bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 564: BRAFV600 mutation in circulating tumor DNA can predict outcomes in early-stage melanoma
Authors: Gouda Mohamed Alaa , Polivka Jiri , Huang Helen , Treskova Inka , Pivovarcikova Kristyna , Meric-Bernstam Funda , Pesta Martin , Janku Filip 
Published: July 2021

Abstract
Background: Up to 70% of patients with resected high-risk melanoma develop disease recurrence within 5 years. Adjuvant immunotherapy or targeted therapy can reduce the recurrence rate below approximately 60%. It is, however, at the cost of possible toxicity including long-term side effects. We hypothesize that detection of plasma-derived circulating tumor DNA (ctDNA) from patients with resected melanoma can identify patients at high-risk of disease recurrence.
Methods: We developed an ultrasensitive and specific droplet digital PCR (ddPCR) - based method (Bio-Rad) to detect BRAFV600E-mutated ctDNA in pre-amplified cell-free DNA with sensitivity up to 2 mutant copies in the wild-type background. Plasma samples from patients with surgically resectable melanoma were collected before and after surgery and during follow-up visits for BRAFV600E ctDNA detection. Results obtained from ddPCR analysis were correlated with clinical outcomes.
Results: Total of 53 patients with resectable melanoma (29 males [54.7%]; 15 stage III [28.3%], 22 stage II [41.5%], 10 stage I [18.9%], 3 CIS [5.7%]; 25 with mutant tissue BRAF [47.2%]) and a median age of 60 years were included in the study. BRAFV600E-mutated ctDNA was detected in 25 patients (48%) before surgery and in 17 patients (32%) after surgery. Conversion of ctDNA BRAF status (from mutant to wild-type) in preoperative and postoperative samples occurred in 11 patients (21%). Patients with detectable ctDNA in samples collected after surgery had more disease recurrences (47.1% [n=8] vs. 20.6% [n=7]; P&lt;0.05) and shorter disease-free survival (26 months vs unreached median survival; P&lt;0.05) - and in the cohort of patients with confirmed BRAFV600E mutation in tumor tissue shorter overall survival (35 months versus unreached median survival; P&lt;0.05). At all other studied follow up timepoints, there was no significant difference in outcomes between patients with BRAFV600E-mutated ctDNA and those without.
Conclusions: Our results demonstrate that ultrasensitive droplet digital PCR method can detect ctDNA in patients with resectable melanoma and that patients with detectable ctDNA in blood samples collected after surgery have inferior clinical outcomes.
Citation Format: Mohamed Alaa Gouda, Jiri Polivka, Helen Huang, Inka Treskova, Kristyna Pivovarcikova, Funda Meric-Bernstam, Martin Pesta, Filip Janku. BRAFV600 mutation in circulating tumor DNA can predict outcomes in early-stage melanoma [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 564.
Abstract 583: Analysis of solid pediatric tumor methylomes reveals a shared cancer recurrence signature in cell-free DNA
Authors: Buckley David N. , Tew Ben , Gooden Gerald , Triche Timothy , Salhia Bodour 
Published: July 2021

Abstract
Cancer is the second most common cause of death in children aged 1-14 years in the United States, with approximately 11,000 new cases and 1200 deaths annually. Due in part to the rarity and diversity of childhood tumors, a non-invasive diagnostic to identify patients at high risk of recurrence does not exist for patients with pediatric solid cancer. Cell-free (cf)DNA is rapidly becoming the standard for non-invasive screening, diagnosis, treatment and monitoring of human tumors. In particular, cfDNA methylation detection has proven to be a robust platform for “liquid biopsies,” with several important advantages over simple somatic variant detection. Here we present a cfDNA methylation signature derived from a pan-methylome analysis of recurrent pediatric tumors. The methylomes spanned 34 tumor tissue samples, 13 patient-matched adjacent normal, and 16 patient-matched plasma samples from 27 individuals, representing 11 different pediatric tumor types, including 10 neuroblastomas, 4 osteosarcomas and 2 hepatoblastomas. In addition, 13 adjacent normal samples and 15 normal plasma samples were used as DNA methylation controls. These samples were obtained from the Pediatric Oncology Experimental Investigators' Consortium (POETIC) under informed consent. DNA methylation was analyzed for all samples by whole genome bisulfite sequencing (WGBS). Using consensus DNA methylation calling, we identified a set of 402 differentially methylated regions (DMR) in genomic DNA from tissue, with substantial enrichment of hypomethylated DMRs across a majority of samples. CpGs that were commonly hypomethylated were combined into consensus ‘hotspots.' In order to discriminate between tumor/normal samples in tissue, we applied supervised machine learning to train a classifier on these 402 features. Mean methylation across these 402 CpG hotspots was significantly (p &lt; 0.01) lower in disease plasma compared to normal control plasma samples. We then tested the classifier on the 16 patient-matched cfDNA samples and achieved a classification accuracy of 95% and an area under the curve (AUC) of 0.935. In summary, we have identified a promising set of DNA methylation features also detected in cfDNA that can potentially be used for recurrence risk stratification and measurable minimal residual disease monitoring in solid pediatric tumors.
Citation Format: David N. Buckley, Ben Tew, Gerald Gooden, Timothy Triche, Bodour Salhia. Analysis of solid pediatric tumor methylomes reveals a shared cancer recurrence signature in cell-free DNA [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 583.
Abstract 620: Interrogating the molecular profile of lung cancer tumors in Puerto Rican Hispanics
Authors: Centeno-Girona Hilmaris , Montes-Rodríguez Ingrid M. , Rivera-Lynch Camila , Soto-Salgado Marievelisse , Rivera Noridza , Cruz-Correa Marcia 
Published: July 2021

Abstract
Background: In the United States, lung cancer accounted for approximately one-quarter of all cancer deaths; meanwhile, it was reported as the second cause of death in Puerto Rico (PR) for 2018. Worldwide, the development of new technologies such as next-generation sequencing (NGS) has allowed describing the profile of tumors and identifying mutation drivers in oncologic patients. The information on these is limited for Puerto Rican Hispanics (PRH).
Methods: Using retrospective data from CARIS Life Sciences from 2015 to 2020, we were able to estimate the prevalence of somatic mutations of 119 PRH with lung cancer. In addition, we compared them with the mutational profiles reported for lung cancer from the TCGA Pan-Lung data available in the cBioPortal for Cancer Genomics. Frequencies and percentages were calculated to describe the data.
Results: The results showed that the 10 most mutated genes for lung cancer tumors in PRH were TP53 (53.7%, n=67), EGFR (20.6%, n=73), KRAS (20.6%, n=73), T.M.L. (14.1%, n=64), APC (11.0, n=73), PTEN (10.3%, n=68), ARID1A (13.6%, n=44), PIK3CA (6.9%, n=73), STK11 (6.9%, n=72), and BRAF (5.5%, n=73). Additionally, only one positive mutation was found in MET (1.4%, n=72), and no mutations were identified in ALK and RET. When comparing to the top 10 tumor mutational profiles from the TCGA study, only BRAF was observed with a mutational frequency of 67.7% (n=1,444).
Conclusion: Understanding the common molecular pathways that affect the PRH population is necessary to develop new therapeutic modalities. Moreover, this preliminary review of oncogenic drivers in PRH with lung cancer will inform clinicians, scientists, and the health community about actionable mutations to guide research, treatment, and health policy efforts.
Citation Format: Hilmaris Centeno-Girona, Ingrid M. Montes-Rodríguez, Camila Rivera-Lynch, Marievelisse Soto-Salgado, Noridza Rivera, Marcia Cruz-Correa. Interrogating the molecular profile of lung cancer tumors in Puerto Rican Hispanics [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 620.
Abstract 622: Gene panel-based immune profiling of human cancers
Authors: De Velasco Marco A. , Kura Yurie , Sakai Kazuko , Fujita Kazutoshi , Nozawa Masahiro , Yoshimura Kazuhiro , Nishio Kazuto , Uemura Hirotsugu 
Published: July 2021

Abstract
It is now well accepted that patients with inflamed tumors are more likely to benefit from immunotherapies targeting immune checkpoints such as CTLA4, PD1 and PD-L1.Several factors determine a tumor's immune status and identifying patients who may benefit from immunotherapy and determining which immune therapy to administer depends largely on the patient's tumor immunophenotype. We have developed an approach for immunoprofiling using a focused gene set (115 genes) and scoring system that assesses cell specific types and immune functions. This approach was developed in a preclinical cancer models and is being evaluated and tested in human cancers. We previously extracted data for the gene set and employed unsupervised network clustering to differentiate and classify cancer samples of patients from The Cancer Genome Atlas (TCGA) into immunologically distinct clusters. Here continue or examination and overview clinical features associated with individual clusters. A total of 8477 patients from the TCGA research network were profiled which included 28 solid cancer types. A total of 10 immune clusters (IC 1-10) were identified with a median cluster size of 971 patients with sizes ranging from 178 to 1570. All cancer types were represented in the ICs with mostly normal distribution except for IC 6 which was composed of 40% breast cancer patients and IC10 of which 1/5 of the cases were head-neck squamous cell carcinomas. ICs 2, 5 and 8 were associated with the poorest survival with median times at 73, 51 and 65 months, respectively. Conversely, patients in IC 9 experienced the longest overall survival, median time 148 months. The aggregate inflammation score, which measures overall tumor inflammation was positively correlated to overall survival (P=0.0109). IC 9 was correlated with the highest survival times and was positively associated with primary signatures related antitumor immunity such as high IFN gamma, cytotoxicity, and CD8 T cell and NK cell signatures. IC 8 was characterized with poor survival times and was associated with signatures related with immunosuppressive cells including granulocytic myeloid derived suppressor cells, M2 polarized macrophages and TH17 T cells, and an adenosine high signature. In addition, cases from this cluster also had low CTL signatures. Our findings show that gene expression data from a focused gene and our scoring algorithm could be used to differentiate and classify patients into various groups of immunologically distinct tumors types.
Citation Format: Marco A. De Velasco, Yurie Kura, Kazuko Sakai, Kazutoshi Fujita, Masahiro Nozawa, Kazuhiro Yoshimura, Kazuto Nishio, Hirotsugu Uemura. Gene panel-based immune profiling of human cancers [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 622.
Abstract 628: Ophtalmological manifestations of acute leukemias at university hospital center Yalgado Ouedrago
Authors: Millogo Kalo Roland , Kabore Delphine , Traore Solo 
Published: July 2021

Abstract
Acute leukaemias constitute 9.04% of malignant hemopathies (Burkina Faso, 2015). Their manifestations are mainly haematological, however other less frequent attacks are possible. We report here for the first time in Burkina Faso, three cases of ocular localizations in young adults. Observation 1: S.I, male, 17-year-old patient, student living in Ouagadougou with a history of recurrent sore throat and ear infections. He was admitted for asthenia and pallor in the context of polytransfusion. The myelogram showed a rich marrow marked by the presence of 15% blast cells. Ophthalmologic examination reported visual acuity of 1/10, stage II proptosis and lower chemosis, and massive retinal and macular hemorrhage. Chemotherapy could not be performed. he died a week later. Observation 2: TB, male, 23-year-old patient, welder, suffering from acute lymphoblastic leukemia diagnosed in front of a severe recurrent anemia and confirmed by a myelogram, showing a rich marrow infiltrated by lymphoblasts representing 47% of the medullary cells. The ophthalmologic examination revealed conjunctival-palpebral infiltration by acute leukemia with myogenic ptosis. The evolution was marked by an improvement in symptoms after a cure according to the Vincristine-Prednisone protocol and he was discharged from hospital weeks later. He was subsequently lost to follow-up. Observation 3: KK male, 25-year-old patient, artisanal miner residing in Ouagadougou with a history of peptic ulcer disease, carrier of acute myeloid leukemia (AML) confirmed by a myelogram. The ophthalmologic examination concludes with a bilateral inflammatory orthopathy with an exposure keratitis on site of AML. He received transfusion of concentrates of red blood cells and platelets, as well as corticosteroid therapy for 04 days. The following was marked by a rapid worsening of the symptoms and the death of the patient a week later. Conclusion: The extra-haematological manifestations of acute leukemia are rare. They are associated with a pejorative prognosis. This series of 03 cases that we report is the first described to date in our context.
Citation Format: Kalo Roland Millogo, Delphine Kabore, Solo Traore. Ophtalmological manifestations of acute leukemias at university hospital center Yalgado Ouedrago [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 628.
Abstract 639: Analysis of DNA minimal residual disease markers in pediatric solid cancers using quantitative real time PCR and droplet digital PCR
Authors: Subhash Vinod Vijay , Kamili Alvin , Erasmus Marie-Wong , Chen Dan , Huang Libby , Tyrell Vanessa , Atkinson Caroline , Venn Nicola , Cowley Mark , Marshall Glenn , Ekert Paul , Henderson Michelle , Sutton Rosemary , Norris Murray , Haber Michelle , Fletcher Jamie , Trahair Toby 
Published: July 2021

Abstract
Background: Minimal Residual Disease (MRD) detection is vital for therapy monitoring and relapse prediction in cancers. While RNA-based MRD assays are shown to be effective at diagnostic time-points, serial response monitoring does not provide additional predictive value.DNA-based assays may be more sensitive and allow longitudinal monitoring of the disease trajectory. This study aimed to develop MRD assays based on whole genome sequencing (WGS) data for high-risk neuroblastoma (HRNB) and Ewing sarcoma (ES) patients, to establish their sensitivity in quantitative PCR (qPCR) anddroplet digital PCR (ddPCR) formats, and to directly compare against RNA-based MRD assays.
Methodology: We analyzed WGS data to identify patient-specific chromosomal breakpoints in HRNB (N=6) and ES (N=6) patients, then established qPCR and ddPCR assays. Assay performance was validated using patient-derived cells spiked into bone marrow samples and in serially collected clinical samples as available. The DNA-MRD markers were compared against a panel of RNA-MRD markers for HRNB (TH/DCX/PHOX2B) and ES (EWS-FLI1/ERG/ETV1).
Results: DNA-MRD markers showed high sensitivity and quantitation ranging from 10-4(0.01%) to 10-5(0.001%) in qPCR assays and ddPCR assays. In clinical samples of HRNB and ES, DNA-MRD markers were detected in diagnosis specimens and predicted disease trajectory. Among RNA-MRD markers, TH & EWS-FLI1 transcripts showed the maximum detection sensitivity (0.01%), however was less sensitive than the patient specific DNA-MRD markers.
Conclusion: This study identifies DNA-MRD analysis as a reliable complimentary approach to RNA-MRD assays and highlights its enhanced sensitivity and clinical utility for monitoring treatment response and disease progression in solid pediatric tumors.
Citation Format: Vinod Vijay Subhash, Alvin Kamili, Marie-Wong Erasmus, Dan Chen, Libby Huang, Vanessa Tyrell, Caroline Atkinson, Nicola Venn, Mark Cowley, Glenn Marshall, Paul Ekert, Michelle Henderson, Rosemary Sutton, Murray Norris, Michelle Haber, Jamie Fletcher, Toby Trahair. Analysis of DNA minimal residual disease markers in pediatric solid cancers using quantitative real time PCR and droplet digital PCR [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 639.
Abstract 65: Therapeutically increasing MHC-I expression potentiates immune checkpoint blockade
Authors: Gu Shengqing , Zhang Wubing , Wang Xiaoqing , Jiang Peng , Traugh Nicole , Li Ziyi , Meyer Clifford , Stewig Blair , Xie Yingtian , Bu Xia , Manos Michael , Font-Tello Alba , Gjini Evisa , Lako Ana , Lim Klothilda , Conway Jake , Tewari Alok , Zeng Zexian , Sahu Avinash Das , Tokheim Collin , Weirather Jason L. , Fu Jingxin , Zhang Yi , Kroger Benjamin , Liang Jin Hua , Cejas Paloma , Freeman Gordon J. , Rodig Scott J. , Long Henry , Gewurz Benjamin E. , Hodi F. Stephen , Brown Myles , Liu X. Shirley 
Published: July 2021

Abstract
Immune checkpoint blockade (ICB) therapy revolutionized cancer treatment, but many patients with impaired MHC-I expression remain refractory. Here, we combined FACS-based genome-wide CRISPR screens with a data-mining approach to identify drugs that can upregulate MHC-I without inducing PD-L1. CRISPR screening identified TRAF3, a critical suppressor of the NF-κB pathway, as a negative regulator of MHC-I but not PD-L1. The Traf3-knockout (Traf3-KO) gene expression signature is associated with better survival in ICB-naive cancer patients and better ICB response. We then screened for drugs with similar transcriptional effects as this signature and identified SMAC mimetics. We experimentally validated that the SMAC mimetic birinapant upregulates MHC-I, sensitizes cancer cells to T-cell-dependent killing, and synergizes with ICB. Our findings provide preclinical rationale for treating tumors expressing low MHC-I expression with SMAC mimetics to enhance sensitivity to immunotherapy. The approach used in this study can be generalized to identify other drugs that enhance immunotherapy efficacy.
Citation Format: Shengqing Gu, Wubing Zhang, Xiaoqing Wang, Peng Jiang, Nicole Traugh, Ziyi Li, Clifford Meyer, Blair Stewig, Yingtian Xie, Xia Bu, Michael Manos, Alba Font-Tello, Evisa Gjini, Ana Lako, Klothilda Lim, Jake Conway, Alok Tewari, Zexian Zeng, Avinash Das Sahu, Collin Tokheim, Jason L. Weirather, Jingxin Fu, Yi Zhang, Benjamin Kroger, Jin Hua Liang, Paloma Cejas, Gordon J. Freeman, Scott J. Rodig, Henry Long, Benjamin E. Gewurz, F. Stephen Hodi, Myles Brown, X. Shirley Liu. Therapeutically increasing MHC-I expression potentiates immune checkpoint blockade [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 65.
Abstract 659: Evaluation of homologous recombination repair related gene mutation on survival and drug response in Chinese epithelial ovarian cancer patients
Authors: Li Lei , Shao Kang , Zhang Jianwei , Liu Meng , Wu Kui , Wu Ming 
Published: July 2021

Abstract
Background: Target sequencing of epithelial ovarian cancer (EOC) has been widely used in clinical to detect the status of BRCA1/2 and genes in homologous recombination repair (HRR) pathway. But there still lacks of systematic evaluation of HRR related gene mutation effect on clinical outcome.
Methods: Totally 230 EOC patient is recruited and received OseqT panel sequencing including 12 HRR related genes, 5 mismatch repair related genes and 8 ovarian cancer related genes. All the patients received platinum-based chemotherapy. 25 of them received PARP inhibitor therapy. Their responses to the therapy, OS and PFS were collected for analysis.
Results: We found that BRCA2 and BRCA1/2 mutation carriers (somatic and germline) had longer OS (p value: 0.016 and 0.028) and PFS (p value: 0.002, 0.006) than non-carriers, PTEN and MSH2 germline mutation carriers had longer PFS (p value: 0.038, 0.049) than non-carries. When we compared germline pathogenic carriers and non-pathogenic carriers on OS and PFS, there is significant difference in PALB2 (p value: 0.036, 0.015) and STK11 (0.001, 0.018), BRCA1 mutation did not affect survival time in both OS and PFS. Then we observed the response to platinum-based chemotherapy. We found that the carriers of germline pathogenic variants in BRCA1, BRCA1/2 and HRR related genes were significant related with better response (p value: 0.16, 0.042 and 0.048), If we combined germline and somatic pathogenic variants together, the p value of BRCA1, BRCA1/2 and HRR related genes were changed to 0.001, 0.009 and 0.001. Somatic status of those gene alone had no relationship with chemotherapy response.In the patients received treatment of PARP inhibitor Niraparib, carriers of germline and somatic pathogenic variant in BRCA1 and BRCA1/2 were more sensitive to Niraparib (p value: 0.18, 0.008), There was only 1 BRCA2 pathogenic carrier and no other HRR related gene pathogenic carrier in 25 patients. So, the sensitivity of BRCA2 and HRR-related gene mutation carriers were not calculated.
Conclusions: In our cohort, BRCA2 and BRCA1/2 mutation carriers had longer OS and PFS than non-carriers. PTEN, MSH2, PALB2 and STK11 mutation status also had relationship with survival in some circumstances, BRCA1, BRCA1/2 and HRR-related genes could all be used to predict drug sensitivity, germline and somatic variant should be combined used to reach better performance.
Citation Format: Lei Li, Kang Shao, Jianwei Zhang, Meng Liu, Kui Wu, Ming Wu. Evaluation of homologous recombination repair related gene mutation on survival and drug response in Chinese epithelial ovarian 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 659.