bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3616: Somatic mutation profiling of colorectal cancer by targeted next generation sequencing
Authors: El-Din Youssef Amira Salah , Moustafa Ahmed , Touny Ahmed Osama , Hassan Zeinab K. , Eldin Mohammed Mohey , Lotfy Mai M. , Nassar Auhood , sayed ola , Zekri Abdel-Rahman N. 
Published: September 2020

Abstract
Aim: This study aimed to sequence custom 96 genes of tumor suppressor genes and oncogenes frequently associated with colorectal cancer (CRC) to identify the frequency of the detected genetic mutations in the disease progression of CRC patients and to develop personalized therapy in those somatic mutation carriers.
Material and methods: Biopsy samples were collected from Egyptian patients classified into inflammatory bowel disease (IBD) (n=20), colonic polyp (CP) (n=38) and CRC (n=60) patients as well as subjects with chronic non-specific colitis served as a control group (n=20). The libraries were performed using Qiaseq UMI-based targeted panel and sequenced via Ion proton sequencer. The detected genetic variants with an average coverage of 500x were annotated against Cosmic and dbSNP and Clinvar databases.
Results: Analysis revealed that 52 genes harbor 128, 47 genes harbor 111, 40 genes harbor 71 and 39 genes harbor 66 somatic variants were detected in the CRC, CP, IBD and control groups; respectively. ARID1A (c.5548dupG (5%)), ATM (c.2572T&gt;C (10%)), AXIN2 (c.1975C&gt;T (5%)), FLCN (c.1285dupC (8%)), KRAS (c.35G&gt;T (8%)), MSH6 (c.3261dupC (5%)), SLC9A9 (c.1765A&gt;G (10%)), TP53 (c.1024C&gt;T (5%)) were found to be the highly frequently detected pathogenic CRC specific variants. We also identified 29 genes harbor 43 common variants. The highly frequently common detected variants were ACVR2A (c.1310delA), ATM (c.5557G&gt;A), BRCA1 (c.3548A&gt;G, c.2612C&gt;T), BRCA2 (c.1114A&gt;C), IGF2 (c.677delG), KIT (c.1621A&gt;C), MLH1 (c.655A&gt;G), MLK4 (c.2223G&gt;T, c.2182G&gt;A), PIK3CA (c.1173A&gt;G), PTPN12 (c.964G&gt;A), RET (c.2071G&gt;A), TP53 (c.121delG, c.215C&gt;G)
Conclusion: Our data showed that our Egyptian genetic makeup is different from other population. Also, the identified somatic mutations are crucial for understanding cancer predisposition and developing personalized therapies for the Egyptian colorectal cancer patients.
Citation Format: Amira Salah El-Din Youssef, Ahmed Moustafa, Ahmed Osama Touny, Zeinab K. Hassan, Mohammed Mohey Eldin, Mai M. Lotfy, Auhood Nassar, ola sayed, Abdel-Rahman N. Zekri. Somatic mutation profiling of colorectal cancer by targeted next generation sequencing [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3616.
Abstract 3628: Multiregional sequencing reveals the heterogeneity and underlying complex evolutionary history in liver cancer metastasis
Authors: Sun Yun-Fan , Wu Pin , Wang Ze-Jian , Song Min-Fang , Zhou Kai-Qian , Zhang Li-Ye , Peng David P. , Fan Jia 
Published: September 2020

Abstract
Cancer metastasis is still the major cause of death, and poorly understood mechanistically. Therefore, increasing number of studies begins to study the genetic profiles of metastatic samples. However, studies from different tumor types show contradicting conclusions on evolution pattern. In this study, we focus on metastasis in hepatocellular carcinoma (HCC). We analyzed 92 primary and their matched 177 metastatic samples from a cohort of 64 HCC patients encompassing 10 distinct metastatic sites. To study the heterogeneity, we generated multi-regional exome and RNA sequencing for both primary and metastatic tumors. The inferred phylogenies showed both monoclonal (48 %) and polyclonal (52%) metastasis. The polyclonal metastasis is further divided into two subgroups: single branch-multiple waves and multiple-branch metastasis, while the majority of polyclonal evolution is derived from single branch-multiple waves metastasis (12 out of 13). In addition, we observed similar frequency of early, intermediate and late dissemination for tumor metastasis. Therefore, both the clonal and temporal heterogeneity lead to the genetic diversity in metastasis of HCC, which results in the inconsistency in driver (potentially targetable) mutations between primary and metastatic tumor samples for over 60% of patients in our cohort. To identify the potential driver genes for metastasis, we included another two cohorts including no-relapse/metastasis (n=32) and intrahepatic relapse (n=42) as a control. However, similar to published datasets, only TP53 showed a significant increase of frequency in metastatic cohort compared with other cohorts. To conclude, to our knowledge, we provided by far the largest metastatic HCC cohort of multi-regional sequencing and revealed the complex evolutionary history of HCC metastasis regarding to the clonal and temporal composition. We speculate that huge heterogeneity in HCC, especially in metastatic tumors, may be the main reason for frequent failure in targeted therapy in HCC.
Citation Format: Yun-Fan Sun, Pin Wu, Ze-Jian Wang, Min-Fang Song, Kai-Qian Zhou, Li-Ye Zhang, David P. Peng, Jia Fan. Multiregional sequencing reveals the heterogeneity and underlying complex evolutionary history in liver cancer metastasis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3628.
Abstract 3643: HDAC6 modulates colon cancer cell migration and invasion
Authors: Li Hui 
Published: September 2020

Abstract
Introduction: Non-histone protein acetylation in cancer cell regulates diverse biological functions that have been associated with tumorigenesis and cancer progression. HDAC6 is a tubulin-specific deacetylase which regulates microtubule-dependent cell movement. Here we investigated the role of HDAC6 on colon cancer progression.
Methods: Colon tumor tissues were analyzed by immunohistochemistry to measure the expression of HDAC6. Attenuation of HDAC6 function was achieved using either inhibitors (Tubastatin and ACY-738) or siRNAs. Cell migration and invasion were determined using transwell assays. CCK8 and flow cytometry were used to assess the cell proliferation and cell survival respectively. We performed quantitative proteomic analyses to monitor changes in the abundance of protein lysine acetylation in response to HDAC6 deficiency. Immunoprecipitation assay was used to determine protein acetylation level and protein-protein interaction.
Results: We identified that HDAC6 was highly expressed in metastatic colon cancer than non-metastatic colon cancer, indicating that HDAC6 is related with tumor metastasis. Selective suppression of HDAC6 or knocking down of HDAC6 significantly decreased colon cancer cell migration and invasion ability in vitro, without affecting cell proliferation and cell survival. In order to further clarify the role of HDAC6 in cell motility, we employed mass spectrometry-based label-free quantitative proteomics using human colon cancer cell line. We identified 42 proteins with &gt; 2-fold increase of the acetylation level in the absence of HDAC6. These proteins are significantly enriched in processes related to cell-cell adhesion, cell division and several signaling pathways including cAMP and FoxO signaling pathway. We selected ENAH, an actin associated protein, as a potential new substrate of HDAC6, which has been previously reported to play important roles in cytoskeleton remodeling and cell polarity establishment. Immunoprecipitation analysis showed that HDAC6 can associate with ENAH under physical conditions. Besides, ENAH showed elevated acetylation in response to HDAC6 deletion.
Conclusions: Our findings showed that inhibition of HDAC6 decreased the colon cancer cell migration and metastasis probably through regulating the acetylation level of ENAH. Our study also provided a resource of putative cytoplasmic targets of this deacetylase for further investigation. Considering that small molecule compounds targeting HDACs are currently undergoing clinical trials for the treatment of cancer, a better understanding of HDAC6-dependent cellular processes would be highly valuable for the evaluation of the clinical relevance and therapeutic efficacy of HDAC6 inhibitors.
Citation Format: Hui Li. HDAC6 modulates colon cancer cell migration and invasion [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3643.
Abstract 367: The role of A20 - Cdc20 axis promotes tumorigenesis and metastasis in triple negative breast cancer
Authors: Song Chaeun 
Published: September 2020

Abstract
Triple negative breast cancer (TNBC) has a higher mitotic index compared to other types of breast cancer yet Ki-67 values are still being used, despite an unclear mechanism. Here we found that the gene Cell-Division Cycle 20 (CDC20), an essential mitotic factor, was highly expressed in TNBC cell lines by using a NCBI GEO database. CDC20 was also negatively correlated with TNBC metastasis and recurrence. CDC20 deficiency results in the decreasing of TNBC cancer cell growth and migration, and mitosis inhibitors blocked TNBC cancer cells growth and metastasis. Interestingly, CDC20 stability is regulated by tumor necrosis factor, alpha-induced protein 3 (TNFAIP3 /A20). CDC20 expression show positive correlation with A20 in TNBC patient samples but not HR positive or HER2 breast cancer patients. A20 deficiency also inhibits cell migration and invasion through the decreasing of CDC20 protein level. Our findings uncover a critical role of the A20-CDC20 axis in tumor growth and metastasis of TNBC and suggest A20 or CDC20 is a novel therapeutic target in TNBC.
Citation Format: Chaeun Song. The role of A20 - Cdc20 axis promotes tumorigenesis and metastasis in triple negative breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 367.
Abstract 3678: The role of SCAMP3 in EGFR trafficking and breast cancer cell response
Authors: Diaz Ariana C. Acevedo , Chea Jael Reyes- , Martinez-Montemayor Michelle M. , Suárez-Arroyo Ivette J. 
Published: September 2020

Abstract
Breast cancer (BC) affects approximately 1 in 8 women and is the second leading cause of cancer among women in the United States. BC tumors frequently overexpress Epidermal Growth Factor Receptor (EGFR) which contributes to BC progression and poor clinical outcomes. Studies associate the endocytosis related protein, Secretory Carrier Membrane Protein 3 (SCAMP3), with the regulation of EGFR recycling and degradation. Recently, we published that SCAMP3 is overexpressed in BC cells and tumors. Others have identified SCAMP3 as an indicator of poor prognosis in hepatocellular carcinoma. Therefore, we hypothesize that SCAMP3 promotes the trafficking of EGFR, induces EGFR signaling and BC progression. To evaluate whether SCAMP3 has a direct interaction with EGFR, we treated SUM-149 (EGFR+) and MDA-MB-468 (EGFR+++) BC cells with 100ng/mL EGF at different time points, then we evaluated the localization of both proteins by immunofluorescence. Results showed that SCAMP3 co-localizes with EGFR at the cytoplasm at early stimulation times and the perinuclear area after 30 mins in both cell lines. To evaluate if SCAMP3 has a role in BC progression, we knocked down SCAMP3 in SUM-149 cells using the CRISPR/Cas9 technique, and we assessed the effects in cell viability, colony, and sphere formation capacity and EGFR signaling. Knockdown (KO) and wild type (WT) cells were treated with the ligand at the same concentration described above for 30 min. Our results showed that SCAMP3 knockdown decreased cell viability, colony number and the area of formed spheres. The activation of ERK1/2 was also reduced in SCAMP3 KO cells. Taken together, SCAMP3 is involved in the internalization of EGFR, cell viability, proliferation, and tumor sphere formation. We conclude that SCAMP3 has an essential role in EGFR trafficking and BC progression through EGFR downstream signaling modulation.
Citation Format: Ariana C. Acevedo Diaz, Jael Reyes- Chea, Michelle M. Martinez-Montemayor, Ivette J. Suárez-Arroyo. The role of SCAMP3 in EGFR trafficking and breast cancer cell response [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3678.
Abstract 368: Defining the invasive gene signature using patient derived pancreatic cancer organoids
Authors: Jeong Yea Ji , Lerner Michael G. , Ge Yuchen , Knutsdottir Hildur , Navarro-Serer Bernat , Chianchiano Peter E. , Ewald Andrew J. , Bader Joel S. , Wood Laura D. 
Published: September 2020

Abstract
Pancreatic cancer mortality is rising due to late detection and established metastasis. Despite the recent advances in cancer research, metastasis research has been hampered by the lack of models that recapitulate this complex process. Traditional cell culture and animal models provided insights on cancer cell migration and dissemination. But local invasion, which precedes all the events in the metastatic cascade, remains poorly understood. Patient-derived organoids (PDO) present an innovative platform in which the earliest step of metastasis can be observed and manipulated ex vivo. We developed a pancreatic cancer organoid model using surgically resected tumors from The Johns Hopkins Hospital. We previously reported that there are two invasive patterns in pancreatic cancer PDOs - Mesenchymal and Collective invasion, with one dominating pattern in every PDO culture. Here, we describe the gene expression signature associated with local invasion in pancreatic cancer by comparing the whole transcriptome of matched invasive and non-invasive organoids from the same tumor. For this study, PDOs were cultured for 7 days ex vivo and we manually collected 50 invasive and non-invasive organoids from each culture for RNA-seq analysis. To date, the invasive and non-invasive organoids from 6 PDO lines have been analyzed. The list of differentially expressed genes between invasive and non-invasive organoids includes 1,106 genes with FDR 0.001, with DACT1, DKK3 and KIF26B being most differentially expressed. Pathway analysis identifies that the invasive phenotype is associated with extracellular matrix receptor interaction, focal adhesion and PI3K-Akt signaling pathways. In conclusion, our findings revealed a distinct gene expression signature between invasive and non-invasive cells in PDOs. Interestingly, we did not find significant up or down-regulation in the classical EMT markers in our results, which suggests possible pancreatic cancer-specific metastasis programs exist. We believe our results can inform new diagnostic and prognostic tools and help identify anti-metastasis targets in pancreatic cancer.
Citation Format: Yea Ji Jeong, Michael G. Lerner, Yuchen Ge, Hildur Knutsdottir, Bernat Navarro-Serer, Peter E. Chianchiano, Andrew J. Ewald, Joel S. Bader, Laura D. Wood. Defining the invasive gene signature using patient derived pancreatic cancer organoids [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 368.
Abstract 3702: A lineage-specific lncRNA driven by Foxa1 associated super enhancer promotes tumor growth through interacting YBX1
Authors: Zhang Yin , Huang Yong-xin , Wang Dan-lan , Yan Hai-yan , Dong Yin 
Published: September 2020

Abstract
Lineage-specific expression of genes plays important roles in tumorigenesis. It has been suggested that lncRNAs tend to be more lineage-specifically expressed than protein-coding genes. However, the regulation and role of lineage-specific lncRNAs remains largely unknown. In this study, we reported a lncRNA DSCAM-AS1 that specifically expressed in lung adenocarcinoma and luminal breast cancer. The expression of DSCAM-AS1 was regulated by two super enhancer clusters driven by Foxa1. Foxa1 can directly bind to promoter of DSCAM-AS1. In breast cancer, DSCAM-AS1 was also transcriptionally regulated by ERα, which formed complex with Foxa1. Higher expression of DSCAM-AS1 was associated with poor poor prognosis in both lung adenocarcinoma and luminal breast cancer patients. Silencing or knock-out of DSCAM-AS1 significantly reduce the growth of lung adenocarcinoma and luminal breast cancer cells. We observed silencing or knock-out of DSCAM-AS1 could reduce the expression of Foxa1 in lung adenocarcinoma and breast cancer cells. We also found a significant decrease of ERα expression after silencing or knock-out of DSCAM-AS1 in luminal breast cancer cells. Mechanistically, we found DSCAM-AS1 could interact with YBX1 and enhance recruitment of YBX1 at the promoter region of Foxa1 and ERα. DSCAM-AS1 could form a positive feedback loop with Foxa1 and ERα. Our findings may provide another regulatory loop: Foxa1 and ERα drive expression of super enhancer associated lncRNA DSCAM-AS1 and form a positive feedback loop with it, which play important roles in maintaining cancer cell identity and function.
Citation Format: Yin Zhang, Yong-xin Huang, Dan-lan Wang, Hai-yan Yan, Yin Dong. A lineage-specific lncRNA driven by Foxa1 associated super enhancer promotes tumor growth through interacting YBX1 [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3702.
Abstract 3704: MicroRNA-3977 acts as a tumor suppressor and inhibits triple-negative breast cancer tumorigenesis by targeting FoxM1
Authors: Karamil Selda , Altintas Nuray , Ozpolat Bulent 
Published: September 2020

Abstract
Triple negative breast cancer (TNBC) is an aggressive type of breast cancer characterized by the absence of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). TNBC is associated with poor prognosis, high rates of relapse and distant metastasis despite surgery and adjuvant chemotherapy. The lack of effective targeted therapies for TNBC requires new therapeutic approaches. The Forkhead box protein M1 (FoxM1) is a member of forkhead superfamily transcription factors that has been associated with normal cell growth and proliferation through cell cycle transition and mitotic spindle control. FoxM1 is also identified as a master regulator of tumor metastasis. Based on analysis of pooled clinical datasets derived from online accessible databases as Breast Cancer Gene-Expression Miner v4.3 and Kaplan-Meier plotter, the expression and prognostic values of FoxM1 increase in TNBC compare with other breast cancer subtypes. Directly binding to the 3'-untranslated region (3' UTR) of FoxM1 mRNAs suppress its high expression in TNBC that leads to inhibition of cell proliferation, motility, and invasion. These results implied that FoxM1 is an essential poor prognostic factor and promising candidate target in the treatment of TNBC. We identified miR-3977 as a potential regulator of FoxM1 by using in silico prediction algorithms, and we investigated its role in TNBC. In this study, we found miR-3977 expression is significantly suppressed in TNBC cell lines and inversely correlated with FoxM1 levels. We demonstrate that miR-3977 directly bound to the 3′ UTR of FoxM1 mRNA and repressed its expression. We also find reduced miR-3977 expression is associated with shorter patient survival in TNBC based on Kaplan-Meier plotter database. Moreover, in vivo delivery of miR-3977 nanoparticles inhibited FoxM1 expression and tumor growth in TNBC xenograft mouse models. In conclusion, we provide the first evidence that miR-3977 functions as a tumor suppressor and gain of miR-3977 expression leads to decrease in FoxM1 expression and inhibits to cell growth, colony formation, invasion, and progression of TNBC. Taken together, our data suggest that miR-3977-based gene therapy is a potential therapeutic strategy in TNBC.
Citation Format: Selda Karamil, Nuray Altintas, Bulent Ozpolat. MicroRNA-3977 acts as a tumor suppressor and inhibits triple-negative breast cancer tumorigenesis by targeting FoxM1 [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3704.
Abstract 371: A reporter mouse model enabling image-based evaluation of CD8+T cell dynamics in immunocompetent allografts
Authors: Zhao Bosong , Feng Dan , Zhu Haiyan , Ci Lei , Wan Zhipeng , Sun Ruilin 
Published: September 2020

Abstract
Immune cell recruitment to tumors is indispensable for the success of immunotherapy. In vivo bioluminescence imaging technology to visualize the location and functionality of immune cells is of great value for immuno-oncology research. Here, we describe the generation of a genetically engineered mouse model “Tluc” in whichall CD8+T cells constitutively express a novel luciferase reporter Akaluc. On the C57/BL6 background, the IRES-Akaluc-EGFP expression cassette was placed downstream of the translation stop codon of the endogenous Cd8a gene, allowing the bioluminescence imaging of CD8+T cell location and function under physiological and pathological conditions. As expected, the engineered mice showed constitutive luciferase expression in lymphoid organs such as thymus, lymph nodes and spleen under normal conditions. We next modeled the T cell dynamics in the context of tumor transplantation. In the case of subcutaneously implanted mouse cancer cells such as MC38 colon cancer cells and antigenic SIY-expressing B16 melanoma cells (but not the regular B16 cells), the reporter mice showed T cell recruitment and infiltration into the tumor mass. This apparent immune response was consistent with the simulation. Our study underscores the utilities of such reporter mice for uncovering the role of immune cells in tumor responses by revealing dynamics, interactions and distribution of various immune cells in tumor settings.
Citation Format: Bosong Zhao, Dan Feng, Haiyan Zhu, Lei Ci, Zhipeng Wan, Ruilin Sun. A reporter mouse model enabling image-based evaluation of CD8+T cell dynamics in immunocompetent allografts [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 371.