bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4574: Genomic copy number variations characterize prognosis of oropharyngeal squamous cell carcinoma, including p16 positive subset, after surgery-based treatment
Authors: Jung Yuh-S. , Rhie Arang , Kim Jong-Il , Lee Jin Soo , Ryu Junsun , Park Weon Seo 
Published: August 2015

Abstract
Background High-risk human papillomavirus (HPV)-related (+) oropharyngeal squamous cell carcinoma (OSCC) exhibits unique clinical and molecular characteristics, compared to HPV-unrelated - OSCCs. As different patterns of genomic instability is expected in HPV-driven carcinogenesis, we questioned if patterns of genomic copy number variations (CNVs) differ depending on HPV association, and predict prognosis, after surgery-based treatment for OSCCs in Korean population. Methods Fifty-eight OSCCs patients, who underwent surgery-based treatment and followed for 42 months on median, were enrolled. HPV status was determined by p16 immunohistochemistry (IHC), and HPV DNA PCR. Genome-wide CNV analysis was performed using array-based comparative genomic hybridization of genomic DNA from paraffin-embedded specimen. Clinical association and survival analyses were followed. Results p16 predicted the overall survival (HR = 0.27, CI: 0.39-0.80, p = 0.0006), better than HPV DNA PCR (HR = 0.83, CI: 0.66-1.29, p = 0.64) or smoking history (HR = 2.18, CI: 0.92-5.18, p = 0.071). In overall, number of CNVs did not significantly differed between p16+/- groups. However, 30 locus showed different CNV pattern between these groups. PRDM2 was amplified only in p16+ group, while EGFR and 11q13.3 was more amplified in p16- patients. Loss of FGF18 lead to worse prognosis, and gain of CDK10 and RAD18 was linked to better prognosis in all patients. Amplification of HRAS and loss of KDR lead to better OS in p16+ group. Conclusions After surgery-based treatment, p16+ OSCCs exhibits different CNV patterns at some loci, compared with p16- counterpart. Specific patterns of CNVs do predict better survival, especially in p16+ OSCCs. In the future, clinical trials should stratify patients based on these patterns to apply escalated treatment to obtain better survival.
Citation Format: Yuh-S. Jung, Arang Rhie, Jong-Il Kim, Jin Soo Lee, Junsun Ryu, Weon Seo Park. Genomic copy number variations characterize prognosis of oropharyngeal squamous cell carcinoma, including p16 positive subset, after surgery-based treatment. [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 4574. doi:10.1158/1538-7445.AM2015-4574
Abstract 4586: Association of FUT2 gene variant, gut bacteria and colorectal adenomas
Authors: Okunola Winifred , McCoy Amber , Dulal Santosh , Keku Temitope O. 
Published: August 2015

Abstract
The fucosyltransferase 2 (FUT2) gene is responsible for the expression of the ABO blood group antigens. These antigens serve as anchors for a variety of microbes in the gut and may confer increased susceptibility to microbial infections and diseases. We assessed the association between a genetic variant in the FUT2 gene (rs516246) and mucosal-adherent gut bacteria in relation to colorectal adenomas. Genomic DNA from 200 consented screening colonoscopy subjects was genotyped for FUT2 rs516246 using a TaqMan genotyping assay. qPCR was performed to target the 16S rRNA gene for specific bacteria. Statistical analysis included t-test, logistic regression Chi-squared tests and Spearman's correlation test. Results show that, except for age and waist-hip ratio, patient characteristics were similar for cases and controls. Higher abundance of E. coli and Eubacteria was associated with adenoma status. There was a null association between FUT2 genotype and adenomas. Similarly, gut bacteria and adenoma status was not strongly influenced by FUT2 genotype. In conclusion: the FUT2 (rs516246) gene variant does not appear to influence the relationship between gut bacteria and colorectal adenomas.
Citation Format: Winifred Okunola, Amber McCoy, Santosh Dulal, Temitope O. Keku. Association of FUT2 gene variant, gut bacteria and colorectal adenomas. [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 4586. doi:10.1158/1538-7445.AM2015-4586
Abstract 4588: Whole genome hypo- and hyper-methylation sequencing among Africa American patients with colorectal cancer
Authors: Ashktorab Hassan , Shakoori Afnan , Zarnogi Shatha , Sun Xueguang , Varma Sudhir , Lee Edward , Shokrani Babak , Laiyemo Adeinko O. , Washington Kareem , Brim Hassan 
Published: August 2015

Abstract
Background: Colorectal cancer (CRC) involves epigenetic changes including DNA hypomethylation, a paradigm shift in the role of DNA methylation alterations in colorectal carcinogenesis.
Aim: Here we performed Reduced Representation Bisulfite Sequencing (RRBS) on a normal, and a tumor patient's tissue DNA to elucidate hyper- and hypomethylaed target genes in colorectal cancer progression in this population.
Methods: Genomic DNA was isolated from fresh frozen surgical tissues from a patient with normal colon, and from a carcinoma patient. RRBS was performed on these DNA samples for hyper- and hypomethylation targets identification. Alignment, mapping and CpG methylation analyses were performed. Preferential hypomethylated pathways were determined using Ingenuity Pathway Analysis (IPA).
Results: We identified the hyper (6360 CpG sites) and hypo-methylation (4845 CpG sites) status of top genes in the CpG Island within promoter regions (19 and 18 genes respectively). Top hyper- and hypomethylated CpG Island outside promoter regions (16 and 18 genes, respectively) were also identified. Among these top genes, CDH4 and SOX21 were reported to be hypermethylated in CRC and SCUBE2 (112 methylated CpG) mapped by IPA to the Hedgehog, TGF-β, and VEGF Signaling pathways was reported to play a role in breast cancer. Among the top hypomethylated genes, ACOT9 (97 CpGI sites) and RIN2 (40 CpGI sites) might play a significant role in CRC in AAs, since IPA mapped these markers to the Wnt/β-catenin, VEGF and PTEN signaling pathways. ACOT9 was found to play a role in breast cancer.
Conclusion: This work provides insight into differential CpG island hyper- and hypo-methylation profiles in CRC and provides a window into the more complex epigenetic events associated with CRC, including the hypomethylation of known and novel genes. Investigations into the possible roles of the novel gene targets in the context of early and prognostic methylation biomarkers are underway.
Citation Format: Hassan Ashktorab, Afnan Shakoori, Shatha Zarnogi, Xueguang Sun, Sudhir Varma, Edward Lee, Babak Shokrani, Adeinko O. Laiyemo, Kareem Washington, Hassan Brim. Whole genome hypo- and hyper-methylation sequencing among Africa American patients with colorectal 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 4588. doi:10.1158/1538-7445.AM2015-4588
Abstract 4613: MDM4 SNP 34091 (rs4245739) effect on risk of breast, colon, lung, prostate, endometrial and ovarian cancer
Authors: Gansmo Liv B. , Bjørnslett Merete , Dørum Anne , Salvesen Helga , Romundstad Pål , Hveem Kristian , Vatten Lars , Lønning Per Eystein , Knappskog Stian 
Published: August 2015

Abstract
Background
MDM4 enhances MDM2's E3 ligase activity causing ubiquitin-proteasome-dependent degradation of p53. Thus, elevated levels of both MDM4 and MDM2 may result in p53 inactivation and elevated cancer risk. A single nucleotide polymorphism in the MDM4 3′ UTR (SNP34091A&gt;C; rs4245739) has been found to exert biological function as the SNP34091C allele creates a putative target site for hsa-miR-191 leading to specific hsa-miR-191 down-regulation of MDM4. Further, the SNP34091AA genotype is associated with increased risk for both recurrence and tumor related death in estrogen negative ovarian cancer patients. In the present study we assessed the potential effect of MDM4 SNP34091A&gt;C on cancer risk in six major cancer forms.
Materials and methods
We analyzed 1717 breast-, 1331 lung-, 1531 colon-, 2501 prostate cancer cases and 3747 healthy controls form the same population based study (CONOR) as well as 1404 endometrial- and 1699 ovarian cancer cases from hospital based studies.
All samples were genotyped for MDM4 SNP34091A&gt;C using custom Light-SNiP assay on a LightCycler 480 II instrument. Potential associations between MDM4 SNP34091 and cancer risk were estimated by calculating Odds Ratio (OR) with 95% confidence intervals (CI). All statistical analyses were performed using the IBM SPSS 19 software.
Results
We observed no significant association between MDM4 SNP34091A&gt;C status and cancer risk in any of the analyzed cancer forms. Interestingly, stratifying the ovarian cancer samples according to grade and histology, we observed a reduced risk of high grade serous ovarian cancer in patients harboring the MDM4 SNP34091AA genotype (OR = 0.80; 95% CI = 0.65 - 0.98). Stratifying according to MDM2 SNP309 status we found the MDM4 SNP34091A allele to be associated with increased risk for breast cancer (OR = 2.10; 95% CI = 1.08 - 4.10) in patients carrying the SNP309 GG genotype.
Conclusions
The data presented here indicate that the effect of MDM4 SNP34091 on cancer risk may be tissue specific and that there may be cooperative effects with MDM2 SNP309.
Citation Format: Liv B. Gansmo, Merete Bjørnslett, Anne Dørum, Helga Salvesen, Pål Romundstad, Kristian Hveem, Lars Vatten, Per Eystein Lønning, Stian Knappskog. MDM4 SNP 34091 (rs4245739) effect on risk of breast, colon, lung, prostate, endometrial and ovarian 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 4613. doi:10.1158/1538-7445.AM2015-4613
Abstract 4621: Validation and calibration of next-generation sequencing to identify Epstein-Barr Virus-positive gastric cancer
Authors: Camargo M. Constanza , Bowlby Reanne , Chu Andy , Pedamallu Chandra S. , Thorsson Vesteinn , Elmore Sandra , Mungall Andrew , Bass Adam , Gulley Margaret L. , Rabkin Charles S. 
Published: August 2015

Abstract
Background: Gastric adenocarcinoma was recently classified by a large genomic study into four molecular subtypes, including one defined by Epstein-Barr virus (EBV)-positivity. EBV infection in tumors is conventionally assessed by in situ hybridization (ISH), but detection of viral nucleic acids by next-generation sequencing represents a potential alternative.
Methods: Normalized EBV read counts were determined by whole genome, whole exome, mRNA and miRNA sequencing for 295 fresh-frozen gastric tumor samples. Formalin-fixed, paraffin-embedded tissue sections were retrieved for ISH confirmation of 13 high-EBV and 11 low-EBV cases selected at random.
Results: By each sequencing method, numbers of EBV reads were bimodally distributed across tumors, with a minority having much higher counts. In pairwise comparisons, individual samples were either consistently high or consistently low by all genomic methods for which data were available. Empiric cut-offs based on molecular data of 1000 normalized reads for whole genome, 100 for exome, 4 for mRNA and 5000 for miRNA had perfect concordance identifying 26 (9%) tumors as EBV-positive. One sample tested by ISH lacked tumor cells. For the 23 tumors with EBV status determined by both approaches, EBV-positivity or -negativity by molecular testing was confirmed by EBER-ISH in all but one case (kappa = 0.91). The exception was a microsatellite instability-type cancer EBV-negative by both mRNA and miRNA sequencing, with equivocally positive ISH interpretation.
Conclusions: EBV-positive gastric tumors may be accurately identified by quantifying viral sequences in genomic data. Simultaneous analyses of human and viral DNA, mRNA and miRNA could streamline tumor profiling for clinical care and research.
Citation Format: M. Constanza Camargo, Reanne Bowlby, Andy Chu, Chandra S. Pedamallu, Vesteinn Thorsson, Sandra Elmore, Andrew Mungall, Adam Bass, Margaret L. Gulley, Charles S. Rabkin. Validation and calibration of next-generation sequencing to identify Epstein-Barr Virus-positive gastric 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 4621. doi:10.1158/1538-7445.AM2015-4621
Abstract 4628: Analysis of melanoma GWAS data suggests specific risk loci influencing age of onset of melanoma
Authors: Cymerman Rachel M. , Bigio Benedetta , Seybold Martin P. , Polsky David , Wittkowski Knut M. 
Published: August 2015

Abstract
Introduction/Purpose: The average age of diagnosis of melanoma is younger than that of other major cancers. In addition, melanoma is the second most common cancer among individuals in their 20s. Analyzing GWAS data by ‘wide-locus region’ (i.e. analyzing multiple nearby single nucleotide polymorphisms (SNPs) together) increases statistical power compared to single-SNP analyses. This approach has uncovered new associations in GWAS data for diseases other than melanoma. By applying wide-locus analysis to GWAS data from melanoma cases, we aimed to discover common genetic risk variants related to age of melanoma onset.
Procedures: We re-analyzed data from the 1977 melanoma cases of European ancestry made available by the MD Anderson Cancer Center study (accession: phs000187.v1.p1). Patients were genotyped on the Illumina OMNI1-Quad chip. Biostatistical analysis was performed from a window moving across the whole genome using u-statistics for multivariate, genetically structured wide-locus data to derive genetic risk scores to determine if any gene regions were associated with age of onset in melanoma patients. This statistical approach resulted in a genome-wide significance level of p&lt;10−5.64.
Results: Common variants in several genes were associated with melanoma age-of-onset at the level of genome-wide significance. The most significant functional risk loci were located at DLEU1 (p&lt;10−6.75), NRP1 (p&lt;10−6.66), PTPN11P (p&lt;10−6.49) and BAT1/ATP6/NFKBIL (p&lt;10−6.41). Of note, none of these risk loci have been shown to be associated with risk of developing melanoma overall, or longevity in prior GWAS. The NRP1 and PTPN11P genes have been linked to the RAS pathway, an important driver of melanoma pathogenesis.
Conclusions: Our analysis revealed novel associations between several common genetic variants and earlier age of melanoma diagnosis. Some of these loci interact with the RAS pathway. Additional studies of common genetic variants and age of cancer diagnosis using this approach may reveal similar findings in other melanoma cohorts and possibly other cancer types.
Citation Format: Rachel M. Cymerman, Benedetta Bigio, Martin P. Seybold, David Polsky, Knut M. Wittkowski. Analysis of melanoma GWAS data suggests specific risk loci influencing age of onset of melanoma. [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 4628. doi:10.1158/1538-7445.AM2015-4628
Abstract 463: Successful generation of tumor infiltrating lymphocytes from human non-small cell lung cancer specimens
Authors: Kim Kyoung-Hee , Kargl Julia , Lee Sylvia , Houghton McGarry 
Published: August 2015

Abstract
Tumor infiltrating lymphocytes (TILs) are naturally occurring cancer-fighting T cells found within malignant tumors. After decades of research, patient-derived TIL populations have been successfully re-infused into melanoma subjects, and have produced impressive treatment effects in a subset of cases. To date, the successful generation and usage of TIL populations for non-small cell lung cancer (NSCLC) patients has not been reported. Generating TILs from NSCLC tissue presents several challenges, as immune cell populations residing within the lungs are constantly exposed to numerous inhaled antigens and other particulate matter.
Here, we report the successful generation of TILs from three NSCLC specimens from subjects undergoing surgical resection for curative intent. Six distinct lung cancer tissue fragments were cultured in the presence of IL-2 for each of the three cases. Each fragment yielded a TIL population, although their proliferative rates differed substantially. Each TIL population was subjected to flow cytometry to identify the cellular subtypes, and these results were compared to the lymphocyte subset content measured in the original in vivo tumor specimen. Preliminary findings suggest that the ability to generate CD8+ enriched TILs is dependent upon the CD8+ content present in vivo. Low CD8+ content was associated with an abundance of either Tregs or NK cells. Greater than 70% of the CD8+ populations generated displayed an effector phenotype (CCR7-CD45RA+), regardless of the overall cellular composition of the specimen. However, these cells displayed heterogeneous levels of exhaustion markers (PD1, Tim3), which inversely correlated with proliferative rates.
Our results show that TIL populations can be successfully generated from primary human NSCLC specimens. Although the relative cellular content differed for each tissue fragment, we were able to generate at least one CD8+ effector population with low levels of exhaustion for each case. In vitro and in vivo studies to determine the tumor killing capacity of these TIL populations are currently underway.
Note: This abstract was not presented at the meeting.
Citation Format: Kyoung-Hee Kim, Julia Kargl, Sylvia Lee, McGarry Houghton. Successful generation of tumor infiltrating lymphocytes from human non-small cell lung cancer specimens. [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 463. doi:10.1158/1538-7445.AM2015-463
Abstract 4630: Heterogeneity revealed through meta-analysis might link geographical differences with nasopharyngeal carcinoma incidence in Han Chinese
Authors: Su Wen-Hui , Chiu Chi-Cking , Shugart Yin Yao 
Published: August 2015

Abstract
Nasopharyngeal carcinoma (NPC) is an epithelial malignancy highly prevalent in Southern China with varying incidence rates among Han Chinese in different geographic regions. Recently, three independent genome-wide association studies (GWAS) confirmed that the HLA-A was the main risk gene of NPC. However, studies from regions with different incidence rates led to contradictory claims regarding whether HLA-A was the sole risk gene and the association of rs29232 was independent from the HLA-A effect in chromosome 6p21.3 region. To explore whether the differences were caused by genetic factors underlying the varying incidence rates by region in NPC incidence, we performed a meta-analysis by selecting 5 single-nucleotide polymorphisms (SNPs) in chromosome 6p21.3 from 3 published GWAS studies and 3 published case-control studies from Southern China (Taiwan, Guangdong and Guangxi) involving 7 828 NPC patients and 8 813 healthy controls from Han Chinese. The rs29232 SNP exhibited a moderate level of heterogeneity (I2 = 43%) that disappeared (I2 = 0% and 4%) after stratifying the studies according to moderate- and high-incidence NPC regions. The estimated odds ratio (OR) of rs29232 (OR: 1.70, 95% confidence interval [CI]: 1.47-1.95) was higher in the moderate-incidence region than in the high-incidence region (OR: 1.42, 95% CI: 1.30-1.56). The heterogeneity revealed by meta-analysis of rs29232 might be associated with differences in NPC incidence in Han Chinese between geographic regions. Therefore, we postulate that moderate heterogeneity in rs29232 might contribute to the varying incidence rates between regions due to a genetic cause in NPC incidence. The higher OR of rs29232 and the fact that it was independent of the HLA-A effect in the moderate-incidence population suggested that rs29232 might have greater relevance to NPC in a moderate-incidence population than to a high-incidence population. To our knowledge, this is the first study to demonstrate that genetic factors might involve in the varying disease incidence rates by region. This further suggests that the disease incidence rate should be considered as a potential confounding factor when conducting large, cross-region meta-analysis in NPC.
Citation Format: Wen-Hui Su, Chi-Cking Chiu, Yin Yao Shugart. Heterogeneity revealed through meta-analysis might link geographical differences with nasopharyngeal carcinoma incidence in Han Chinese. [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 4630. doi:10.1158/1538-7445.AM2015-4630
Abstract 4632: Poor survival associated with NUAK1 overexpression in serous ovarian cancer may be explained by chemotherapy resistance
Authors: Phippen Neil T. , Bateman Nicholas W. , Wang Guisong , Hamilton Chad A. , Maxwell George L. , Darcy Kathleen M. , Conrads Thomas P. 
Published: August 2015

Abstract
Objectives: The purpose of this study was to identify and validate novel gene transcripts associated with poor prognosis ovarian cancer.
Methods: Clinical, pathologic, outcomes and transcriptomics data for 22,277 probesets were downloaded for each of 1,183 eligible patients representing six datasets. Cohorts 1 (n = 638) and 2 (n = 545) were used for discovery and validation, respectively. Associations with survival were evaluated using univariate Cox modeling with Wald test and Kaplan-Meier method with log rank test. Odds ratios were evaluated using the Mantel-Haenszel test. NUAK1 expression in ovarian cancer cell lines was examined using immunoblotting.
Results: There were 293 (1.3%) probesets whose expression was associated with survival in serous ovarian cancer patients in cohort 1 that passed false discovery correction, and 19 of these, including NUAK1, validated in cohort 2 (q&lt;0.05). Women with high versus low transcript expression of NUAK1 had worse survival (hazard ratio = 1.4, 95% confidence interval = 1.2-1.64) and increased odds of being diagnosed at advanced age with late stage disease in addition to experiencing suboptimal debulking and earlier disease progression. Higher levels of NUAK1 protein were observed in a panel of chemoresistant versus chemosensitive ovarian cancer cells lines.
Conclusions: Overexpression of NUAK1, also known as AMPK-related protein kinase 5 (ARK5) and a survival factor in nutrient starved cells with low oxygen tension, was identified and validated to predict poor prognosis in a cohort of 1,183 serous ovarian cancer patients, and to be associated with chemoresistance using in vitro models of platinum and taxane resistance in human ovarian cancer.
Citation Format: Neil T. Phippen, Nicholas W. Bateman, Guisong Wang, Chad A. Hamilton, George L. Maxwell, Kathleen M. Darcy, Thomas P. Conrads. Poor survival associated with NUAK1 overexpression in serous ovarian cancer may be explained by chemotherapy resistance. [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 4632. doi:10.1158/1538-7445.AM2015-4632