E. Dikoglu, Xu Naizhen, Luke P O'Connor, Peter A. Pinto, M. Merino
{"title":"Abstract 360: The dilemma of the current diagnostic tests for MSI in prostate cancer","authors":"E. Dikoglu, Xu Naizhen, Luke P O'Connor, Peter A. Pinto, M. Merino","doi":"10.1158/1538-7445.AM2021-360","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-360","url":null,"abstract":"Background: Understanding the relationship between tumor genomics and the immune response in cancer has gotten more attention with the advance of immunotherapy. Microsatellite instability (MSI) is a molecular marker that provides prognostic and predictive information in many types of tumors including prostate cancer (PC). In PC, MSI-H and dMMR have been reported anywhere from 1% in primary tumors to up to 12% in metastasis. Reliable testing strategies for MSI/MMR status are critical for clinical management of patients with PC. MSI detection methods include PCR based molecular tests, NGS-based MSI detection or immunohistochemical staining (IHC). We observe technical difficulties in our daily practice with current molecular diagnostic tests. Design: We examined MMR protein expression (MSH2, MSH6, MLH1, PMS2) and PD-L1 by IHC in 30 PC. Results: Among 30 PC tested, 1 tumor (3%) was completely negative for MLH1 and PMS2 and 1 tumor (3%) revealed loss of PMS2 by IHC even though gene panel did not reveal any mutation in PMS2. The PD-L1 IHC was 44% positive, but the single MMR negative biopsy was PD-L1 negative. PD-L1 expression in PC samples did not show correlation with defective MMR expression. Conclusion: In our study, controversial results were obtained. Based on our experience; even though many exons of MMR genes are covered with these panels, there are some exons do not get enough coverage to be analyzed. This low coverage problem creates false negative results. There are also pseudogene pairs of these genes, especially PMS2. For some specific regions, even though there is enough coverage it is impossible to know if the pathogenic variant is on the PMS2 or the pseudogene without additional test. This result suffers from false positive results without a confirmatory test. It is also known that 5% to 11% of MSI-H cases demonstrate intact MMR staining and localization (proficient MMR, pMMR) due to retained antigenicity and nonfunctional protein. So far, in regular practice we use MMR analyzing strategies which set up for colon cancer where the tumor is uniform. PC is more complex; most of the time more than one clone is involving.We believe MSI detection for PC requires improvement the technics of detection, robust set up of testing strategy with high sensitivity and specificity, analyzing strategy and training of pathologists. Due to technical difficulties of the detection, we believe that the prevalence of MSI-high/dMMR PC might be higher than reported in the literature so far. Citation Format: Esra Dikoglu, Xu Naizhen, Luke P. O9Connor, Peter Pinto, Maria J. Merino. The dilemma of the current diagnostic tests for MSI in prostate 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 360.","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81603107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L. Gardner, D. Rothwell, C. Dive, Kostas Kostarelos, Marilena Hadjidemetriou
{"title":"Abstract 568: Nanonets for multiomics blood analysis and cancer biomarker discovery","authors":"L. Gardner, D. Rothwell, C. Dive, Kostas Kostarelos, Marilena Hadjidemetriou","doi":"10.1158/1538-7445.AM2021-568","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-568","url":null,"abstract":"Despite the tremendous potential of liquid biopsies to revolutionise cancer care, there has been limited success translating blood-circulating proteomic and genomic biomarkers into the clinic. This is fundamentally due to the extremely low concentration of tumour-derived biomolecules in blood circulation, particularly at an early disease stage, which makes the discovery phase of the biomarker pipeline extremely challenging. Nanotechnology offers a promising solution, with a nanoparticle-biomolecule enrichment tool recently developed to enrich low-abundant, low molecular weight proteins in the blood of ovarian cancer patients.[1] Proteomic analysis followed by immunoassay-based validation of selected proteins demonstrated the potential of the nanoparticle-platform proposed to discover novel biomarkers with greater specificity and sensitivity than the clinically used biomarkers. In addition, we recently confirmed the presence of cell-free DNA (cfDNA) captured onto the surface lipid nanoparticles incubated ex vivo with human plasma.[2] A significantly higher abundance of cfDNA was detected in the nanoparticle-enriched plasma samples of late-stage ovarian cancer patients compared to age-matched female controls. Proteomic analysis of the same samples also revealed tumour-specific elevations in histone proteins, which are commonly found in circulation complexed with cfDNA. These findings have highlighted the opportunity for the development of a nano-proteogenomics platform able to simultaneously purify both proteins and cell-free nucleic acids from human plasma, an important step in the discovery of novel multi-omic biomarker panels. Utilising the above patented nanotechnology, we have compared proteomic and genomic profiles derived from nanoparticle-biomolecule samples of cancer patients with age- and sex-matched controls to uncover new potential blood-based biomarkers in a proof-of-principle study. In brief, ex-vivo plasma samples were incubated with lipid-based nanoparticles and purified using a two-step size-based purification protocol. The purified samples were then analysed by label-free proteomics (LC-MS/MS) and next-generation sequencing to uncover both proteomic and genomic tumour-specific signatures, including differentially abundant proteins, genomic copy number alterations and tumour-specific mutations. This work highlights the potential of our nanotechnology-based enrichment platform to enhance the discovery of cancer-specific proteogenomic biomarker panels, a vital step in developing sensitive and specific liquid biopsies for the early detection of cancer. References: [1] M. Hadjidemetriou, L. Papafilippou, R. D. Unwin, J. Rogan, A. Clamp, K. Kostarelos, Nano Today 2020, 34, 100901. [2] L. Gardner, J. Warrington, J. Rogan, D. G. Rothwell, G. Brady, C. Dive, K. Kostarelos, M. Hadjidemetriou, Nanoscale Horizons 2020, 5, 1476. Citation Format: Lois Gardner, Dominic G. Rothwell, Caroline Dive, Kostas Kostarelos, Marilena Hadjidemetriou. Nanon","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84249986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Tanemura, Kenta Furukawa, M. Mikamori, Y. Matsuura, Kenichi Matsumoto, T. Asaoka, Y. Urata
{"title":"Abstract 603: Viable circulating tumor cells predict occult metastatic disease and prognosis, and aberrant expression of PD-L1 on viable CTC in pancreatic cancer","authors":"M. Tanemura, Kenta Furukawa, M. Mikamori, Y. Matsuura, Kenichi Matsumoto, T. Asaoka, Y. Urata","doi":"10.1158/1538-7445.AM2021-603","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-603","url":null,"abstract":"","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84488659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chia‐Chi Lin, P. Zucali, B. Carthon, T. Bauer, M. Tucci, A. Italiano, R. Iacovelli, W. Su, C. Massard, Monsoor Saleh, G. Daniele, A. Greystoke, M. Gutierrez, S. Pant, Ying-Chun Shen, M. Perrino, R. Meng, G. Abbadessa, Helen Lee, Yingwen Dong, M. Chiron, Rui Wang, Laure Loumagne, J. Bono
{"title":"Abstract LB040: Targeting CD38 and PD-1 with isatuximab (Isa) plus cemiplimab (Cemi) in patients (pts) with advanced malignancies: Results from a Phase 1/2 open-label, multicenter study","authors":"Chia‐Chi Lin, P. Zucali, B. Carthon, T. Bauer, M. Tucci, A. Italiano, R. Iacovelli, W. Su, C. Massard, Monsoor Saleh, G. Daniele, A. Greystoke, M. Gutierrez, S. Pant, Ying-Chun Shen, M. Perrino, R. Meng, G. Abbadessa, Helen Lee, Yingwen Dong, M. Chiron, Rui Wang, Laure Loumagne, J. Bono","doi":"10.1158/1538-7445.AM2021-LB040","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-LB040","url":null,"abstract":"Background: CD38 is implicated in noncanonical adenosine synthesis and its overexpression on tumor cells has been implicated in T-cell exhaustion and resistance to immune checkpoint blockade. Preclinical data suggest that concurrent treatment of anti-CD38 and anti-PD-1/PD-L1 antibodies substantially reduce primary tumor growth via suppressing acquired resistance to immune checkpoint blockade, and thus enhancing anti-PD-1/PD-L1 efficacy. Methods: This Phase 1/2 study (NCT03367819) enrolled pts with metastatic castration-resistant prostate cancer (mCRPC) or advanced non-small cell lung cancer (NSCLC). The primary objectives of Phase 1 were safety and tolerability of Isa (anti-CD38 monoclonal antibody) + Cemi (anti-PD-1 monoclonal antibody) in pts with mCRPC (naive to anti-PD-1/PD-L1 therapy) or NSCLC (progressed on anti-PD-1/PD-L1-containing therapy). Phase 2 used a Simon9s 2-stage design with response rate (RR) as the primary endpoint. An interim analysis was planned after the first 24 (mCRPC) and 20 (NSCLC) pts receiving Isa+Cemi were enrolled in Phase 2. Tolerability, immunogenicity, pharmacokinetics, pharmacodynamics, and antitumor activity were assessed, including CD38, PD-L1, tumor-infiltrating lymphocytes in the tumor microenvironment (TME), and peripheral immune cell phenotyping. Results: Isa+Cemi demonstrated a manageable safety profile with no new safety signals. All pts experienced ≥1 treatment-emergent adverse event. Grade ≥3 events occurred in 13 (54.2%) mCRPC pts and 12 (60.0%) NSCLC pts. Based on PCWG3 criteria, assessment of best overall response (BOR) with Isa+Cemi in mCRPC revealed no complete responses (CR), 1 unconfirmed partial response (PR) (4.2%), and 5 (20.8%) pts with stable disease (SD). Per RECIST 1.1, NSCLC pts receiving Isa+Cemi achieved no CR or PR, and 13 (65%) achieved SD. Isa+Cemi resulted in ~40% reduction in CD38+ tumor-infiltrating immune cells in post-therapy biopsies. The combination triggered a significant increase in peripheral activated and cytolytic T cells, but decreased NK cells. In addition, low baseline CD38 levels on tumor cells were observed in NSCLC pts who progressed on prior checkpoint inhibitor treatment. No significant modulation of Tregs or PD-L1 in the TME or CD38 expression on tumor cells was observed. Conclusions: The present study suggests that CD38 and PD-1 modulation by Isa+Cemi has a manageable safety profile, reduces CD38+ immune cells in the TME, and activates peripheral T cells; however, this was not associated with significant antitumor activity in these small cohorts of mCRPC and NSCLC pts. Citation Format: Chia-Chi Lin, Paolo Zucali, Bradley Carthon, Todd M. Bauer, Marcello Tucci, Antoine Italiano, Roberto Iacovelli, Wu-Chou Su, Christophe Massard, Monsoor Saleh, Gennaro Daniele, Alastair Greystoke, Martin Gutierrez, Shubham Pant, Ying-Chun Shen, Matteo Perrino, Robin Meng, Giovanni Abbadessa, Helen Lee, Yingwen Dong, Marielle Chiron, Rui Wang, Laure Loumagne, Johann de Bono, Johann","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85989250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Lopategui, Bonnie L. Balzer, Yizhou Wang, C. Santiskulvong, Carissa A. Hyunh, Chun Yat Ong, M. Araña, M. Gayhart, F. Amersi, A. Silberman
{"title":"Abstract 447: Circulating TP53 tumor DNA as a potential biomarker for pre-operative identification of uterine leiomyosarcoma","authors":"J. Lopategui, Bonnie L. Balzer, Yizhou Wang, C. Santiskulvong, Carissa A. Hyunh, Chun Yat Ong, M. Araña, M. Gayhart, F. Amersi, A. Silberman","doi":"10.1158/1538-7445.AM2021-447","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-447","url":null,"abstract":"Uterine leiomyosarcoma (LMS) is a highly aggressive but rare malignancy with a dismal prognosis. In nearly all cases, LMS is unsuspected prior to resection for a presumed leiomyoma. The risk of occult uterine LMS is reported to be 0.2% (1 in 500) in the largest cohort study of women undergoing surgery for presumed fibroid disease. The major problem is that there is no reliable preoperative method to distinguish LMS from a leiomyoma (LM) or STUMP (smooth muscle tumor of uncertain malignant potential), and the patient9s prognosis for LMS is even poorer if the tumor is transected, which occurs in procedures performed for LM. Effective therapy for LMS is lacking and most patients eventually succumb to the disease. Thus, there is a considerable need for a reliable preoperative test to triage patients into the proper surgical procedure for LMS. TP53 alterations are reportedly associated with uterine LMS in about 40% of cases. We screened plasma for TP53 variants in patients with pathologically confirmed LMS. We evaluated TP53 circulating tumor DNA (ctDNA) by deep next-generation sequencing in a cohort of 7 patients with LMS, 1 patient with STUMP, and 3 patients with LM. Clinical data were reviewed to assess disease burden. LMS patients9 tumor burden ranged from no evidence to extensive metastatic disease. DNA extraction was performed using the QIAamp DNA Micro Kit, QIAamp DNA FFPE Tissue Kit, or QIAamp MinElute ccfDNA Mini Kit. DNA quality was assessed using the TapeStation Genomic DNA kit. NGS libraries targeting the entire exonic region of the p53 gene were prepared using the QIASeq Targeted DNA Custom Panel. Sequencing was performed on the MiSeq system using 150bp paired end sequencing with a minimum read depth of 2x0.5M reads for plasma and 2x1M reads for formalin-fixed paraffin embedded and fresh-frozen tissue samples. Raw sequencing data were demultiplexed by bcl2fastq to generate the FASTQ files. Then raw sequencing reads were aligned to the human reference genome GRCh38 by BWA-MEM 0.7.9a-r786. SmCounter2 was used for p53 variants calling and variants quality control. We discovered TP53 ctDNA variants in 5 of 7 (71.4%) LMS cases including p.E258V, p.R248Q, P.R337C, p.E221*, p.R174_R175delinsWC, but not in the control cases of LM or STUMP. In the 5 plasma samples with TP53 mutated LMS, the patients had extensive metastatic disease and in the 2 TP53 wild-type LMS and STUMP cases, the patients had no evidence of disease. To our knowledge, this is the first pilot study to demonstrate the comparative use of TP53 ctDNA in patients with LMS, LM, and STUMP. Further study of these rare LMS is needed to determine the preoperative utility of NGS TP53 ctDNA mutational status as a useful molecular biomarker to help guide surgery and avoid unwarranted manipulation and pelvic contamination of undetected LMS. Supported by the Gottlieb, Buss and Snyder Endowments in Surgical Oncology Citation Format: Jean R. Lopategui, Bonnie Balzer, Yizhou Wang, Chintda Santisk","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80928997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jian-Guo Zhou, Hu Ma, U. Gaipl, B. Frey, M. Hecht, R. Fietkau
{"title":"Abstract 382: Longitudinal C-reactive protein (CRP) as an individualized dynamic predictor for metastatic cancer patients treated with immune checkpoint inhibitors: Findings from the prospective ST-ICI cohort","authors":"Jian-Guo Zhou, Hu Ma, U. Gaipl, B. Frey, M. Hecht, R. Fietkau","doi":"10.1158/1538-7445.AM2021-382","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-382","url":null,"abstract":"Background: Numerus studies already proved C-reactive protein (CRP) in pre-treat is a predictive biomarkers to for cancer patients treated with anti-PD(L)-1 antibodies. However, there aren9t any study has evaluated CRP levels longitudinally in patients with immune checkpoint inhibitors (ICIs). This study provides a comprehensive investigation of CRP levels as well as its longitudinal trajectories as a dynamic predictor of treatment response and survival outcome in metastatic cancer patients undergoing immunotherapy with anti PD-1 or anti PD-L1 agents. Methods: A total number of 104 patients were prospectively enrolled. First, multivariate survival analysis for clinical factors, which including cancer types, line of treatment, PD-L1 expression, brain metastases (BM), etc. Then, used multivariate joint modelling of longitudinal and time to event data to establish the relationship between longitudinal CRP and the overall survival (OS). Results: 92/102 patients with more than 2 times CRP results in all of treatment timepoints. Longitudinal CRP levels combine with clinical factors emerged as independent predictors of worse OS (HR of jointed model= 1.82, 95% CI: 1.45-2.32, p Conclusion: Our study highlights longitudinal CRP serves as potential personalized dynamic predictions for immunotherapeutic benefit of metastatic cancer patients. Keywords: metastatic cancers, immune checkpoint inhibitors, C-reactive protein, dynamic predictor Trial registration: Prospectively registered in ClinicalTrials.gov (NCT03453892) on January 24, 2018. Citation Format: Jian-Guo Zhou, Hu Ma, Udo Gaipl, Benjamin Frey, Markus Hecht, Rainer Fietkau. Longitudinal C-reactive protein (CRP) as an individualized dynamic predictor for metastatic cancer patients treated with immune checkpoint inhibitors: Findings from the prospective ST-ICI 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 382.","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"72 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84160275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. Nystuen, A. Bates, K. O'Leary, S. Emma, Elizabeth G. Sumiec, L. Schuler, Z. Morris
{"title":"Abstract 676: Fulvestrant and radiation modify the tumor immune microenvironment in ER+ metastatic breast cancer and cooperate to enhance response to anti-PDL1 checkpoint blockade","authors":"E. Nystuen, A. Bates, K. O'Leary, S. Emma, Elizabeth G. Sumiec, L. Schuler, Z. Morris","doi":"10.1158/1538-7445.AM2021-676","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-676","url":null,"abstract":"","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"58 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78257397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Charles J. Vaske, Christopher J. Troll, Camille Schwartz, Colin Naughton, A. Ali, A. Raza, Varsha Rao, Kelly Harkins-Kincaid, R. Green
{"title":"Abstract 556: Highly complex DNA sequencing library preparation for cfDNA enrichment panels using a single-stranded approach","authors":"Charles J. Vaske, Christopher J. Troll, Camille Schwartz, Colin Naughton, A. Ali, A. Raza, Varsha Rao, Kelly Harkins-Kincaid, R. Green","doi":"10.1158/1538-7445.AM2021-556","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-556","url":null,"abstract":"DNA sequencing library preparation is a crucial step for next-generation sequencing of cell free DNA of plasma for cancer diagnostics. We present SRSLY, a robust single-stranded DNA library preparation method, that generates libraries with unique molecule identifiers (UMIs), with advantages over traditional double-stranded DNA preparations. Using 5 ng of plasma-derived cfDNA from acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and gastrointestinal cancer cases, we prepared both SRSLY and double-stranded DNA (dsDNA) sequencing libraries with UMIs. The libraries were enriched using a Twist Biosciences custom hybridization probe set for an 800 kilobase cancer mutation panel. We sequenced to a panel depth of 1000x to 2000x, after correcting UMI sequences and removing duplicate reads. With comparable fold enrichment and on-target percentages, we observe complexities of 11-21 million unique molecules with SRSLY. This is approximately four times higher than dsDNA complexity of 2.8-4.9 million unique molecules. Using duplicate reads from the same unique molecule, we perform error correction on template read bases and are able to call low-variant allele frequency mutations. In particular, we show an increase in KRAS p.G12D variant allele fraction during progression from MDS to AML. SRSLY shows increased recovery of small fragments over dsDNA preparations and retains the native lengths and termini of all fragments. Apart from improved library complexity, we show that MDS and AML samples can be distinguished from healthy samples by their disrupted genomic profile of short to long fragments, which has been previously demonstrated in solid tumors but not for MDS or AML. Citation Format: Charles J. Vaske, Chris Troll, Camille Schwartz, Colin Naughton, Abdullah Mahmood Ali, Azra Raza, Varsha Rao, Kelly Harkins-Kincaid, Richard Edward Green. Highly complex DNA sequencing library preparation for cfDNA enrichment panels using a single-stranded 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 556.","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"57 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80332934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Morello, Justine Durand, Margaux Seite, V. Thepenier, G. Teppaz, E. Wilhelm, Arianne Desselle, C. Mary, N. Poirier
{"title":"Abstract 692: Optimized antagonist anti-PD-1/IL-7 bispecific antibody to sustain exhausted T cell function and to disarm Treg suppressive activity","authors":"A. Morello, Justine Durand, Margaux Seite, V. Thepenier, G. Teppaz, E. Wilhelm, Arianne Desselle, C. Mary, N. Poirier","doi":"10.1158/1538-7445.AM2021-692","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-692","url":null,"abstract":"","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"192 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76968112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hyojin Kim, Eun Sun Kim, Song Kook Lee, Jeong Hoon Lee, K. Paeng, C. Ock, D. Suh, Kidong Kim, J. No, Yong‐Beom Kim
{"title":"Abstract 617: Artificial intelligence-powered tissue analysis reveals distinct tumor-infiltrating lymphocyte profile as a potential biomarker of molecular subtypes in endometrial cancer","authors":"Hyojin Kim, Eun Sun Kim, Song Kook Lee, Jeong Hoon Lee, K. Paeng, C. Ock, D. Suh, Kidong Kim, J. No, Yong‐Beom Kim","doi":"10.1158/1538-7445.AM2021-617","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-617","url":null,"abstract":"","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"64 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81451015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}