Exploiting somatic oncogenic driver alterations in a patient with Li-Fraumeni syndrome– paving the path towards precision medicine: a case report by Carolin Seeling, Sonja Dahlum, Ralf Marienfeld, Vera Jan, Brigitte Rack, Uwe Gerstenmaier, Ambros J. Beer, Regine Mayer-Steinacker, Wolfgang Thaiss, Thomas F. E. Barth, Thomas Seufferlein, Nadine T. Gaisa, Stephan Stilgenbauer, Wolfgang Janni, Reiner Siebert, Hartmut Döhner, Verena I. Gaidzik

“…Constitutional genetic germline testing identified a pathogenic TP53 variant in line with the clinical features of Li-Fraumeni syndrome. …”
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ANO7 expression in the prostate modulates mitochondrial function and lipid metabolism by Christoffer Löf, Nasrin Sultana, Neha Goel, Samuel Heron, Gudrun Wahlström, Andrew House, Minna Holopainen, Reijo Käkelä, Johanna Schleutker

“…Previous research, including our own, has shown that germline variants in ANO7 are associated with aggressive PrCa. …”
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Rare Somatic MEN1 Gene Pathogenic Variant in a Patient Affected by Atypical Parathyroid Adenoma by Luigia Cinque, Flavia Pugliese, Celeste Clemente, Stefano Castellana, Maria Pia Leone, Danilo de Martino, Teresa Balsamo, Claudia Battista, Tommaso Biagini, Paolo Graziano, Marco Castori, Alfredo Scillitani, Vito Guarnieri

“…CDC73 gene was screened at germline and somatic levels with no results. Whole exome sequencing performed on DNA extracted from blood leukocytes and tumour tissue revealed a somatic MEN1 gene heterozygous variant, c.912+1G > A, of the splicing donor site of exon 6. …”
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Case report: Deciphering the clinical significance of a novel partial BRCA1 exon 10 duplication in a patient with triple-negative breast cancer by Alice Faversani, Debora Manuelli, Davide Barteselli, Giulia Melloni, Carlo Santaniello, Luigi Corsaro, Luigi Corsaro, Davide Sacco, Davide Sacco, Davide Clerici, Laura Gargiulo, Fulvio Ferrara, Lucy Costantino

“…Pathogenic/likely pathogenic germline variants in the BRCA1 and BRCA2 genes are associated with an increased risk of developing cancer, particularly breast and/or ovarian tumors. …”
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Frequency and Molecular Characteristics of Mismatch Repair-deficient Status among Multiple Synchronous Colorectal Cancers by Kenichi Chikatani, Noriyasu Chika, Noriko Tanabe, Yoshiko Mori, Okihide Suzuki, Takatoshi Matsuyama, Keiichiro Ishibashi, Hidetaka Eguchi, Yasushi Okazaki, Tatsuro Yamaguchi, Hideyuki Ishida

“…When necessary, MLH1-methylation analysis and testing of germline and somatic MMR genes were performed. Results: In total, 133 patients (33 females) had 309 lesions. …”
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A video intervention to improve patient understanding of tumor genomic testing in patients with cancer by Deloris J. Veney, Lai Y. Wei, Amanda E. Toland, Carolyn J. Presley, Heather L. Hampel, Tasleem J. Padamsee, Clara N. Lee, William J. Irvin Jr, Michael J. Bishop, James J. Kim, Shelly R. Hovick, Leigha A. Senter, Daniel G. Stover

“…Results for five questions significantly improved, including the likelihood of TGT impact on treatment decision, incidental germline findings, and cost of testing. Improvement in video message‐specific knowledge was consistent across demographic groups, including age, income, and education. …”
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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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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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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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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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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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