Transcription factor RUNX1 regulates coagulation factor XIII-A (F13A1): decreased platelet-megakaryocyte F13A1 expression and clot contraction in RUNX1 haplodeficiency by Fabiola Del Carpio-Cano, Natthapol Songdej, Liying Guan, Guangfen Mao, Lawrence E. Goldfinger, Jeremy G.T. Wurtzel, Kiwon Lee, Michele P. Lambert, Mortimer Poncz, A. Koneti Rao

“…Background: Germline RUNX1 haplodeficiency (RHD) is associated with thrombocytopenia, platelet dysfunction, and predisposition to myeloid malignancies. …”
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Profiling of Somatic Mutations in Phaeochromocytoma and Paraganglioma by Targeted Next Generation Sequencing Analysis by Andrea Luchetti, Diana Walsh, Fay Rodger, Graeme Clark, Tom Martin, Richard Irving, Mario Sanna, Masahiro Yao, Mercedes Robledo, Hartmut P. H. Neumann, Emma R. Woodward, Farida Latif, Stephen Abbs, Howard Martin, Eamonn R. Maher

“…At least 12 genes (FH, HIF2A, MAX, NF1, RET, SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, and VHL) have been implicated in inherited predisposition to phaeochromocytoma (PCC), paraganglioma (PGL), or head and neck paraganglioma (HNPGL) and a germline mutation may be detected in more than 30% of cases. …”
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Altered chromatin landscape and 3D interactions associated with primary constitutional MLH1 epimutations by Paula Climent-Cantó, Marc Subirana-Granés, Mireia Ramos-Rodríguez, Estela Dámaso, Fátima Marín, Covadonga Vara, Beatriz Pérez-González, Helena Raurell, Elisabet Munté, José Luis Soto, Ángel Alonso, GiWon Shin, Hanlee Ji, Megan Hitchins, Gabriel Capellá, Lorenzo Pasquali, Marta Pineda

“…Abstract Background Lynch syndrome (LS), characterised by an increased risk for cancer, is mainly caused by germline pathogenic variants affecting a mismatch repair gene (MLH1, MSH2, MSH6, PMS2). …”
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Gene signatures derived from transcriptomic-causal networks stratify colorectal cancer patients for effective targeted therapy by Akram Yazdani, Heinz-Josef Lenz, Gianluigi Pillonetto, Raul Mendez-Giraldez, Azam Yazdani, Hanna Sanoff, Reza Hadi, Esmat Samiei, Alan P. Venook, Mark J. Ratain, Naim Rashid, Benjamin G. Vincent, Xueping Qu, Yujia Wen, Michael Kosorok, William F. Symmans, John Paul Y. C. Shen, Michael S. Lee, Scott Kopetz, Andrew B. Nixon, Monica M. Bertagnolli, Charles M. Perou, Federico Innocenti

“…This integrative approach involved germline genotype and tumor RNA-seq data from 1165 metastatic CRC patients. …”
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Intravesical BCG in patients with non-muscle invasive bladder cancer induces trained immunity and decreases respiratory infections by J Alfred Witjes, Alina Vrieling, Mihai G Netea, Leo A B Joosten, Katja K H Aben, Sita H Vermeulen, Joost L Boormans, Antoine G van der Heijden, Boris Novakovic, Jelmer H van Puffelen, Liesbeth van Emst, Denise Kooper, Tahlita C M Zuiverloon, Ursula T H Oldenhof, Tessel E Galesloot, Lambertus A L M Kiemeney, Egbert Oosterwijk

“…An epigenomics approach combining chromatin immuno precipitation-sequencing and RNA-sequencing with in vitro trained immunity experiments identified enhanced inflammasome activity in BCG-treated individuals. Finally, germline variation in genes that affect trained immunity was associated with recurrence and progression after BCG therapy in NMIBC.Conclusion We conclude that BCG immunotherapy induces trained immunity in NMIBC patients and this may account for the protective effects against respiratory infections. …”
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Whole-genome sequencing identifies novel loci for keratoconus and facilitates risk stratification in a Han Chinese population by Yinghao Yao, Xingyong Li, Lan Wu, Jia Zhang, Yuanyuan Gui, Xiangyi Yu, Yang Zhou, Xuefei Li, Xinyu Liu, Shilai Xing, Gang An, Zhenlin Du, Hui Liu, Shasha Li, Xiaoguang Yu, Myopia Associated Genetics Intervention and Consortiums, Hua Chen, Jianzhong Su, Shihao Chen

“…Results The characterization of germline variants entailed correction for population stratification and validation of the East Asian ancestry of the included samples via principal component analysis. …”
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The effect of HLA genotype on disease onset and severity in CTLA-4 insufficiency by Sara Posadas-Cantera, Sara Posadas-Cantera, Noriko Mitsuiki, Florian Emmerich, Virginia Patiño, Hanns-Martin Lorenz, Olaf Neth, Ingunn Dybedal, Kjetil Taskén, Alejandro A. Schäffer, Bodo Grimbacher, Bodo Grimbacher, Bodo Grimbacher, Bodo Grimbacher, Laura Gámez-Díaz, Laura Gámez-Díaz

“…IntroductionHuman Cytotoxic-T-lymphocyte-antigen-4 (CTLA-4) insufficiency caused by heterozygous germline mutations in CTLA4 is a complex immune dysregulation and immunodeficiency syndrome presenting with reduced penetrance and variable disease expressivity, suggesting the presence of disease modifiers that trigger the disease onset and severity. …”
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An exceptionally rare case of a diffuse midline glioma with concomitant H3.1 K27M and G34R mutations in the HIST1H3C (H3C3) gene by Zita Reisz, Rita Pereira, Smitha Nevis, Alan Mackay, Leena Bhaw, Yura Grabovska, Ross Laxton, Valeria Molinari, Anna Burford, Barnaby Clark, Cristina Bleil, Bassel Zebian, Erika Pace, Annette Weiser, Fernando Carceller, Lynley Marshall, Andrew King, Istvan Bodi, Safa Al-Sarraj, Chris Jones, Matthew Clarke

“…Further molecular studies (whole exome, whole genome sequencing) revealed concurrent H3.1 K27M and G34R mutations (clonal, in the same reads) of H3C3, FGF11 and PIK3CA somatic variants, and a pathogenic germline NBN variant. The RNAseq profile clustered with H3K27M-mutant tumours. …”
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Experimental medicine study with stabilised native-like HIV-1 Env immunogens drives long-term antibody responses, but lacks neutralising breadthResearch in context by Katrina M. Pollock, Hannah M. Cheeseman, Leon R. McFarlane, Suzanne Day, Monica Tolazzi, Hannah L. Turner, Jennifer Joypooranachandran, Katsiaryna Shramko, Stefania Dispinseri, Philipp Mundsperger, Ilja Bontjer, Nana-Marie Lemm, Sofia Coelho, Maniola Tanaka, Tom Cole, Bette Korber, Dietmar Katinger, Quentin J. Sattentau, Andrew B. Ward, Gabriella Scarlatti, Rogier W. Sanders, Robin J. Shattock

“…When given alone they are insufficient to induce neutralising antibody titres of significant breadth, but they represent potentially valuable polishing immunogens after germline-targeting. Funding: European Aids Vaccine initiative (EAVI2020) received funding from EU Horizon 2020, grant number 681137. …”
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GATA2 mutated allele specific expression is associated with a hyporesponsive state of HSC in GATA2 deficiency syndrome by Laetitia Largeaud, Vincent Fregona, Laura A. Jamrog, Camille Hamelle, Stéphanie Dufrechou, Naïs Prade, Esmaa Sellam, Pauline Enfedaque, Manon Bayet, Sylvie Hébrard, Mathieu Bouttier, Christine Didier, Bastien Gerby, Eric Delabesse, Marlène Pasquet, Cyril Broccardo

“…Abstract GATA2 germline mutations lead to a syndrome characterized by immunodeficiency, vascular disorders and myeloid malignancies. …”
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Translational and clinical comparison of whole genome and transcriptome to panel sequencing in precision oncology by Irina A. Kerle, Thomas Gross, Anja Kögler, Jonas S. Arnold, Maximilian Werner, Jan-Niklas Eckardt, Elena E. Möhrmann, Marie Arlt, Barbara Hutter, Jennifer Hüllein, Daniela Richter, Martin M. K. Schneider, Mario Hlevnjak, Lino Möhrmann, Dorothea Hanf, Christoph E. Heilig, Simon Kreutzfeldt, Maria-Veronica Teleanu, Evelin Schröck, Daniel Hübschmann, Peter Horak, Christoph Heining, Stefan Fröhling, Hanno Glimm

“…In this study, we compared whole-exome/whole-genome (WES/WGS) and transcriptome sequencing (TS) with broad panel sequencing by resequencing the same tumor DNA and RNA as well as normal tissue DNA for germline assessment, from 20 patients with rare or advanced tumors, who were originally sequenced by WES/WGS ± TS within the DKFZ/NCT/DKTK MASTER program from 2015 to 2020. …”
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Adenomas from individuals with pathogenic biallelic variants in the MUTYH and NTHL1 genes demonstrate base excision repair tumour mutational signature profiles similar to colorecta... by Romy Walker, Jihoon E. Joo, Khalid Mahmood, Mark Clendenning, Julia Como, Susan G. Preston, Sharelle Joseland, Bernard J. Pope, Ana B.D. Medeiros, Brenely V. Murillo, Nicholas Pachter, Kevin Sweet, Allan D. Spigelman, Alexandra Groves, Margaret Gleeson, Krzysztof Bernatowicz, Nicola Poplawski, Lesley Andrews, Emma Healey, Steven Gallinger, Robert C. Grant, Aung K. Win, John L. Hopper, Mark A. Jenkins, Giovana T. Torrezan, Christophe Rosty, Finlay A. Macrae, Ingrid M. Winship, Daniel D. Buchanan, Peter Georgeson

“…Background: Colorectal cancers (CRCs) from people with biallelic germline likely pathogenic/pathogenic variants in MUTYH or NTHL1 exhibit specific single base substitution (SBS) mutational signatures, namely combined SBS18 and SBS36 (SBS18+SBS36), and SBS30, respectively. …”
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The Regulation and Functions of Endogenous Retrovirus in Embryo Development and Stem Cell Differentiation by Yangquan Xiang, Hongqing Liang

“…In mammalian embryos, ERVs are extensively activated in early embryo development, but with a highly restricted spatial-temporal pattern; and they are drastically silenced during differentiation with exceptions in extraembryonic tissue and germlines. The dynamic activation pattern of ERVs raises questions about how ERVs are regulated in the life cycle and whether they are functionally important to cell fate decision during early embryo and somatic cell development. …”
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The enigma of cancer polyploidy as deciphered by evolutionary cancer cell biology (ECCB) by Vladimir F. Niculescu, Eugenia R. Niculescu

“…As observed in amoebae, DNA double-strand breaks (DSBs) manifest in the homologous recombination (HR) genes of NG germlines and stem cell lineages when exposed to specific hyperoxic conditions, referred to as AMF hyperoxia, characterized by an oxygen content exceeding 6.0%. …”
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Reduction of monoclonal antibody viscosity using interpretable machine learning by Emily K. Makowski, Hsin-Ting Chen, Tiexin Wang, Lina Wu, Jie Huang, Marissa Mock, Patrick Underhill, Emma Pelegri-O’Day, Erick Maglalang, Dwight Winters, Peter M. Tessier

“…Of the three features, most predicted antibodies at risk for high viscosity, including antibodies with diverse antibody germlines in our study (79 mAbs) as well as clinical-stage IgG1s (94 mAbs), are those with low Fv isoelectric points (Fv pIs < 6.3). …”
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