bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5572: Tracking the functional analysis of cancer risk variants
Authors: Tingle Sharna , Carrick Danielle , Schully Sheri , Clyne Mindy , Nelson Stefanie A. 
Published: August 2015

Abstract
Genome-wide association studies (GWAS) have identified thousands of alleles associated with cancer risk, but understanding the functional effects of these variants has proceeded more slowly. In addition, although catalogs of variants exist, tracking progress to determine variant function is challenging. We conducted a literature search and review to assess the trajectory of functional characterization of GWAS results and describe the types of analysis conducted and tools and databases used. We used the PubTator Web-based tool, which uses advanced text-mining techniques to accelerate manual literature curation, to search the literature for articles describing functional annotation of cancer GWAS hits. We generated a list of 646 unique SNPs from the Cancer Genomics and Epidemiology Navigator (CGEN) and imported the list to PubTator. We identified a total of 292 articles that included both variant discovery by GWAS and functional analysis, and reviewed the articles for information including cancer type, variant functional class (e.g., intron, exon, intergenic, etc.), and type of functional analysis conducted. These articles included 40 different cancer types or subtypes. The majority of cancer risk variants were intronic or intergenic, with only a small number located in coding regions. Most of the functional analyses were focused on the potential modification/disruption of regulatory processes by the risk allele (e.g., alteration of transcription factor binding sites, putative expressed quantitative trait loci), in line with current hypotheses regarding cancer risk variant function. Most studies also described effects of variants at the molecular, or cellular, rather than organismal level. We also reviewed the literature pertaining to variants identified for three cancers with possible pleiotropy - ovarian, breast, and prostate - to understand the trajectory of functional analyses beyond the initial discovery of the variants. We describe our use of the PubTator tool and provide a literature-based overview of progress in understanding the function of cancer risk variants identified via GWAS.
Citation Format: Sharna Tingle, Danielle Carrick, Sheri Schully, Mindy Clyne, Stefanie A. Nelson. Tracking the functional analysis of cancer risk variants. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5572. doi:10.1158/1538-7445.AM2015-5572
Abstract 558: Correlations of FGFR1 with ligand signaling in small-cell lung cancer
Authors: Yu Hui , Badzio Andrzej , Boyle Theresa , Lu Xian , Rivard Christopher J. , Kowalewski Ashley , Rikke Brad , Ellison Kim , Rozeboom Leslie , Hassan Biftu , Hirsch Fred R. 
Published: August 2015

Abstract
Introduction: Small cell lung cancer (SCLC) accounts for 15% of all lung cancers and has been under-studied relative to novel therapies. Signaling through fibroblast growth factors (FGF2, FGF9) and their high-affinity receptor (FGFR1) has recently emerged as a contributing factor in the pathogenesis and progression of non-small cell lung cancer (NSCLC). However, knowledge of FGFR1 and ligand expression in SCLC is limited.
Methods: FGFR1 gene copy number, mRNA levels and protein expression were determined by silver in situ hybridization (SISH), mRNA ISH and immunohistochemistry (IHC) in primary tumors from 78 SCLC patients. Expression of the ligands FGF2 and FGF9 mRNA and protein were determined by mRNA ISH and IHC, respectively. Spearman's correlations were conducted using SAS 9.4.
Results: FGFR1 protein expression by IHC demonstrated a significant correlation with FGFR1 gene copy number (p = 0.03) and FGFR1 mRNA levels (p&lt;0.0001). The positivity of FGFR1 mRNA in the SCLC cohort was 21%. FGFR1 mRNA expression correlated with both FGF2 (p = 0.0001) and FGF9 (p = 0.0018) mRNA levels, as well as with FGF2 (0.0105) and FGF9 (0.0012) protein levels. There was no significant association between FGFR1 and ligands with clinical characteristics or prognosis.
Conclusions: FGFR1 amplification and mRNA levels correlate with FGFR1 protein expression. The SCLC cohort has a substantially higher proportion of FGFR1 mRNA positive cases (21%) compared to FGFR1 gene copy number positive cases (7.8%). Combined analysis of FGFR1 and ligand expression may be valuable to determine which SCLC patients may respond to FGFR1 inhibitor therapy.
Key Words: small cell lung cancer; FGFR1; FGF2; FGF9
Citation Format: Hui Yu, Andrzej Badzio, Theresa Boyle, Xian Lu, Christopher J. Rivard, Ashley Kowalewski, Brad Rikke, Kim Ellison, Leslie Rozeboom, Biftu Hassan, Fred R. Hirsch. Correlations of FGFR1 with ligand signaling in small-cell lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 558. doi:10.1158/1538-7445.AM2015-558
Abstract 5585: Analysis of saliva samples from healthy adults in north central Florida for human papillomavirus infection
Authors: Hwang Michelle M. , Choi Hyun-Ji , Langaee Taimour Y. , Logan Henrietta L. , Raisch Kevin P. 
Published: August 2015

Abstract
Background: Prevalence rates of healthy adults shedding HPV in their saliva have varied depending on the socio-economical status of the subjects. We hypothesize that samples collected from high-poverty and low-education areas of North Central Florida will have a high prevalence of HPV positive subjects. From published studies, we would expect an infection rate of 2-10% with male and female rates being similar.
Methods: Through health fairs in North Central Florida, we consented and collected saliva from 148 healthy adults. Of the 148 study samples, 64% were between age 18-60 and 22% were above age 60. 32% of the saliva samples were from males and 68% were from females. Dividing the saliva samples by race, we had 41% white, 51% African American. DNA was isolated from the saliva samples and PCR was used to amplify HPV-specific DNA. Degenerate PCR primers were used for the PCR and sequencing the amplicons. All DNA samples were coded so the investigators do not know the identity of the samples until completion of all experiments.
Results: We optimized the degenerate primer sets, MY09/MY11 and GP5+/GP6+, for magnesium concentration and annealing temperature. In addition we optimized a nested PCR using the degenerate primers to increase the sensitivity of HPV detection. From our direct DNA sequence analysis, we identified 10/148 (7%) HPV-positive samples. HPV-types found include: 16, 12, 32, 38, 61, 83, 72, 90, and 110. The inclusion of the primer set GP5+/GP6+ with MY09/11 resulted in an increase of total HPV-positivity from 5% to 7% and the detection of high-risk HPV types 32 and 90. Of the HPV-positive saliva samples, 9% were from 18-60 year old healthy adults and 3% were from over 60-year old adults. Adult females had a similar infection rate as adult males, 7% vs. 6%. Upon comparing race, African Americans were slightly more likely to be infected than whites, 7% vs. 5%. Of the 10 adults with detectable virus in their saliva, 70% were of the high risk HPV type.
Conclusion: Our sample size was small but showed an overall infection rate of healthy adults to be similar to rates found in other studies. In our study, male and females had similar infection rates. The age 60 and younger group were found to be three times more likely to be infected than the older than age 60 group. We found no significant difference between race in our study.
Citation Format: Michelle M. Hwang, Hyun-Ji Choi, Taimour Y. Langaee, Henrietta L. Logan, Kevin P. Raisch. Analysis of saliva samples from healthy adults in north central Florida for human papillomavirus infection. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5585. doi:10.1158/1538-7445.AM2015-5585
Abstract 563: Evaluation of EGFR mutation analysis performed by Sanger sequencing versus real-time PCR (EGFR RGQ PCR Kit)
Authors: Dietmaier Wolfgang , Schardt Irene , Rümmele Petra , Geissinger Eva , Hartmann Arndt , Stöhr Robert 
Published: August 2015

Abstract
EGFR mutation analysis of exons 18, 19 and 21 is a standard analysis in routine molecular pathology for prediction of response of EGFR-tyrosine kinase inhibitors (EGFR-TKI) in non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the mutation detection using two widely used mutation analysis systems. For this purpose we analyzed exons 18, 19 and 21 of EGFR in 718 NSCLC with both nested PCR followed by direct Sanger sequencing and the EGFR RGQ PCR Kit (Qiagen). 694/718 samples were amplifiable and 676 samples allowed interpretable results by both methods. We found mutations in 74/676 (10,1%) samples by Sanger sequencing and in 91/676 (13,0%) using the RGQ Kit. There were 10/676 (1,5%) cases showing mutations only by Sanger Sequencing but not by the RGQ Kit. These mutations comprised four common EGFR-TKI sensitivity mutations in Exon21 (p.L858R (n = 2) and p.L861Q (n = 2)) as well as a complex deletion-insertion in exon 19 (n = 1). The other 5 mutations detected only by Sanger sequencing were uncommon and very rare mutations located in exon 18 and 21 which cannot be detected by the RGQ Kit due to its primer design. Vice versa, we found mutations in 21/676 samples using the RGQ Kit but not with Sanger sequencing. 20 of these mutations were common EGFR-TKI sensitivity mutations in exon 19 (deletions or complex delins, n = 15) and in exon 21 (p.L858R, n = 5) as well as a “p.G719X” mutation (n = 1) in exon 18. According to these data which includes mutations only in exons 18, 19 and 21 but not in exon 20 the mutation detection rate is higher using the RGQ-Kit than using the Sanger sequencing method (13,0% vs. 10,1%) especially in detecting common EGFR mutations associated with EGFR-TKI sensitivity. However the RGQ Kit fails in detecting uncommon and rare EGFR mutations for that this Kit is not designed and may produce non-informative results in some cases when ΔCT values are out of valid ranges whereas nested PCR followed by Sanger sequencing may still work.
Citation Format: Wolfgang Dietmaier, Irene Schardt, Petra Rümmele, Eva Geissinger, Arndt Hartmann, Robert Stöhr. Evaluation of EGFR mutation analysis performed by Sanger sequencing versus real-time PCR (EGFR RGQ PCR Kit). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 563. doi:10.1158/1538-7445.AM2015-563
Abstract 566: ChemoPlex SRM assay predicts response to specific chemotherapeutic agents in NSCLC
Authors: An Eunkyung , Kim Tae-Jung , Monga Manish , Bengali Kathleen , Drilea Alexi , Reilly Joseph , Darfler Marlene , Burrows Jon , Hembrough Todd 
Published: August 2015

Abstract
Current cancer treatment regimens rely on the use of chemotherapy agents that inhibit DNA replication and repair machinery. Several proteins are involved in this mechanism and these proteins have been identified as predictive biomarkers of response for many chemotherapy agents. While it has been demonstrated that expression levels of these biomarkers can predict chemotherapy response, chemotherapy in both the adjuvant and metastatic settings for NSCLC are not based on biomarker analysis. We have developed a quantitative, multiplex, mass spectrometry based diagnostic assay that can identify multiple biomarkers associated with chemotherapy benefit.
At the time of abstract submission, the expression levels of each biomarker were surveyed in 23 NSCLC patients, and the biomarker level for each chemotherapy agent (ERCC1 and XRCC1 for Platinum based chemotherapy; FR alpha and GART for pemetrexed; hENT1 and RRM1 for gemcitabine; and TUBB3 for taxane) was evaluated with clinical outcome. We are extending these analyses with a population of 100 NSCLC tumors with associated outcome.
Our pilot study shows a wide range of expression for each biomarker in patient biopsies. Among these biomarkers, FR alpha in NSCLC shows over 4 orders of magnitude in expression range. Also as expected, each biomarker level was found to be correlated with clinical outcome. For example, patients with high level of FR alpha showed improved response to pemetrexed; patients with lower level of TUBB3 showed improved response to taxane and patients with lower level of hENT1 showed poorer response to gemcitabine.
Our preliminary retrospective data analysis suggests that the ChemoPlex SRM assay can help predict response to specific chemotherapeutic agents. This test can be used to characterize individual tumor biology and identify actionable targets that can better inform patient care.
Citation Format: Eunkyung An, Tae-Jung Kim, Manish Monga, Kathleen Bengali, Alexi Drilea, Joseph Reilly, Marlene Darfler, Jon Burrows, Todd Hembrough. ChemoPlex SRM assay predicts response to specific chemotherapeutic agents in NSCLC. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 566. doi:10.1158/1538-7445.AM2015-566
Abstract 570: PD-L1 expression in paired non-small cell lung cancer tumor samples
Authors: Kim Jhingook , Sorensen Steffen Filskov , Choi Yoon-La , Wang Zhen (Adelle) , Sun Jong-Mu , Choi Hyejoo , Georgsen Jeanette Baehr , Dolled-Filhart Marisa , Emancipator Kenneth , Wu Dianna Y. , Meldgaard Peter , Zhou Wei , Hager Henrik 
Published: August 2015

Abstract
Background There is limited information on changes over time in programmed death ligand 1 (PD-L1) expression in non-small cell lung cancer (NSCLC).
Methods PD-L1 expression was assessed in paired tumor samples collected at different time points from the same patient using a prototype immunohistochemistry (IHC) assay with the 22C3 antibody. PD-L1 strong and weak positivity were defined to be traceable to the 1% and 50% cutoffs used in the clinical trial version of the assay. Concordance of PD-L1 expression between samples was analyzed by treating the IHC proportional score as a continuous and categorical variable.
Results 90 patients were included (73 from Korea, 17 from Denmark). 75% were male, 37% had squamous cell carcinoma, and 83% had stage I-IIIA disease. 97% of first samples and 53% of second samples were from lung. 89% and 63%, respectively, were surgical samples, with a median interval of 20.9 months (range, 0.1-94.0) between collection dates; 91% of paired samples were collected &gt;3 months apart. A significant correlation of the PD-L1 IHC proportional score was observed for the paired samples (Pearson correlation coefficient, 0.62; P &lt; 0.001). At the second time point, scores were identical in 39% of paired samples, higher in 32%, and lower in 29%. Of note, 12% of PD-L1-negative cases became positive and 20% of PD-L1-positive cases become negative at the second time point. The concordance rate was 56% (95% CI, 46%-67%) when PD-L1 expression was categorized as strong or weak positive or negative (Table).
Conclusion Although a significant correlation of the PD-L1 IHC proportional score was observed, this preliminary analysis suggested a discordance rate of 44% between initial and subsequent NSCLC tumor samples when patients were categorized by PD-L1 expression level. Similar results were observed when analyzing paired melanoma samples. This discordance should be considered if PD-L1 expression is used for selection of enrollment in clinical trials.
Table. Concordance of PD-L1 Expression in Paired NSCLC Samples (N = 90)
Later Time PointPD-L1 ExpressionStrong positive, n (%)Weak positive, n (%)Negative, n (%)Earlier Time PointStrong positive3 (3)3 (3)1 (1)Weak positive7 (8)20 (22)17 (19)Negative011 (12)28 (31)
Citation Format: Jhingook Kim, Steffen Filskov Sorensen, Yoon-La Choi, Zhen (Adelle) Wang, Jong-Mu Sun, Hyejoo Choi, Jeanette Baehr Georgsen, Marisa Dolled-Filhart, Kenneth Emancipator, Dianna Y. Wu, Peter Meldgaard, Wei Zhou, Henrik Hager. PD-L1 expression in paired non-small cell lung cancer tumor samples. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 570. doi:10.1158/1538-7445.AM2015-570
Abstract 593: Kinetic risk assessment with biomarkers of systemic inflammation in patients with metastatic renal cell carcinoma
Authors: Harris Wayne B. , Kucuk Omer , Carthon Bradley , Liu Yuan , Pattaras John , Ogan Kenneth , Master Viraj 
Published: August 2015

Abstract
Background: Empiric prognostic scoring systems for metastatic renal cell carcinoma (mRCC) are routinely employed as baseline risk stratification tools for clinical trials. However, these systems have limited clinical utility after therapeutic intervention has begun. The goal of the current study was to develop clinically useful, hypothesis-driven, kinetic risk assessment tools based exclusively on biomarkers of systemic inflammation.
Methods: A retrospective chart review was conducted with authorization from the Emory University Institutional Review Board. Inclusion criteria included treatment at the Winship Cancer Institute with a targeted agent for mRCC as well as concomitant serum C-reactive protein (CRP) and albumin levels on at least three occasions that were at least 10 days apart. The modified Glasgow Prognostic Score (mGPS) was used to quantify the intensity of systemic inflammation and to formulate the Inflammation Intensity Index for kinetic risk assessment.
Findings: Intensity of systemic inflammation was assessed 2465 times in 135 patients with cohorts used for training (n = 55; cutoff date 06/30/2012) and validation (n = 80; cutoff date 06/30/2014). Kinetic risk was assigned on the basis of time to onset of refractory systemic inflammation. The median overall survival (OS) was 44.7, 19.8, 13.0, and 6.7 months for kinetic risk categories A, B, C and D, respectively, with a median follow up of 29.3 months for the combined cohorts and none lost to follow up (censored log rank p &lt;.0001). OS was 40.6 months for whites (n = 99) vs. 9.8 months for blacks (n = 30; p &lt;.0001).
Conclusions: The correlation of dramatic differences in OS with the onset of refractory systemic inflammation provides strong evidence in support of the clinical utility of the Inflammation Intensity Index and, as a consequence, the underlying theoretical constructs, including a plausible biological hypothesis for differences in clinical outcome by race.
Citation Format: Wayne B. Harris, Omer Kucuk, Bradley Carthon, Yuan Liu, John Pattaras, Kenneth Ogan, Viraj Master. Kinetic risk assessment with biomarkers of systemic inflammation in patients with metastatic renal cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 593. doi:10.1158/1538-7445.AM2015-593
Abstract 597: Coding and noncoding gene targets in pediatric soft tissue sarcomas
Authors: Mitra Sheetal A. , Mitra Anirban P. , Buckley Jonathan D. , Triche Timothy J. 
Published: August 2015

Abstract
BACKGROUND: Genomic studies on pediatric soft tissue sarcomas (STS) such as rhabdomyosarcoma (RMS) and Ewing family of tumors (EFT) have shown that the overall burden of somatic mutations in these tumors is relatively low when compared to most adult tumors. This observation along with recent studies suggest that other features such as chromosomal translocations that appear predominantly in these tumors may play an important role in their biology. Genes resulting from these translocations are known to regulate protein-coding genes that are required for tumor formation. Our studies on these tumors show that these chimeric fusion genes can hijack the cellular machinery that comprises both protein-coding and non-coding networks for tumorigenesis. RESULTS: Gene expression signature of the more aggressive RMS subset that comprises of PAX-FKHR-positive alveolar RMS suggested that the protein-coding NOS1 is most strongly associated and prognostically significant gene in this group. Functional assays confirmed that PAX-FKHR directly regulated its expression. Decreasing NOS1 expression using lentiviral vectors resulted in a decrease in cell survival and reduced tumor growth in vivo. Similar expression analyses comparing EFT, which express the fusion gene EWS-FLI1, with other tumors and normal tissues showed that the non-coding features were more strongly associated with EFT than the coding genes. EWS-FLI1 directly regulates a long intergenic non-coding RNA (lincRNA), FEZF1-AS1. Matrigel assays and tail vein injection models suggested that the lincRNA promotes cell invasion and migration. Chromatin-RNA immunoprecipitation assays revealed interaction of the lincRNA with DNA regions, both coding and non-coding, which are involved in invasion and metastasis. CONCLUSIONS: Fusion genes in pediatric STS activate genomic regions that facilitate tumor pathogenesis by regulating the interactive network between coding and non-coding genes. While fusion-positive RMS are dependent on NOS1 for survival, EFT need lincRNA FEZF1-AS1 for cell migration and tumor propagation. EFT are known to be highly metastatic tumors and our results underscore the complex regulatory networks that are required for cellular migration in these tumors. Understanding the importance of these gene interactions will help development of effective tumor-specific drug therapies that improve treatment while decreasing unwanted side-effects.
Citation Format: Sheetal A. Mitra, Anirban P. Mitra, Jonathan D. Buckley, Timothy J. Triche. Coding and noncoding gene targets in pediatric soft tissue sarcomas. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 597. doi:10.1158/1538-7445.AM2015-597