bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2188: Urothelial cancer-GENOmic analysis to improve patient outcomes and research (UC-GENOME): a bladder cancer advocacy network (BCAN) led collaborative research study
Authors: Damrauer Jeffrey S. , Klomp Jeff , Beck Wolfgang , Zhou Mi , Plimack Elizabeth , Galsky Matthew , Grivas Petros , Hahn Noah , O'Donnell Peter , Iyer Gopa , Quinn David I. , Hoadley Katherine A. , Kim William Y. , Milowsky Matthew I. 
Published: July 2021

Abstract
The UC-GENOME study was designed to capitalize on The Cancer Genome Atlas (TCGA) findings in real world patients with metastatic urothelial carcinoma (UC) with co-equal aims: 1) to provide targeted DNA sequencing for potential clinical decision making at no cost to patients; and 2) to create a clinically annotated biorepository (including tissue, plasma, and PBMCs) for collaborative research. Patients with metastatic UC (n=209, median age 68 y, 74% male) were accrued at 8 academic medical centers between 2016-2019. We report on the first analysis of the targeted DNAseq (n=191) and total RNAseq (n=176) from FFPE specimens (n=169 overlap). Recurrently mutated genes were observed in a similar frequency to TCGA, including TP53 (54%), KMT2D (30%), ARID1A (26%) and FGFR3 (18%). Somatic variant patterns were correlated with previously annotated mutational signatures (COSMICv3), revealing a subset of tumors enriched for APOBEC signatures. Molecular subtypes were defined using the Bladder Cancer Molecular Taxonomy Group's consensus subtyping schema (Ba_Sq=54 [31%], Stroma-rich=64 [36%], LumP=26 [15%], LumU=24 [14%], LumNS=4 [2%], NE=4 [2%]). To further understand the tumor immune features and whether they correlate with durable clinical response, tumor microenvironment deconvolution was performed by applying MiXCR and immune gene signatures. An inflamed phenotype and enhanced T cell receptor richness but not clonality was observed within Ba_Sq and Stroma-rich subtypes, which also had the highest disease control rate (CR/PR + SD ~75%) to immunotherapy. The Stroma-rich subtype had the highest disease control rate (~88%) to chemotherapy. Future efforts will leverage the clinical, DNA and RNAseq data along with other biobanked specimens for collaborative research initiatives.
Citation Format: Jeffrey S. Damrauer, Jeff Klomp, Wolfgang Beck, Mi Zhou, Elizabeth Plimack, Matthew Galsky, Petros Grivas, Noah Hahn, Peter O'Donnell, Gopa Iyer, David I. Quinn, Katherine A. Hoadley, William Y. Kim, Matthew I. Milowsky. Urothelial cancer-GENOmic analysis to improve patient outcomes and research (UC-GENOME): a bladder cancer advocacy network (BCAN) led collaborative research study [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 2188.
Abstract 2223: Distinct genomic features of cutaneous, acral and mucosal melanomas in a Chinese retrospective cohort
Authors: Liu Qiuyu , Kong Lingfei , Wang Weiran , Wang Danhua , Ma Tonghui 
Published: July 2021

Abstract
Background: The incidence of each subtype of melanoma in different races and ethnicities is significant differences. Cutaneous melanomas dominate in the Caucasian population. In contrast, melanomas that occur in the Chinese population are mainly arising from non-cutaneous tissue (extremities and mucous). Here, we reported an analysis of genomic features in 97 acral, 52 cutaneous and 18 mucosal melanomas. Methods: Patients (pts) with melanoma were enrolled, and surgical tumor tissues were collected. Mutation profiling was performed by next-generation sequencing (NGS). Results: Comparing to cutaneous melanoma patients (Age 53±11.6), acral (Age 65±11.1, P&lt;0.001) and mucosal (Age 64±9.7, P=0.01) melanomas occurred in older Chinese patients. Mutations were identified in 148 of melanoma patients (88.62%), including 85 acral (87.63%), 47 cutaneous (90.38%) and 16 mucosal (88.89%) melanomas. Mutations of BRAF (25/52) in cutaneous melanoma, NRAS in acral melanoma (22/97) and mucosal melanomas (5/18) were observed as the most commonly genetic variations in different subtype of melanoma, which always occurred mutual exclusivity. Furthermore, focal amplification of 11q13 (CCND1 and FGF3/4/19) was all abundant in acral melanoma (11.34%, 11/97), which was reported to affect the efficacy of immunotherapy. In total, occurrence of BRAF, NRAS, CDKN2A mutations and 11q13 amplification were significantly different in cutaneous and non-cutaneous melanomas, which suggested different pathogenesis. Conclusions: In summary, genomic characterization of melanomas may offer insights into tumorigenesis and identify potential therapeutic targets in this disease.
Citation Format: Qiuyu Liu, Lingfei Kong, Weiran Wang, Danhua Wang, Tonghui Ma. Distinct genomic features of cutaneous, acral and mucosal melanomas in a Chinese retrospective cohort [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 2223.
Abstract 2228: Usage of ctDNA analysis to identify alterations with strong evidence for response or resistance to targeted therapy in patients with NENs
Authors: Du Kunli , She Xueke , Huang Depei , Shen Xudong , Zhang Hushan , Zheng Jianyong 
Published: July 2021

Abstract
Background: Neuroendocrine neoplasias (NENs) are a heterogeneous group of rare tumors scattered throughout the body. For nonresectable advanced NENs, the main treatment approaches including somatostatin analog, multiple TKIs, mTOR inhibitors and peptide receptor radionuclide therapy, whereas platinum-based chemotherapy is the main treatment for advanced high-grade and poorly differentiated NECs. Currently, there is no standard second-line treatment for NECs when disease progression. ctDNA as a non-invasive diagnostic avenue, which might potentially provide treatment guidance in NENs.
Methods: We queried consecutive data from 40 NENs patients who underwent a targeted next-generation sequencing (NGS) assay performed by 3DMed Clinical Laboratory Inc., a College of American Pathologists (CAP) certified and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory of 3D Medicines Inc. between January, 2017 and June, 2020 in China, to identify the alterations detected in ctDNA. The alterations were classified based on the ranking in the OncoKB database as of January 2020.
Results: In total, 40 of NENs patients detected with at least one alteration in ctDNA. The median age was 54 years, including 28 males and 12 females. Overall, 40.0% of patients had a Level 1 alteration, 22.5% of patients had a Level 2 alteration, and 22.5% of patients had a R1 alteration (selected alterations were outlined in Table).
Conclusion: ctDNA analysis could provide information of alterations with strong evidence for targeted therapy or drug resistance based on the OncoKB database classification for NENs. Though the alterations are associated with other specific cancer types, the alterations still illustrate a part of NENs patients might have chance to be benefited from targeted therapy.
AlterationsNumber of patients (%)Total Level 1 Alterations16 (40.0%)PIK3CA7 (17.5%)BRAF V600E2 (5.0%)BRCA22 (5.0%)MSI-H1 (2.5%)Total Level 2 Alterations9 (22.5%)ERBB2 activating4 (10.0%)MET amplication1 (2.5%)Total Level R1 alterations9 (22.5%)KRAS mut9 (22.5%)
Citation Format: Kunli Du, Xueke She, Depei Huang, Xudong Shen, Hushan Zhang, Jianyong Zheng. Usage of ctDNA analysis to identify alterations with strong evidence for response or resistance to targeted therapy in patients with NENs [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 2228.
Abstract 2229: Landscape of RB1 alterations in 22,432 Chinese solid tumor patients
Authors: Wang Nan , She Xueke , Huang Depei , Shen Xudong , Zhang Hushan , Ji Gang 
Published: July 2021

Abstract
Background: The retinoblastoma susceptibility gene (RB1) is one of tumor suppressor genes. This gene is mutated at variable frequencies in a variety of other human cancers. Cancer genome sequencing revealed that most types of cancer with RB1 mutation were retinoblastomas, osteosarcomas, and small-cell lung cancers, and its mutation was also found in other cancer types with a lower frequency, for instance, prostate cancer, breast cancer and etc. RB1 protein plays a prominent role in a variety of molecular processes related to DNA including gene transcription, DNA replication, DNA repair, and mitosis. However, no comprehensive status of RB1 alterations in Chinese populations with solid tumor has been reported yet.
Methods: The Formalin-Fixed Paraffin-Embedded (FFPE) tissues from solid tumor patients who have underwent next-generation sequencing (NGS) from January 01, 2017 to April 15, 2020 in 3DMed Clinical Laboratory Inc. (a College of American Pathologists (CAP) and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory) were analyzed. The diagnosis of the tissues was confirmed by hematoxylin and eosin (H&E) staining. The single nucleotide variants (SNVs), copy number variants (CNVs) and gene rearrangements data of these patients were analyzed.
Results: Of 22,432 Chinese solid tumor patients with more than 20 tumor types (58% males and 42% females, with median age was 60 years), genomic alterations in RB1 were observed in 1712 (7.6%) patients. RB1 mutations occurred most frequently in small cell lung cancer (138/165, 83.6%), followed by neuroendocrine neoplasms (42/170, 24.7%), sarcoma (127/554, 22.9%), biliary tract cancer (40/209, 19.1%), head and neck cancer (4/22, 18.2%), and liver cancer (232/1649, 14.1%). And (185/1712, 10.8%) patients were detected with germline RB1 mutation. When stratified by the mutational types, 1,443 (6.4%) patients were with SNVs, 59 (0.3%) with fusions, and 210 (0.9%) with loss in RB1 gene.
Conclusion: Our results suggested RB1 alteration was widely occurred in solid tumor patients in China, and specific alteration rates differed largely between tumor types. Our study also suggested usage of NGS in the need for individualized characterization of cancers and further investigations are warranted for the cancer treatment upon molecular profiling in the clinical therapeutic setting.
Citation Format: Nan Wang, Xueke She, Depei Huang, Xudong Shen, Hushan Zhang, Gang Ji. Landscape of RB1 alterations in 22,432 Chinese solid tumor patients [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 2229.
Abstract 2235: A comprehensive map of genetic interactions in childhood cancer reveals multiple underlying biological mechanisms
Authors: Daub Josephine , Amini Saman , Ma Xiaotu , Jager Natalie , Zhang Jinghui , Pfister Stefan , Holstege Frank , Kemmeren Patrick 
Published: July 2021

Abstract
Despite increasing survival rates, childhood cancer is still the major cause of disease-related child death in developed countries. Genetic interactions between mutated genes play an important role in cancer development. They can be detected by searching for pairs of mutated genes that co-occur more (or less) often than expected. Co-occurrence suggests a cooperative role in cancer development, while mutual exclusivity points to synthetic lethality, a phenomenon of interest in cancer treatment research. Little is however known about genetic interactions in childhood cancer. Here, we apply a statistical pipeline to detect genetic interactions in a combined dataset comprising over 2,500 tumors from 23 cancer types. The resulting genetic interaction map of childhood cancers comprises 15 co-occurring and 27 mutually exclusive candidates. The biological mechanisms underlying most candidates are either tumor subtype, pathway epistasis or cooperation while synthetic lethality plays a much smaller role. Thus, other explanations beyond synthetic lethality should be considered when interpreting results of genetic interaction tests.
Citation Format: Josephine Daub, Saman Amini, Xiaotu Ma, Natalie Jager, Jinghui Zhang, Stefan Pfister, Frank Holstege, Patrick Kemmeren. A comprehensive map of genetic interactions in childhood cancer reveals multiple underlying biological mechanisms [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 2235.
Abstract 2242: Blood-based genome-wide copy number analysis of 500 cancer patients
Authors: Dai Chao , Wang Amy Xiaohong , Zhao Zhixin , Xie Feng , Zhou Kemin , Luo Shujun , Jia Shidong , Du Pan 
Published: July 2021

Abstract
Copy number variation (CNV) is an important characteristic in cancer genome. Blood-based low-pass whole genome sequencing (LP-WGS) has been increasingly used to identify copy number variations of large genomic ranges in cancer. Conventional LP-WGS data analysis lacks the identification of focal CNV of small genomic ranges and often includes biased estimation of copy-neutral baseline when unbalanced genome-wide copy number changes are present. In this study, we have developed a proprietary algorithm analysis pipeline and leverage PredicineCARE and PredicineATLAS panel-based sequencing platform to identify focal CNVs missed by LP-WGS, and accurately infer copy number neutral baseline for LP-WGS. Here we present plasma-based LP-WGS results from 500 cancer patients, including breast, prostate, pancreatic and lung cancers. Our study demonstrates a cancer type-specific pattern of copy number variation across chromosome arms. The CNV abnormality score we developed in this study can be used to distinguish healthy person from cancer patient, and monitor disease progression for longitudinal patient samples.
Citation Format: Chao Dai, Amy Xiaohong Wang, Zhixin Zhao, Feng Xie, Kemin Zhou, Shujun Luo, Shidong Jia, Pan Du. Blood-based genome-wide copy number analysis of 500 cancer patients [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 2242.
Abstract 2243: Comprehensive genomic profiling - does timing matter
Authors: Thapa Bicky , Ahmed Gulrayz , Lasowski Matthew , Thomas James P. , Reddi Honey V. , Zimmerman Michael T. , Urrutia Raul , Szabo Aniko , George Ben 
Published: July 2021

Abstract
Background: Comprehensive Genomic Profiling (CGP) is performed routinely in patients (pts) with metastatic solid tumors (MSTs) to guide treatment. However, there is variability in the interval between metastatic diagnosis (MDx) and performance of CGP based on histology and/or provider preference. We analyzed the CGP utilization patterns and its impact on outcomes at our academic medical center.
Methods: All MST pts with CGP data (January 2012 - April 2020), their date of MDx, and the date of CGP were identified by electronic medical record review. Pts who had CGP after MDx were divided into tertiles (T1-earliest, T3-latest) within each cancer type, while some pts had CGP performed prior to MDx (pre-mets). Overall survival (OS) was estimated from the time of MDx with left truncation at the CGP time. Cox regression model was used to estimate the impact of ‘timing of CGP' on survival for individual cancer (CA) types.
Results: Among 1,358 pts identified, 710 (52%) were female, 1,109 (82%) Caucasian, 186 (14%) Afro-Americans, and 1,320 (97%) non-Hispanic. Lung (254; 19%), colorectal (203; 15%), gynecologic (121; 8.9%), pancreatic (106; 7.8%) and connective tissue/soft tissue CAs (95; 7%) were the most frequently identified. Sex, race, and ethnicity had no impact on the time interval between MDx and CGP with 2 exceptions - Hispanics with lung CA and females with pancreas CA had delayed CGP compared to non-Hispanics and males respectively (p =0.019, p =0.025). The median time to CGP after MDx was shortest for urothelial CA (2.4 months) and longest for prostate CA (22 months). Pts with lung [T2 Hazard ratio (HR) of 2.25, p&lt;0.001; T3 HR of 2.67, p&lt;0.001], gastro-esophageal (T2 HR of 1.88, p=0.079; T3 HR of 2.49, p= 0.024), and gynecologic CAs (T2 HR of 2.58, p=0.012; T3 HR of 5.19, p=0.003) had better survival if they had CGP performed during the first tertile after MDx.
Conclusion: Early CGP after MDx may have a greater impact on OS in CA types with more actionable therapeutic targets. The inherent bias associated with limiting the analyses only to pts who had CGP performed hampers our ability to contrast these results with those who did not have CGP performed. The establishment of national quality metrics for CGP utilization by CA type is imperative.
Citation Format: Bicky Thapa, Gulrayz Ahmed, Matthew Lasowski, James P. Thomas, Honey V. Reddi, Michael T. Zimmerman, Raul Urrutia, Aniko Szabo, Ben George. Comprehensive genomic profiling - does timing matter [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 2243.
Abstract 2250: Genomic and transcriptomic analyses of desmoid tumor reveals enrichment of transforming growth factor beta responsive signature
Authors: Park Changhee , Yun Kum-Hee , Song Sanghoon , Lee Jin Kyung , Ryu Jiyeon , Oh Bitna , Hwang Sunjin , Hahm Ki Baik , Kim Seung-Jin , Kim Seung Hyun , Ock Chan-Young , Kim Hyo-Song 
Published: July 2021

Abstract
Introduction: Desmoid tumor is a rare aggressive tumor where there is no satisfying systemic treatment. Previous studies showed increased expression of transforming growth factor-β (TGF-β) in the desmoid tumor. Here, we analyzed genomic and transcriptomic data of tumor samples from patients with desmoid tumor to evaluate therapeutic applicability of inhibition of TGF-β response.
Methods: We collected pre-treatment desmoid tumor samples from 31 patients in Yonsei cancer center, (YCC)-desmoid cohort and performed targeted next-generation sequencing and whole RNA sequencing. To compare the data with other cancer types, we used whole exome sequencing and whole RNA sequencing data from sarcoma patients from Yonsei Cancer Center (YCC-sarcoma cohort, n = 17 and n =53, respectively) and The Cancer Genome Atlas (TCGA, n = 9,235). Transcriptomic data was normalized throughout the three cohorts to reduce batch effect. To evaluate the enrichment of TGF-β responsive signature (TBRS) in tumor and microenvironment, we calculated the mean expression values of fibroblast-TBRS (F-TBRS) from previous study.
Results: In the two sarcoma cohorts (YCC-desmoid and YCC-sarcoma cohorts), desmoid tumor samples had the highest F-TBRS score among the various types of sarcoma. When compared with other cancer types in TCGA, desmoid tumor samples showed the higher F-TBRS than all other cancer types except for pancreatic adenocarcinoma. In the desmoid tumor samples, CTNNB1, GNAQ, and APC mutations were the top 3 frequent mutations (23, 19, and 2 samples, respectively). In the merged two sarcoma cohorts, CTNNB1/APC mutation and GNAQ mutation were both associated with higher enrichment in F-TBRS (p &lt; 0.001, respectively).
Conclusion: Desmoid tumors are enriched with expression of genes associated with TGF-β response of fibroblast compared with other cancer types including other sarcomas. In addition, CTNNB1, APC and GNAQ mutations were associated with higher enrichment in TBRS. Therapeutic intervention to decrease the TGF-β response of fibroblast by using TGF-β receptor inhibitor may show clinical benefit in patients with desmoid tumors.
Citation Format: Changhee Park, Kum-Hee Yun, Sanghoon Song, Jin Kyung Lee, Jiyeon Ryu, Bitna Oh, Sunjin Hwang, Ki Baik Hahm, Seung-Jin Kim, Seung Hyun Kim, Chan-Young Ock, Hyo-Song Kim. Genomic and transcriptomic analyses of desmoid tumor reveals enrichment of transforming growth factor beta responsive signature [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 2250.
Abstract 2272: Interrogating RAS isoform and mutational specificity for effectors with bioluminescence resonance energy transfer (BRET)
Authors: Rigby Megan , Columbus John , Wall Vanessa , Esposito Dominic , Turbyville Thomas 
Published: July 2021

Abstract
Mutations in the small GTPases HRAS, NRAS, and splice variants KRAS4a and KRAS4b occur in roughly 20% of all cancers1. Each of these four RAS isoforms share a high degree of homology, yet play distinct biological roles; mouse models devoid of KRAS die mid-gestation, whereas HRAS and NRAS null mice survive2. The occurrence of RAS isoform mutations and their specific oncogenic codon substitutions are non-uniform across cancer types, with KRAS mutations in the G12 position frequently driving colorectal cancer while NRAS Q61 mutations are commonly present in skin cancer1. Several explanations have been proposed for this, including differential regulation at the level of transcription, mRNA stability, translation, and protein stability, along with distinctions in post-translational modification, localization, and tissue-specific availability of effectors3. Subtle differences in the biochemical properties of amino acid substitutions may also influence the dominant mutational forms across cancer types. However, the question of whether RAS isoforms and their specific codon substitutions preferentially engage with certain effectors within a cellular context remains unclear, despite considerable efforts. Here, we utilize bioluminescence resonance energy transfer (BRET) between mVenus- and NanoLuc-tagged recombinant proteins to derive quantitative measurements of effector affinity across RAS isoforms and common mutants. By transiently expressing a fixed concentration of NanoLuc-tagged effectors while titrating increasing amounts of mVenus-tagged RAS in a cellular system, we generated saturation curves that reflect the nature of binding between the protein pair in vivo to help untangle this longstanding question. We further validated interactions by immunoprecipitation, and determined construct expression and colocalization via western blot and confocal microscopy.
1Prior IA, Hood FE, Hartley JL. The frequency of Ras mutations in cancer. Cancer Research 20202Malumbres M, Barbacid M. RAS oncogenes: the first 30 years. Nature Reviews Cancer 2003;3:459-653Li S, Balmain A, Counter CM. A model for RAS mutation patterns in cancers: finding the sweet spot. Nature Reviews Cancer 2018;18:767-77
Citation Format: Megan Rigby, John Columbus, Vanessa Wall, Dominic Esposito, Thomas Turbyville. Interrogating RAS isoform and mutational specificity for effectors with bioluminescence resonance energy transfer (BRET) [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 2272.