bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 217: Mutations in iron-sulfur cluster proteins are associated with decreased bladder cancer cell senescence and improved survival outcomes
Authors: Patel Devin , Zheng Fan , Chen Michael , Kreisberg Jason , Silva Erica , Ideker Trey , Licon Kate 
Published: July 2021

Abstract
Recent tumor genome analyses have cataloged hundreds of mutated genes, including a large population of rarely mutated genes with ill-defined roles in cancer. Here we find that, when considering the 10 genes of the iron-sulfur (Fe-S) pathway as an integrated whole, somatic mutations occur with a higher than expected frequency in 21.3% of bladder tumors. Mutations in these genes are associated with increased survival and mutational burden. Analysis of tumor gene expression highlights a relationship between these Fe-S mutations and signalling regulating proliferation and quiescence, with mutations promoting proliferative programs and abolishing maintenance of quiescence. In bladder tumor cells, we show that replication of this proliferative program, using an DYRK1A kinase inhibitor, promotes sensitivity to genotoxic agents. Furthermore, disruption of Fe-S genes ERCC2, MMS19, CIOA1, BRIP1 or POLD1 promotes cell proliferation and concomitant sensitivity to genotoxic agents. These results suggest a model in which Fe-S pathway mutations are selected due to their ability to bypass DNA damage checkpoints and drive proliferation, an aspect which simultaneously creates vulnerability to chemotherapy and resultant improvements in survival.
Citation Format: Devin Patel, Fan Zheng, Michael Chen, Jason Kreisberg, Erica Silva, Trey Ideker, Kate Licon. Mutations in iron-sulfur cluster proteins are associated with decreased bladder cancer cell senescence and improved survival outcomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 217.
Abstract 2184: Gene characteristics of Chinese patients with small bowel cancer
Authors: Zhao Quan , Zhang Hushan , Lei Zhuyun , Sheng Jianing , Xiong Dun 
Published: July 2021

Abstract
Background: Small bowel cancer is a rare malignancy which account for only 1-3% of all malignant gastrointestinal tumors. Herein, we aim to provide an overview of gene characteristics of Chinese patients with small bowel cancer based on the location of the tumor in the small bowel.
Methods: Tumor samples of 324 Chinese patients with small bowel cancer were consecutively collected in China from February 2018 to May 2020, among them, 289 patients with cancer located in duodenum (group 1), 35 patients with cancer located in the other region of small bowel (group 2). Next generation sequencing (NGS) was performed to detect gene mutation, microsatellite instability (MSI), and tumor mutational burden (TMB) measured by a 733 gene panel by 3D Medicines, a laboratory accredited by College of American Pathologists (CAP) and Clinical Laboratory Improvement Amendments (CLIA).
Results: NGS results revealed that the main mutated genes were different between two groups, in detail, the top ten gene mutation in group 1 were TP53 (51.4%,18/35), KRAS (45.7%, 16/35), APC (34.3%, 12/35), POLE (20.0%,7/35), PIK3CA/POLD1/MSH2 (17.1%,6/35), mTOR/PRSS1/LPR1B/BRCA1/SMAD4 (14.3%,5/35). While top ten gene mutation in group 2 were TP53 (66.4%,192/289), KRAS (49.8%, 144/289), ERCC1 (38.8%, 112/289), UGT1A1 (31.5%, 91/289), APC (29.4%, 85/289), BRCA1 (28.7%,83/289), AKT2 (27.3%, 79/289).In addition, TMB level and percentage of MSI-H were also compared between the two groups. 12 patients were available for TMB analysis in group 1, 59 for group 2, the average TMB level in two groups were 23.84 mutants/Mb and 7.8 mutants/Mb, respectively. 50%(6/12) and 11.8%(7/59) were under 10 mutants/Mb in two groups. What's more, the percentage of MSI-H in two groups were 16.7% (5/30) and 3.2% (8/243).
Conclusion: Patients with cancer located in duodenum patients with cancer located in the other region of small bowel displayed obvious difference in gene landscape, this imply that these patients should be treated differently.
Citation Format: Quan Zhao, Hushan Zhang, Zhuyun Lei, Jianing Sheng, Dun Xiong. Gene characteristics of Chinese patients with small bowel cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2184.
Abstract 2192: Transcriptomic classification of renal cancer: a machine learning approach
Authors: Satter Khaled Bin , Tran Paul MH , Purohit Sharad B. , She Jin-Xiong 
Published: July 2021

Abstract
Introduction: Accurate diagnosis is essential for cancer treatment. Sometimes, it is difficult to confirm histological diagnosis due to inadequate tissue sample or preparation. Using molecular markers for classification would be ideal in such cases. For renal cell carcinoma(RCC), we developed a molecular classification based on transcriptomics to address these issues and aid current diagnostic workflow.
Method: We obtained transcriptomic and phenotype data of renal cell carcinoma from The cancer genome atlas (TCGA) data repository. We developed an unsupervised algorithm, Density-based UMAP, based on two clustering methods, UMAP (Uniform manifold approximation and projection) and DBScan (Density-based spatial clustering of applications with noise). We iterated this algorithm 1000 times with random 1000 genes each time and classified each sample in each iteration. We used plurality voting of at least 70% of the iterations for consensus groups. The algorithm was able to identify all the major histological subtypes. We ran a differential expression analysis for each group. Finally, we developed a classification gene signature and a supervised algorithm to classify subtypes with fewer genes and implement this signature in an RCC metanalysis.
Results: Density-based UMAP Algorithm classified the samples with 91.4% concordance with WHO 2016 classification. Among the discrepant cases, 4.4 % cases (46) were not diagnosed the same as their histological classification. 4.2 % (44) cases were shown a mixed expression profile. These cases are of further interest as they might respond better with a different treatment. Based on molecular characteristics they share with major subtypes, they are named ClCh, Clear 2, and Clear 3. ClCh and Clear 2 have shown to be indolent and, Clear 3 has shown to be very aggressive. We manually curated 328 genes for supervised learning from differential expression analysis between the groups and able to identify the groups in a metanalysis.
Conclusion: Transcriptomic profiling is fast, robust and, simple. It can help in diagnosing histologically discrepant cases. This classifier would be a good edition in renal cancer diagnostic workflow and can complement current diagnostic guidelines for renal cancer.
Citation Format: Khaled Bin Satter, Paul MH Tran, Sharad B. Purohit, Jin-Xiong She. Transcriptomic classification of renal cancer: a machine learning approach [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2192.
Abstract 2194: Comparison of molecular profiling between Chinese cholangiocarcinoma and gallbladder cancer through next-generation sequencing
Authors: Yu Chao , Zhang Hushan , Luo Jun , Zhao Songling 
Published: July 2021

Abstract
Background: Recently, some researchers proposed that molecular targeted therapies is ready for “prime time” in biliary tract cancer. However, few large-scale research data specifically analyze and compare the molecular characteristics of biliary tumors in the Chinese population. Here, we aim to report difference of molecular profiling of biliary tract cancers between Chinese cholangiocarcinoma (CCA) and gallbladder cancer (GCC) through next-generation sequencing, and summarize percentage of main targetable genetic alterations for CCA and GBC.
Methods: Totally 1439 tumor sample of Chinese patient with biliary tract cancer were consecutively collected in China from January 2018 to July 2020, 907 patients were CCA, 532 were GCC. Gene mutation, microsatellite instability (MSI) were detected through next generation sequencing (NGS) by 3D Medicines, a laboratory accredited by College of American Pathologists (CAP) and Clinical Laboratory Improvement Amendments (CLIA).
Results: The main mutational gene between CCA and GCC were compared, and results showed that the top ten gene mutation in CCA patients were TP53 (57.6%,522/907), KRAS (35.2%, 320/907), XRCC5 (27.7%, 251/907), CYP2D6 (26.8%,243/907), MDM2 (26.0%,236/907), MSH2 (25.7%,233/907), BLM/VEGFA (24.9%,226/907), POLD (24.7%,224/907), PRSS1 (23.6%,214/907), ATM (23.3%, 212/907). While top ten gene mutation in GCC group were TP53 (76.3%,406/532), MSH2 (43.0%,229/532), CYP2D6 (30.4%, 162/532), MDM2 (28.8%,153/532), VEGFA (27.6%,147/532), POLD1 (27.4%, 146/532), BLM (27.4%,146/532), ATM (25.6%,136/532), PRSS1 (25.2%,134/532), PRKDC (24.8%,132/532). In addition, percentage of the main targetable genetic alterations were also compared between CCA and GCC, such as IDH (5.7% vs 0.9%), FGFR (10.2% vs 10.7%), BRAF (5.1% vs 4.3%), PIK3CA (9.9% vs 14.8%), NTRK (7.4% vs 8.3%), ERBB2/3 (11.8% vs 24.8%), CDKN2A/2B(18.5% vs 23.9%), ARID1A(17.3% vs 17.7&), PTEN (10.3% vs 13.9%), MET (6.3% vs 7.3%), SMAD4 (14.6% vs 14.5%).
Conclusion: Accurately understand the gene mutation characteristics of biliary tract tumors is required to make “Precision Medicine” a reality for the “majority” of patients diagnosed with biliary tract cancer. Chinese patients with CCA and GCC have different gene mutations, especially the proportion of mutant genes that are currently targetable. Therefore, different strategy should be performed for CCA and GCC patients.
Citation Format: Chao Yu, Hushan Zhang, Jun Luo, Songling Zhao. Comparison of molecular profiling between Chinese cholangiocarcinoma and gallbladder cancer through next-generation sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2194.
Abstract 2202: Genetic characterization of metastasis and prognosis in high-grade serous ovarian cancer
Authors: Kotnik Emilee N. , Spies Nicholas C. , Li Tiandao , Inkman Matthew , Zhang Jin , Martins-Rodrigues Fernanda , Hagemann Ian S. , McCourt Carolyn K. , Thaker Premal H. , Hagemann Andrea R. , Powell Matthew A. , Mutch David G. , Maher Christopher A. , Miller Christopher A. , Fuh Katherine C. 
Published: July 2021

Abstract
High-grade serous ovarian cancer (HGSC) is the most lethal histotype of ovarian cancer and is highly prone to metastasis, with the majority of patients presenting at advanced stages of disease. There are few targeted treatment options for HGSC patients, especially for women with high metastatic tumor burdens. In order to identify potential genetic targets in metastatic disease, we characterized the genomic and transcriptomic alterations of metastatic tumors in HGSC patients. In this study, matched normal tissue, primary, and metastatic tumors from 23 HGSC short-term (ST) survivors (overall survival [OS] &lt;3.5 years) and 14 long-term (LT) survivors (OS &gt;5 years) underwent whole exome and RNA sequencing. We compared somatic mutations, copy number alternations, mutational burdens, differential expression, immune cell fractions, and gene fusion predictions between the primary and metastatic tumors of the ST and LT survival groups.
We confirmed that tumors of LT survivors were more likely to have BRCA1 alterations and more copy-altered segments when compared to tumors of ST survivors. There was a higher percentage of shared variants between the primary and metastatic tumors for ST survivors compared to LT survivors. ST survivors also had a greater mutational burden and more predicted gene fusions than LT. We observed few differentially expressed genes between primary and metastatic tumors, but we did observe significant differences between the transcriptomes of LT and ST survivors' tumors. Overall, we observed that HGSC primary and metastatic tumors had similar genomic and transcriptomic landscapes, but we identified genetic characteristics specific to metastatic tumors that correlate with survival.
Citation Format: Emilee N. Kotnik, Nicholas C. Spies, Tiandao Li, Matthew Inkman, Jin Zhang, Fernanda Martins-Rodrigues, Ian S. Hagemann, Carolyn K. McCourt, Premal H. Thaker, Andrea R. Hagemann, Matthew A. Powell, David G. Mutch, Christopher A. Maher, Christopher A. Miller, Katherine C. Fuh. Genetic characterization of metastasis and prognosis in high-grade serous ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2202.
Abstract 2207: Genomic associations of biological sex and survival in head and neck squamous cell carcinoma
Authors: Yao Alexandria G. , Mezghani Nadia , Taylor Alison M. , Momen-Heravi Fatemeh 
Published: July 2021

Abstract
Approximately half of all head and neck squamous cell carcinoma patients die within five years of diagnosis despite treatment. Recent studies revealed that females have a worse overall prognosis; however, the genetic and molecular underpinnings have not yet been identified. We investigated the genetic characteristics of head and neck squamous cell carcinomas stratified by HPV status and biological sex. Within the HPV-negative cohort, female patients have worse survival outcomes compared to male patients, although tumors in female patients show lower levels of aneuploidy alterations and copy number changes. Specifically, chromosomes 4, 5, 6, and 20 were amplified at higher frequency in the tumors of male patients compared to female patients. Analysis of mRNA expression found that genes most highly expressed in females compared to males included sex-chromosome genes XIST and TISX. Interestingly, along with y chromosome gene PRKY, Notch signaling gene HES7 was also up-regulated in the tumors of male patients. In addition, tumors of female patients showed higher expression of immune pathway genes, even when potential confounding factors of age and tumor location are considered. This study provides new insight into possible gene expression biomarkers for HNSCC in female patients. Future research will incorporate these findings to better assess therapeutic response in women with HNSCC.
Citation Format: Alexandria G. Yao, Nadia Mezghani, Alison M. Taylor, Fatemeh Momen-Heravi. Genomic associations of biological sex and survival in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2207.
Abstract 2219: Analysis of gene landscape of small cell lung cancer of Chinese through next-generation sequencing
Authors: Zhang Jing , Zhang Hushan , Ling Feng , Wang Yuanhan , Li Long , Yang Song 
Published: July 2021

Abstract
Background: As the more malignant subtype of lung cancer, small cell lung cancer (SCLC) displayed more aggressive and worse prognosis. Standard treatments have rarely changed in decades, therefore, in recent years, there have been attempts to explore targeted therapy and even immunotherapy. However, SCLC has more challenging targets. It was reported that almost 100% of SCLC has p53 and Rb mutations, and also has functional changes in Myc. Here we report some data about gene mutation of SCLC of Chinese patients.
Methods: Tumor samples of 410 SCLC patients were consecutively collected in China from July 2018 to May 2020, next generation sequencing (NGS) was performed to detect gene mutation, and tumor mutational burden (TMB) measured by a 733 gene panel. PD-L1 expression detected by using Dako PD-L1 IHC 22C3 pharmDx, Tumor Proportion Score (TPS) was used to determine expression of PD-L1. TPS was arranged into the following intervals: strong positive ≥50%, moderate positive ≥5% and &lt;50%, weak positive ≥1% and &lt;5%, and negative &lt;1%. All these were performed by 3D Medicines, a laboratory accredited by College of American Pathologists (CAP) and Clinical Laboratory Improvement Amendments (CLIA).
Results: NGS results showed that the top gene mutation in these 410 Chinese SCLC patients were TP53 (88.0%,361/410), RB1(63.9%,262/410), BRCA1/2(34.0%,139/410), LRP1B(28.3%,116/410), FAM135B(24.1%,99/410), PIK3CA(23.9%,98/410), CYP2D6(21.0%,86/410), POLA1(20.2%,83/410), NTRK1(19.5%,80/410), MSH2(19.3%,79/410), ATM(19.3%,79/410), AKT2(18.8%,77/410), VEGFA(18.8%,77/410). Furthermore, 159 samples available for TMB analysis, and results showed that the average TMB level was 11.7 mutants/Mb, and 49.7%(79/159) were higher than 10 mutants/Mb, and 50.3%(80/159) were under 10mutants/Mb. In addition, 167 samples available for PD-L1 analysis, and results showed that 86.8% (145/167) with PD-L1 negative, 7.8(13/167) moderate positive, none with PD-L1 strong positive.
Conclusion: Chinese patients with SCLC have rich spectrum of gene mutations, it suggests that targeted therapy should also have certain potential. In addition, about half of SCLCs have a TMB level above 10mutants/Mb, and immunotherapy should been considered more in the future treatment for Chinese SCLC patients.
Citation Format: Jing Zhang, Hushan Zhang, Feng Ling, Yuanhan Wang, Long Li, Song Yang. Analysis of gene landscape of small cell lung cancer of Chinese through next-generation sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2219.
Abstract 2254: Coding and noncoding RNA determinants of invasion and migration in papillary thyroid cancer
Authors: Carnazza Michelle , Dadafarin Sina , Moscatello Augustine , Tiwari Raj , Geliebter Jan 
Published: July 2021

Abstract
Papillary thyroid cancer (PTC) is now the 8th most common cancer in women in the United States and has been increasing in incidence over the last few decades. While it is often curable, aggressive forms of PTC that are not adequately treated by current therapeutic modalities invade into surrounding tissue, with a poor prognosis. Thus, the identification of genes involved in PTC migration and invasion is an unmet need. Differentially expressed (PTC vs. matched, normal) coding and noncoding genes from our own biobank were ranked, comparing invasive vs noninvasive, and lymph node positive vs lymph node negative samples. This analysis was supplemented with the interrogation s of The Cancer Genome Atlas (TCGA) PTC gene expression database for survival-associated genes (Kaplan Meier survival curves) utilizing the Xena Browser. This meta-analysis identified genes with a significant impact on survival, that correlated with lymph node metastasis and tumor invasion. SPOCK3, a Ca+2-binding proteoglycan protein with metalloendopeptidase activity, with a role in both extracellular matrix (ECM) degradation and ERK signaling, correlated with both invasiveness and lymph node spread. SLC30A3 (Solute Carrier Family 30 Member 3), involved in the accumulation of zinc in synaptic vesicles and the transport of sugars, bile salts, organic acids, metal ions and amine compounds, also correlated with both invasiveness and lymph node spread. COL26A1, was found to be correlated to tumor invasion and codes for collagen type XXVI α1 chain with known roles in degradation of the ECM and collagen chain trimerization. Long noncoding RNAs (lncRNAs) have vast implications in different cancer types with roles in gene expression via modulation of coding and noncoding RNAs, and are cell, tissue and stage-specific. lncRNAs were identified that correlated with differentiation, invasion and lymph node spread. CRISPR guides were designed and introduced into thyroid cancer cell lines and decreased the invasion and migration capacity of the thyroid cancer cells. This implies their potential use as prognostic markers and actionable therapeutic targets for small molecule inhibitors.
Citation Format: Michelle Carnazza, Sina Dadafarin, Augustine Moscatello, Raj Tiwari, Jan Geliebter. Coding and noncoding RNA determinants of invasion and migration in papillary thyroid cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2254.
Abstract 2257: Effect ofALDH1L1folate enzyme on hepatocellular carcinoma inachemical carcinogenesismodel
Authors: Sharma Jaspreet , Krupenko Natalia I. , Pediaditakis Peter , Helke Kristi , Strickland Kyle C. , Krupenko Sergey A. 
Published: July 2021

Abstract
Background: ALDH1L1 (aldehyde dehydrogenase 1 family member L1, or cytosolic 10-formyltetrahydrofolate dehydrogenase) is an abundant enzyme in folate metabolism representing about 1% of total soluble protein in hepatocytes. Expression of this protein is strongly and ubiquitously downregulated in human cancers through the promoter methylation. Several studies indicate that patients with hepatocellular carcinoma who had low expression of ALDH1L1 had poorer prognosis than those with high expression.
Hypothesis: We propose that in the absence of ALDH1L1, liver tumors proliferate faster and grow to a larger size.
Methods: The effect of the Aldh1l1 knockout (Aldh1l1−/−) on hepatocellular carcinoma was investigated using DEN (diethyl nitrosamine) model of chemical carcinogenesis. Fifteen-days-old male Aldh1l1−/- mice and their wild-type littermate controls (Aldh1l1+/+) were injected intraperitoneally with DEN at the dose of 15 mg/kg body weight. Mice were sacrificed 10, 20, 28- and 36-weeks post-injection and livers were examined for for histopathology.
Results: Significant reduction in total body weight was observed in the DEN-injected knockout compared to wild type animals at 28 and 36 weeks. Immunohistochemical analysis reveals that tumor size was significantly bigger in Aldh1l1−/− compared to Aldh1l1+/+ mice and also indicated fibrosis in livers of knockout vs wild-type mice. Vascular involvement, highlighted by reticulin staining, was present in both Aldh1l1−/− and Aldh1l1+/+ mice as early as 20 weeks after the injection. Tumor multiplicity did not differ significantly between the Aldh1l1−/− and Aldh1l1+/+ animals.
Conclusion:. Aldh1l1 knockout promoted aggressiveness of liver tumors without affecting the tumor initiation.
Acknowledgement: These studies were supported by the National Institutes of Health grants DK54388 and CA095030 (S.A.K.).
Citation Format: Jaspreet Sharma, Natalia I. Krupenko, Peter Pediaditakis, Kristi Helke, Kyle C. Strickland, Sergey A. Krupenko. Effect ofALDH1L1folate enzyme on hepatocellular carcinoma inachemical carcinogenesismodel [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2257.