bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 111: Recurrent mutations of CDKN2A genes characterize worse prognosis of HPV positive and negative oropharyngeal squamous cell carcinoma
Authors: Lee Jongkeun , Hong Dongwan , Lee Eun Kyung , Jung Yuh-Seog , Park Weon Seo 
Published: July 2016

Abstract
Background: Oropharyngeal squamous cell carcinoma (OSCC) exhibits unique clinical and molecular characteristics, depending on its association with high-risk human papillomavirus (HPV) or other carcinogen like smoking1. Considering significant subset of patients with OSCC still exhibits poor response to contemporary treatments2, which frequently cause significant toxicity, a more detailed understanding of these poor responders, especially adopting current precision genomic technology, could provide a clue for developing better treatment.
Methods: In this study, we gathered the somatic point mutations and mRNA expression data of 520 OSCC patients from The Cancer Genome Atlas (TCGA) and then investigated recurrent somatic point mutations. To genes having the recurrent and same type point mutations, in addition, we check out the mRNA expression and analyzed a survival analysis.
Results: We found 7 somatic point mutations of CDKN2A gene, which having recurrent patients and only nonsense SNVs. Out of these mutation, 6 recurrent point mutations of CDKN2A gene have highly expressed on PIK3CA, FGFR2 and FGFR3 genes, as well as showed a significant deterioration on survival outcome.
Conclusion: Recurrent nonsense mutations of CDKN2A mostly (6/7, 85.7%) derived an abnormal regulation of other genes, such as PI3KA, FGFR2, and FGFR3. Moreover, this pattern of mutations significantly characterizes ominous prognosis in HPV positive and negative OSCC. Our result might provide better insights for characterizing the subgroup of OSCC and eventual development of precision strategy for this disease subset.
References
1. Licitra, L. et al. High-risk human papillomavirus affects prognosis in patients with surgically treated oropharyngeal squamous cell carcinoma. J Clin Oncol 24, 5630-6 (2006).
2. Ang, K.K. et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 363, 24-35 (2010).
Citation Format: Jongkeun Lee, Dongwan Hong, Eun Kyung Lee, Yuh-Seog Jung, Weon Seo Park. Recurrent mutations of CDKN2A genes characterize worse prognosis of HPV positive and negative oropharyngeal squamous cell carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 111.
Abstract 1110: Inhibition of histone deacetylase induces miR-320-mediated androgen receptor suppression in prostate cancer
Authors: Sato Shinya , Katsushima Keisuke , Shinjo Keiko , Takahashi Satoru , Kondo Yutaka 
Published: July 2016

Abstract
Targeting androgen receptor (AR) by pharmacological intervention is one of the effective approaches for treatment of malignant prostate cancers. Histone deacetylase (HDAC) alters epigenetic status of tumor-associated genes, including microRNAs (miRNAs), and affects the behavior of cancers. Here we examined molecular effects of a HDAC inhibitor, OBP-801, on AR expression and tumor cell growth in prostate cancers. Treatment of OBP-801 efficiently suppressed cell growth of three prostate cancer lines (22Rv1, VCaP, and LNCaP), together with AR downregulation, regardless of their hormone sensitivity. Intriguingly, this effect by OBP-801 is not due to downregulation of transcriptional activity of the AR gene, but due to post-transcriptional regulation, namely miRNA-mediated suppression. Among the upregulated miRNAs after OBP-801 treatment in three prostate cancer cell lines, miR-320a, of which expression was significantly correlated with prognosis of prostate cancers (P = 0.0185), was the most closely associated with AR expression. miR-320a mimic suppressed AR protein expression together with growth suppression, while anti-miR320a significantly abrogated the growth suppression by OBP-801 treatment. Fluorescent in situ hybridization analysis revealed that miR-320a was highly expressed in human normal prostate luminal cells but rarely expressed in prostate cancer cells. In AR-dependent prostate tumorigenic rat model, OBP-801 treatment profoundly increased the miR-320 expression and repressed prostate tumorigenesis. Our data demonstrated that OBP-801 effectively suppressed AR activity via epigenetic upregulation of miR-320a, which resulted in tumor cell growth suppression of prostate cancers. OBP-801 may be a potent drug as an AR targeting therapy in AR positive prostate cancer regardless of androgen dependency.
Citation Format: Shinya Sato, Keisuke Katsushima, Keiko Shinjo, Satoru Takahashi, Yutaka Kondo. Inhibition of histone deacetylase induces miR-320-mediated androgen receptor suppression in prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1110.
Abstract 1112: miR-550a-x fuctions as a tumor suppressor by inhibiting the oncogenic YAP1 in human cancers
Authors: Choe Min Ho , Kim Joon , Han Young-Hoon , Kim Jae-Sung 
Published: July 2016

Abstract
Although Yes-associated protein 1 (YAP1), an essential downstream effector of hippo pathway, is a potent oncogene and amplified in human cancers, the overexpression mechanism is unclear. Herein, this study shows that miR-550a-x directly inhibits the oncogenic YAP1 and functions as a tumor suppressor in various human cancer cells. Ectopic overexpression of miRNA-550a-x suppressed proliferation and survival of various cancer cells via inducing apoptosis. miR-550a-x also had a capacity to suppress cell migration, epithelial-mesenchymal transition and tumor sphere formation. Using bioinformatics and microarray analysis, we found YAP1 as a putative target gene. miR-550a-x decreased the mRNA and protein levels of YAP1 in various cancer cells and significantly repressed YAP1 activity with its downstream target genes including CTGF and CYR61. The expression level of miRNA-550a-x were inversely correlated with the YAP1 expression in normal and colorectal cancer samples. Therefore, our data suggest that miRNA-550X functions as a tumor suppressor by targeting YAP1, which may provide a novel therapeutic option for cancer treatment.
Citation Format: Min Ho Choe, Joon Kim, Young-Hoon Han, Jae-Sung Kim. miR-550a-x fuctions as a tumor suppressor by inhibiting the oncogenic YAP1 in human cancers. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1112.
Abstract 1113: Mir-194-3p suppresses tumorigenic potential of glioblastoma stem cells by targeting the canonical NF-kB pathway
Authors: Singh Rajbir , Palanichamy Kamalakannan , Jacob John R. , Chakravarti Arnab 
Published: July 2016

Abstract
Glioblastoma (GBM) is the most common tumor of the central nervous system, with its deadly nature owing to high rates of invasion and angiogenesis. A key element in its pathogenesis is a small subpopulation of neoplastic cells called glioma stem cells (GSCs) that are responsible for tumor initiation, maintenance and relapse. Approaches to target GSCs have mostly proved futile due to their chemo- and radio-resistance potential. Given that microRNAs carry a potential to affect both normal and stem cells, we employed a microRNA-based targeted approach to identify the subset of microRNAs that could distinctively affect the stemness of GSCs. Our study tests the hypothesis that GSCs will show an altered miRNA expression upon their differentiation, and their profiling may lead to identification of specific microRNAs that regulate the process. Our initial efforts resulted in identification of hsa-miR-194-3p as one of the potential candidates, which was consistently downregulated in multiple GSCs that we investigated. Stable cell lines overexpressing hsa-miR-194-3p showed a decreased proliferation rate and reduced sphere-forming ability. In silico analysis revealed TAB2, an upstream activator of NF-κB pathway to be the potential target of hsa-miR-194-3p, which was confirmed by luciferase assay and knockdown approaches. The regulatory role of hsa-miR-194-3p was substantiated by its ability to inhibit the NF-κB pathway and the corresponding downstream targets including IL-6 and STAT3. In vivo studies revealed a reduced tumor forming ability when the cell lines overexpressing hsa-miR-194-3p were injected intracranially in NOD/SCID mice, compared with the non-target control. Our results indicate that hsa-miR-194-3p blocked the canonical NF-κB signaling and negatively affected tumor formation. We have carried out this study this in a unique model system expecting it to uncover another layer of complexity that may add a new facet to meet the challenge imposed by the cancer stem cell paradigm. In conclusion, we accentuate the anti-tumorigenic role of hsa-miR-194-3p as a connecting link to both stemness and NF-κB signaling.
Funding sources: This work was supported by R01CA108633 (To AC), 1RC2CA148190 (To AC) U10CA180850-01 (To AC), 1R01CA169368 (To AC) from the National Cancer Institute (NCI), Brain Tumor Funders Collaborative Grant (To AC), Ohio State University Comprehensive Cancer Center Award (To AC).
Citation Format: Rajbir Singh, Kamalakannan Palanichamy, John R. Jacob, Arnab Chakravarti. Mir-194-3p suppresses tumorigenic potential of glioblastoma stem cells by targeting the canonical NF-kB pathway. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1113.
Abstract 1119: Tumor suppressing dual-action miRNA: Targeting Warburg effect and androgen receptor function in CRPC
Authors: Ebron Jey Sabith , Singh Jagjit , Sikand Kavleen , Shankar Eswar , Gupta Sanjay , Shukla Girish C. 
Published: July 2016

Abstract
The ability of prostate cancer cells to alter their metabolism in a manner distinct from benign cells and energy reprogramming is a major concern in treatment of castration resistant prostate cancer (CRPC). On the other hand, development of resistance to next-generation drugs directed against the AR signaling axis (Abiraterone acetate and Enzalutamide) confers a grim prognosis. Hence, targeting aerobic glycolysis of tumor cells as well as AR signaling axis in CRPC is highly desirable. Here, we report the role of a dual-action miRNA which targets the Androgen Receptor function as well as action of key factors involved in tumor energy metabolism. In addition, the miRNA also targets the key anti-apoptotic factors and enhance the apoptosis in cultured cells. Furthermore, together with Enzalutamide, the miRNA shows a potent synergistic anti-tumor activity in 22RV1 mouse xenografts. We will present the detailed results showing the therapeutic potential of dual-action miRNA in the treatment of CRPC.
Citation Format: Jey Sabith Ebron, Jagjit Singh, Kavleen Sikand, Eswar Shankar, Sanjay Gupta, Girish C. Shukla. Tumor suppressing dual-action miRNA: Targeting Warburg effect and androgen receptor function in CRPC. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1119.
Abstract 1120: Differential expression of human cytomegalovirus microRNA in triple-negative breast cancer tumors
Authors: Hudson Tia , Harrison Scott , K C Dukka , Prins Jan , Muganda Perpetua M. 
Published: July 2016

Abstract
Triple-negative breast cancer (TNBC) accounts for 15-20% of the breast cancer cases.
These tumors are heterogeneous and aggressive, fail to respond to targeted therapy, have poor prognosis, and a high risk of relapse. The molecular basis of this breast cancer subtype is currently unknown. Viruses, such as human cytomegalovirus (HCMV), Epstein-Barr virus (EBV), and human papillomavirus (HPV), are major suspects in the etiology of breast cancer. Since miRNAs have been implicated in the pathogenesis of breast cancer, including triple-negative breast cancer, we hypothesized that viral miRNAs may play a role in this aggressive disease. The objective of this project, therefore, was to determine the identity, prevalence, sequence variation, and differential expression of viral miRNAs in TNBC tumors as compared to control samples. We conducted a comprehensive profiling of viral miRNAs in 48 TNBC tumors as compared to 15 control normal breast tissues, utilizing deep sequencing analysis software and publically available deep sequencing data. Five novel putative HCMV miRNAs were found to be differentially expressed in TNBC tumors as compared to controls. Two of the putative miRNAs were differentially expressed in 60-79% of the TNBC tumors as compared to 0% of normal controls. Two additional putative miRNAs were expressed in 67-88% of TNBC tumors as compared to 25-31% of normal controls. One putative miRNA was expressed in 67% of TNBC tumors as compared to 88% of normal samples, while 1 putative miRNA in addition to HCMV-US25-1-3p displayed no significant differences. These putative HCMV miRNAs localize within genomic regions of HCMV that encode UL56 DNA packaging terminase subunit 2, single-stranded DNA-binding protein, noncoding RNA4.9, and enveloped glycoprotein M. Ongoing work has so far computationally validated one of these miRNAs as a novel HCMV miRNA. This is the first report on the differential expression of HCMV miRNAs in TNBC tumors. Since TNBC tumors are extremely heterogeneous, it is intriguing that 60-80% of TNBC tumors specifically express the same HCMV miRNA. Our findings suggest that these differentially expressed HCMV miRNAs may potentially play a role in the pathogenesis of TNBC.
Citation Format: Tia Hudson, Scott Harrison, Dukka K C, Jan Prins, Perpetua M. Muganda. Differential expression of human cytomegalovirus microRNA in triple-negative breast cancer tumors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1120.
Abstract 1127: KIT/D816V induces SRC-mediated tyrosine phosphorylation of MITF and altered transcription program in melanoma
Authors: Phung Bengt , Kazi Julhash U. , Lundby Alicia , Bergsteinsdottir Kristin , Sun Jianmin , Goding Colin R. , Jönsson Göran , Olsen Jesper V. , Steingrímsson Eiríkur , Rönnstrand Lars 
Published: July 2016

Abstract
The oncogenic D816V mutation of the KIT receptor is well characterized in systemic mastocytosis and acute myeloid leukemia. Although KITD816V has been found in melanoma, its function and involvement in this malignancy is not understood. Here we show that KITD816V induces tyrosine phosphorylation of the microphthalmia-associated transcription factor (MITF) through a triple protein complex formation between KIT, MITF and SRC family kinases. In turn, phosphorylated MITF activates target genes that are involved in melanoma proliferation, cell cycle progression, suppression of senescence, survival and invasion. By blocking the triple protein complex formation, thus preventing MITF phosphorylation, the cells become hypersensitive to SRC inhibitors. We have therefore delineated the mechanism behind the oncogenic effects of KITD816V in melanoma and provide a rationale for testing SRC family kinase inhibitors to treat KITD816V-transformed melanomas.
Citation Format: Bengt Phung, Julhash U. Kazi, Alicia Lundby, Kristin Bergsteinsdottir, Jianmin Sun, Colin R. Goding, Göran Jönsson, Jesper V. Olsen, Eiríkur Steingrímsson, Lars Rönnstrand. KIT/D816V induces SRC-mediated tyrosine phosphorylation of MITF and altered transcription program in melanoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1127.
Abstract 1131: Uncovering oncogenic KRAS allele specific phenotypes using an isogenic MEF cell line system
Authors: Fer Nicole , Smith Brian , Garvey Leslie , Burgan William , Powell Katie , Sharma Kanika , Waters Andrew , Wu Xiaolin , Soppet Dan , Stephens Robert , Nissley Dwight , Holderfield Matthew , Bagni Rachel K. 
Published: July 2016

Abstract
The RAS Initiative at the Frederick National Laboratory has generated an isogenic mouse embryonic fibroblast (MEFs) cell line panel containing single transgene alleles using the RAS-less MEF system developed by Matthias Drosten and Mariano Barbacid (CNIO). These MEFs are H, N and K-RAS null, growth is dependent on exogenous RAS or MAPK pathway activation. The panel includes: KRAS 4A WT, KRAS 4B WT, KRAS 4B G12C, G12D, G12V, G13D, Q61L, Q61R, HRAS WT, NRAS WT or BRAF V600E. The workflow to generate the lines requires cre-lox removal of endogenous KRAS and the cells arrest in the G1 phase of the cycle. Proliferation is resumed through the delivery of the transgene to the cells using lentiviral transduction. Clonal cell lines are derived from the initial pools and are thoroughly characterized including confirmation of endogenous KRAS gene removal, identification of the transgene insertion site(s), calculation of proliferation rates and doubling times, analysis of signaling pathways, response to tool compounds and exome sequenced to exclude lines with mutations in onco-relevant genes. This panel is a unique resource that can be used to ask allele and isoform specific questions (gene expression profiles, GTP-loading, etc.) and screen for RAS inhibitors as well as determine novel compound specificity. This panel is available to the academic RAS research community.
Citation Format: Nicole Fer, Brian Smith, Leslie Garvey, William Burgan, Katie Powell, Kanika Sharma, Andrew Waters, Xiaolin Wu, Dan Soppet, Robert Stephens, Dwight Nissley, Matthew Holderfield, Rachel K. Bagni. Uncovering oncogenic KRAS allele specific phenotypes using an isogenic MEF cell line system. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1131.
Abstract 114: Oncogenomic analysis of Merkel cell carcinoma
Authors: Gelb Tara , Daily Kenneth , Coxon Amy , Brownell Isaac 
Published: July 2016

Abstract
We used an integrative oncogenomic approach to investigate the molecular etiology of Merkel Cell Carcinoma (MCC) in an effort to identify novel therapeutic targets and biomarkers for this highly aggressive neuroendocrine skin tumor. Because MCC is rare and poorly understood, there are currently no effective treatment options for patients with advanced disease. Approximately 80% of MCC tumors have Merkel Cell polyomavirus (MCV) DNA integrated into the host genome, and viral oncogenes are thought to drive carcinogenesis. Moreover it has been reported that MCV-negative MCC samples have an increased rate of mutations relative to MCV-positive tumors. Taken together, this suggests that MCV-positive and negative MCCs are driven by different mechanisms. We used whole exome sequencing and bioinformatic analyses to identify somatically dysregulated genes and pathways in MCC tumor samples. Additionally, we used a comparative genomic hybridization array to identify genomic amplifications and deletions. Whole transcriptome profiling was achieved using microarrays and RNA-sequencing. As the same tumor samples were used in each of these platforms, we were able to systematically correlate sequence variants with copy number changes and gene expression to identify high priority targets for further study. Interestingly, despite differences in driver mutations, we found relatively few differences in the global gene expression of MCV-positive and MCV-negative MCC tumors. Overall, our integrative oncogenomic approach has identified novel therapeutic targets for the treatment of MCC that are currently undergoing functional validation and preclinical testing.
Citation Format: Tara Gelb, Kenneth Daily, Amy Coxon, Isaac Brownell. Oncogenomic analysis of Merkel cell carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 114.
Abstract 1144: Detection of a novel ALK fusion variant in lung adenocarcinoma using a comprehensive genomic analysis
Authors: Shien Kazuhiko , Ruder Dennis , Ileana Ecaterina E. , Papadimitrakopoulou Vassiliki A. , Frampton Garrett M. , Behrens Carmen , Kalhor Neda , Lee J. Jack , Tang Ximing , Herbst Roy S. , Wistuba Ignacio I. , Izzo Julie G. 
Published: July 2016

Abstract
Background: Anaplastic lymphoma kinase (ALK) is a tyrosine kinase that is constitutively activated in a subset of non-small cell lung cancer (NSCLC), mainly as a result of chromosomal translocation. In ALK-rearranged NSCLC, the growth of tumors is strongly addicted to ALK activity, and suppression of ALK is a potent therapeutic strategy. To date, 6 known fusion partners of ALK onco-kinase have been reported in NSCLC, although the sensitivity to ALK inhibitor according to fusion variant except for EML4-ALK is still unclear. In this study, we reviewed clinical trial samples analyzed by comprehensive genomic profiling approach to detect unknown actionable ALK rearrangements.
Materials and methods: We reviewed gene alteration and expression profile of clinical samples in preliminary molecular studies from the ongoing BATTLE-2, phase II clinical trial of targeted drugs in chemo-refractory NSCLC.
Results: In 187 NSCLC samples, 3 samples harbored ALK fusion gene: 2 EML4-ALK and 1 novel ALK fusion variant PRKAR1A-ALK in a lung adenocarcinoma of male former smoker patient. The ALK gene expression levels of ALK-rearranged samples were significantly higher compared to other samples. Interestingly, the patient harboring PRKAR1A-ALK was treated with ALK inhibitor crizotinib and showed long time stable disease.
Conclusions: Our findings suggest that PRKAR1A-ALK fusion could be a novel oncogenic driver in lung adenocarcinoma and an indicator of ALK inhibitor response. (NHI-NCI CA155196; 2P50CA070907-16A1)
Citation Format: Kazuhiko Shien, Dennis Ruder, Ecaterina E. Ileana, Vassiliki A. Papadimitrakopoulou, Garrett M. Frampton, Carmen Behrens, Neda Kalhor, J. Jack Lee, Ximing Tang, Roy S. Herbst, Ignacio I. Wistuba, Julie G. Izzo. Detection of a novel ALK fusion variant in lung adenocarcinoma using a comprehensive genomic analysis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1144.