are known to be critical in regulating normal developmental processes and cellular differentiation. DNA methylation of CpG dinucleotides is a well-characterized epigenetic marker frequently associated with transcriptional silencing. CpG dinucleotides are non-randomly distributed throughout the genome with regions enriched for CpGs being known as CpG islands. It is now well established that epigenetic inactivation of tumor suppressor genes can occur by CpG island promoter methylation. For example, BRCA1 promoter methylation occurs in approximately 10 - 15% of all breast cancers and is associated with gene silencing. Recent technological advances have enabled DNA methylation to be profiled genome-wide. Using the Infinium 450 thousand probe arrays, we have studied DNA methylation and copy number changes to discover new markers of potential clinical relevance in breast cancer. Expression analyses by immunohistochemisty on tissue arrays for subtype-specific markers (ER, PR, HER2, Ki-67, EGFR, CK5/6, CK8, CK18, MUC1 and Claudin-3) carried out previously were used to establish DNA methylation markers of breast cancer subtypes. This integrated approach is presented in clinical context with available data on histological grade, disease stage and breast cancer-specific survival outcomes.
Citation Format: Olafur A. Stefansson, Sebastian Moran, Antonio Gomez, Sergi Sayols Puig, Jorunn Eyfjord, Manel Esteller. Genome-wide analysis of DNA methylation and copy number changes in breast cancers. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2018. doi:10.1158/1538-7445.AM2013-2018
Abstract 2020: Next-generation sequencing for mutation discovery in Ewing sarcoma.
Authors: Brohl Andrew S. , Song Young , Hurd Laura , Liao Hongling , Chen Li , Patidar Rajesh , Shern John F. , Wei Jun S. , Khan Javed 
Published: August 2014

Abstract
Background: Ewing sarcoma (EWS) is the second most common type of primary bone tumor to affect children and adolescent and accounts for 2.9% of all childhood cancers. Despite advances in multidisciplinary treatment leading to improved outcomes over time, long term survival still remains less than 50% for patients older than 15 years of age and only 65% in younger patients. In an effort to identify novel prognostic and therapeutic targets, we utilized next generation sequencing techniques to evaluate EWS samples for somatic mutation.
Methods: Whole genome paired-end sequencing using the Complete Genomics method was performed on the DNA from 6 EWS matched tumor-normal samples. Somatic mutations were identified and classified using standard bioinformatics techniques and mutations of interest were verified using capillary sequencing. To extend discoveries and evaluate for mutational recurrence, targeted sequencing was performed on a validation cohort of 61 EWS tumors and 22 EWS cell lines using a custom multiplex PCR design followed by high-coverage sequencing on the Ion Torrent system.
Results: In the discovery cohort, we detected an average of 361 somatic mutations per tumor in non-repetitive regions and an average of 6 somatic mutations per tumor in protein coding regions (=0.15 mutations/Mb of coding sequence). The well-established FLI1-EWSR1 gene fusion was detected by the whole genome sequencing in all 6 samples. Additional previously reported genetic events were also seen including frequent chromosomal trisomy and deletion of the CDKN2A containing locus on chromosomal region 9p21 in 2 of 6 samples. In the validation cohort of tumors, known recurrent mutations such as in TP53 (3/61 = 4.9%) were seen at rates similar to that previously reported in EWS. Continued efforts are underway to verify novel recurrent mutations.
Conclusion: Next-generation sequencing provides a powerful tool to characterize the genetic landscape and evaluate for recurrent mutations in cancer. We utilize this tool in Ewing sarcoma in a project that provides both a comprehensive genomic evaluation from whole genome sequencing data and as well evaluates for recurrent mutations using a targeted sequencing approach.
Citation Format: Andrew S. Brohl, Young Song, Laura Hurd, Hongling Liao, Li Chen, Rajesh Patidar, John F. Shern, Jun S. Wei, Javed Khan. Next-generation sequencing for mutation discovery in Ewing sarcoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2020. doi:10.1158/1538-7445.AM2013-2020
Abstract 2021: Characterization of myeloma tumors from a multi-ethnic cohort using cytogenetics and genomic analysis.
Authors: Baker Angela S. , Braggio Esteban , Jacobus Susana , Jung Sungwon , Larson Dirk , Therneau Terry , Dispenzieri Angela , Van Wier Scott A. , Ahmann Gregory , Levy Joan , Perkins Louise , Kim Seungchan , Henderson Kim , Vesole David , Rajkumar S. Vincent , Jelinek Dianne F. , Carpten John , Fonseca Rafael 
Published: August 2014

Abstract
The plasma cell malignancy Multiple Myeloma (MM) is a rare but deadly form of cancer with 5 year survival rates of ∼30%. Epidemiological studies have suggested that MM exacts an especially heavy burden on African American (AA) patients. We examined a multi-ethnic cohort of MM tumors to assess potential differences in the frequency of molecular events in tumors derived from either African American (AA) or European American (EA) patients. The frequency of 14q32 translocation breakpoints at the IgH locus was compared among a series of data from 115 AA MM patients from three studies and EA MM from the Eastern Cooperative Oncology Group (ECOG). In addition, we analyzed matching genome-wide copy number and transcriptional data among 45 AA MM tumors and 196 EA MM tumors to determine differences in the frequency of molecular events in tumors from these populations.
No differences were found for specific translocation subtypes; however, we detected a statistically significant difference in the overall frequency of IgH translocations between the two groups, which occurred more frequently in EA patients (52% vs. 40%; p = 0.032). When assessing genomic copy number events previously shown to be associated with poor outcome in MM, frequencies of alterations were not significant after correcting for multiple testing. Furthermore, there was not a significant difference in the association of high-risk disease using expression profiling. Our study represents the first comprehensive assessment of the frequency and distribution of molecular alterations in MM tumors from both AA and EA patients and could help shed light on possible biological features associated with population differences in incidence and outcome in MM.
Citation Format: Angela S. Baker, Esteban Braggio, Susana Jacobus, Sungwon Jung, Dirk Larson, Terry Therneau, Angela Dispenzieri, Scott A. Van Wier, Gregory Ahmann, Joan Levy, Louise Perkins, Seungchan Kim, Kim Henderson, David Vesole, S. Vincent Rajkumar, Dianne F. Jelinek, John Carpten, Rafael Fonseca. Characterization of myeloma tumors from a multi-ethnic cohort using cytogenetics and genomic analysis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2021. doi:10.1158/1538-7445.AM2013-2021