Article
Multidisciplinary Sciences
Daniel Eriksson, Ellen Christine Royrvik, Maribel Aranda-Guillen, Amund Holte Berger, Nils Landegren, Haydee Artaza, Asa Hallgren, Marianne Aardal Grytaas, Sara Strom, Eirik Bratland, Ileana Ruxandra Botusan, Bergithe Eikeland Oftedal, Lars Breivik, Marc Vaudel, Oyvind Helgeland, Alberto Falorni, Anders Palmstrom Jorgensen, Anna-Lena Hulting, Johan Svartberg, Olov Ekwall, Kristian Johan Fougner, Jeanette Wahlberg, Bjorn Gunnar Nedrebo, Per Dahlqvist, Per Morten Knappskog, Anette Susanne Boe Wolff, Sophie Bensing, Stefan Johansson, Olle Kampe, Eystein Sverre Husebye
Summary: This study conducted the first genome-wide association study on Autoimmune Addison's disease, identifying nine risk loci, including two coding variants in the Autoimmune Regulator (AIRE) gene. These findings highlight the importance of central immunological tolerance and explain a significant portion of heritability.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Andrew R. Marley, Ming Li, Victoria L. Champion, Yiqing Song, Jiali Han, Xin Li
Summary: High citrus consumption may increase melanoma risk, and a genome-wide analysis was conducted to study gene-citrus consumption interactions. Several genetic loci were identified that may elucidate the association between citrus consumption and melanoma risk, requiring further studies to confirm these findings.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Article
Immunology
Riad Hajdarevic, Asgeir Lande, Jesper Mehlsen, Anne Rydland, Daisy D. Sosa, Elin B. Strand, Olav Mella, Flemming Pociot, Oystein Fluge, Benedicte A. Lie, Marte K. Viken
Summary: This study, the largest to date, did not identify any ME/CFS risk loci at genome-wide significance. However, it provides data for future studies to accumulate the power needed to reach genome-wide significance.
BRAIN BEHAVIOR AND IMMUNITY
(2022)
Article
Oncology
Qianxing Mo, Lixin Wan, Michael J. Schell, Heather Jim, Shelley S. Tworoger, Guang Peng
Summary: Uveal melanoma is a heterogeneous disease characterized by accumulative alterations at multi-omics levels, in which integrative analysis reveals the molecular subtypes and subtype-specific biomarkers that can be used for prognosis and targeted therapy. The integrative molecular classification of UM is primarily driven by DNA copy number variations, differential methylation and expression of genes, and differential mutation of certain genes, which can be used for patient stratification towards personalized management and surveillance.
Article
Multidisciplinary Sciences
Triin Laisk, Maarja Lepamets, Mariann Koel, Erik Abner, Andres Metspalu, Reedik Maegi
Summary: Pernicious anemia is a rare condition with a clear autoimmune basis, often caused by autoimmune gastritis, and associated with a higher risk of other autoimmune disorders. A genome-wide association study meta-analysis identified significant associations between pernicious anemia and genetic risk factors in genes such as PTPN22, PNPT1, HLA-DQB1, IL2RA, and AIRE.
NATURE COMMUNICATIONS
(2021)
Article
Immunology
Lea C. Castellucci, Lucas Almeida, Svetlana Cherlin, Michaela Fakiola, Richard W. Francis, Edgar M. Carvalho, Anadilton Santos da Hora, Taina Souza do Lago, Amanda B. Figueiredo, Clara M. Cavalcanti, Natalia S. Alves, Katia L. P. Morais, Andrea Teixeira-Carvalho, Walderez O. Dutra, Kenneth J. Gollob, Heather J. Cordell, Jenefer M. Blackwell
Summary: This study identified 32 genomic loci associated with cutaneous leishmaniasis, with 6 most plausible genetic risk loci being SERPINB10, CRLF3, STX7, KRT80, LAMP3, and IENG-AS1. Several of these genes showed differential expression in CL biopsies compared to normal skin, with LAMP3, STX7, and CRLF3 being upregulated and KRT80 being downregulated. Cis-eQTLs across SERPINB10 mapped to chromatin interaction regions of different cell types, while those at IFNG-AS1 mapped to transcriptional/enhancer regions in T, natural killer, and B cells.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Oncology
Shaheer Khan, Jose Lutzky, Alexander N. N. Shoushtari, Joanne Jeter, Brian Marr, Thomas E. E. Olencki, Colleen M. M. Cebulla, Mohamed Abdel-Rahman, J. William Harbour, Naomi Sender, Alexandra Nesson, Shahnaz Singh-Kandah, Susana Hernandez, Jeanelle King, Manpreet S. S. Katari, Lyssa Dimapanat, Stephanie Izard, Grazia Ambrosini, Oliver Surriga, Alex J. J. Rai, Codruta Chiuzan, Gary K. K. Schwartz, Richard D. D. Carvajal
Summary: The use of adjuvant crizotinib did not result in improved recurrence-free survival in patients with high-risk uveal melanoma. The analysis of blood extracellular vesicles showed potential for use as a biomarker.
FRONTIERS IN ONCOLOGY
(2022)
Article
Cell Biology
Ruikun Cai, Yichao Dong, Mingxia Fang, Yuxuan Fan, Zian Cheng, Yue Zhou, Jianen Gao, Feifei Han, Changlong Guo, Xu Ma
Summary: SAPHO syndrome, a rare chronic inflammatory disease, is associated with genetic variants and pathways related to osteoclast differentiation and inflammatory reactions, providing insights into its pathogenesis and potential treatment.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Quincy C. C. van den Bosch, Josephine Q. N. Nguyen, Tom Brands, Thierry P. P. van den Bosch, Robert M. Verdijk, Dion Paridaens, Nicole C. Naus, Annelies de Klein, Emine Kilic, Erwin Brosens
Summary: In this study, we reanalyzed publicly available single-cell RNA sequencing data and identified five transcription regulators associated with UM metastasis, with FOXD1 being the most significant. FOXD1 is almost exclusively expressed in high-risk UM and its expression is correlated with poor survival. Elucidating the function and role of FOXD1 in UM could provide insights for understanding and treating UM.
Article
Ophthalmology
Nakul Singh, Rahul Singh, Randy Chris Bowen, Mohamed H. Abdel-Rahman, Arun D. Singh
Summary: This study aimed to estimate the point prevalence of uveal melanoma in patients with germline BAP1 pathogenic variants, finding the prevalence to be 2.8% in the US population. It was also observed that uveal melanoma patients with BAP1 germline pathogenic variants had a lower average age at diagnosis.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2021)
Article
Neurosciences
Meng Song, Jiewei Liu, Yongfeng Yang, Luxian Lv, Wenqiang Li, Xiong-Jian Luo
Summary: Epilepsy, a common brain disorder with a strong genetic component, was the subject of a large-scale genome-wide meta-analysis in this study. Three significant risk loci for epilepsy were identified, and it was suggested that risk variants may influence epilepsy risk through regulating the expression of specific genes. Potential molecular targets for drug development and therapeutics were also highlighted, including GRM3 and TTC21B.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Oncology
Alexej Ballhausen, Elizabeth Urias, Stephen K. Gruschkus, Michelle Williams, Maura S. Glover, Yong Qin, Dan S. Gombos, Sapna P. Patel
Summary: The study found that in uveal melanoma Class 1A patients, those with stage III disease and/or large COMS size are at elevated risk for metastasis. Combined clinical decision-making using AJCC stage and COMS size can have a significant impact on improving risk stratification and adapting follow-up intervals for Class 1A UM patients.
Article
Medicine, Research & Experimental
Tomohito Doke, Shizheng Huang, Chengxiang Qiu, Hongbo Liu, Yuting Guan, Hailong Hu, Ziyuan Ma, Junnan Wu, Zhen Miao, Xin Sheng, Jianfu Zhou, Aili Cao, Jianhua Li, Lewis Kaufman, Adriana Hung, Christopher D. Brown, Richard Pestell, Katalin Susztak
Summary: The study integrated various methods to identify Dachshund homolog 1 (DACH1) as a kidney disease risk gene, revealing its crucial role in regulating the development of renal fibrosis.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Biochemical Research Methods
Ping Hou, Siqi Bao, Dandan Fan, Congcong Yan, Jianzhong Su, Jia Qu, Meng Zhou
Summary: The study identified 40 methylation-driven prognostic genes associated with the tumorigenesis and progression of uveal melanoma, and proposed a 10-gene DNA methylation-driven signature (10MeSig) for predicting patients' survival risk. The 10MeSig was validated in an independent cohort and shown to have similar prognostic value. It was found to be an independent predictive factor for the survival of uveal melanoma patients, improving clinical decisions and providing new insights into the pathogenesis of the disease.
BRIEFINGS IN BIOINFORMATICS
(2021)
Article
Clinical Neurology
Andrew T. Hale, Oluwatoyin Akinnusotu, Jing He, Janey Wang, Natalie Hibshman, Chevis N. Shannon, Robert P. Naftel
Summary: This study is the first genome-wide association study of spastic CP, identifying a SNP (rs78686911) associated with CP by decreasing expression of GRIK4. The findings suggest that genetic variation contributes to the risk of CP.
Article
Urology & Nephrology
Olivier Cussenot, Raphaele Renard-Penna, Sarah Montagne, Valerie Ondet, Antoine Pilon, Jerome Guechot, Eva Comperat, Freddie Hamdy, Alastair Lamb, Geraldine Cancel-Tassin
Summary: This study evaluates different scenarios for the management of early diagnosis of cancer (PCa) in men at high genetic risk using blood and urinary molecular biomarkers in combination with clinical information alongside multiparametric magnetic resonance imaging (mpMRI). The results suggest that screening based on mpMRI is more effective for detecting clinically significant PCa lesions compared to blood markers, and it is recommended to consider a baseline mpMRI for men at high genetic risk starting from the age of 40.
Article
Immunology
Marianne Burbage, Ares Rocarn-Arjo, Blandine Baudon, Yago A. Arribas, Antonela Merlotti, Derek C. Rookhuizen, Sandrine Heurtebise-Chretien, Mengliang Ye, Alexandre Houy, Nina Burgdorf, Guadalupe Suarez, Marine Gros, Benjamin Sadacca, Montserrat Carrascal, Andrea Garmilla, Mylene Bohec, Sylvain Baulande, Berangere Lombard, Damarys Loew, Joshua J. Waterfall, Marc-Henri Stern, Christel Goudot, Sebastian Amigorena
Summary: The noncanonical splice junctions between exons and transposable elements (TEs) have been identified as a source of tumor-specific antigens, and immunization with peptides derived from these junctions can delay tumor growth in mice. Inactivation of TE-silencing genes can result in overexpression of immunogenic junctions.
SCIENCE IMMUNOLOGY
(2023)
Article
Immunology
Antonela Merlotti, Benjamin Sadacca, Yago A. Arribas, Mercia Ngoma, Marianne Burbage, Christel Goudot, Alexandre Houy, Ares Rocafiln-Arjo, Ana Lalanne, Agathe Seguin-Givelet, Marine Lefevre, Sandrine Heurtebise-Chretien, Blandine Baudon, Giacomo Oliveira, Damarys Loew, Montserrat Carrascal, Catherine J. Wu, Olivier Lantz, Marc-Henri Stern, Nicolas Girard, Joshua J. Waterfallz, Sebastian Amigorena
Summary: Noncanonical mRNA splicing events can encode recurrent and immunogenic tumor-specific antigens in NSCLC patients.
SCIENCE IMMUNOLOGY
(2023)
Article
Surgery
Pascale Mariani, Francois-Clement Bidard, Aurore Rampanou, Alexandre Houy, Vincent Servois, Toulsie Ramtohul, Gaelle Pierron, Marion Chevrier, Benjamin Renouf, Olivier Lantz, Sophie Gardrat, Anne Vincent-Salomon, Sergio Roman-Roman, Manuel Rodrigues, Sophie Piperno-Neumann, Nathalie Cassoux, Marc-Henri Stern, Shufang Renault
Summary: This study reports the detection rate and prognostic impact of circulating tumor DNA in patients undergoing surgical resection of liver metastases in uveal melanoma. If confirmed by further studies, this noninvasive biomarker could inform treatment decisions for liver metastases in uveal melanoma patients.
Meeting Abstract
Oncology
D. Rombaut, C. Lefevre, B. Farhat, S. Bondu, A. Letessier, A. Lesieur-Pasquier, D. Castillo-Guzman, M. Leduc, S. Hartono, V. Chesnais, R. Mangione, I. Boussaid, A. Houy, D. Bouscary, L. Willems, N. Chapuis, O. Kosmider, S. Park, S. Raynaud, T. Cluzeau, E. Clappier, P. Fenaux, L. Ades, R. Margueron, M. Wassef, S. Alsafadi, E. Solary, A. Constantinou, M. -H. Stern, B. Palancade, N. Droin, B. Miotto, F. Chedin, M. Fontenay
Article
Multidisciplinary Sciences
Petra ter Brugge, Sarah C. Moser, Ivan Bieche, Petra Kristel, Sabrina Ibadioune, Alexandre Eeckhoutte, Roebi de Bruijn, Eline van der Burg, Catrin Lutz, Stefano Annunziato, Julian de Ruiter, Julien Masliah Planchon, Sophie Vacher, Laura Courtois, Rania El-Botty, Ahmed Dahmani, Elodie Montaudon, Ludivine Morisset, Laura Sourd, Lea Huguet, Heloise Derrien, Fariba Nemati, Sophie Chateau-Joubert, Thibaut Larcher, Anne Salomon, Didier Decaudin, Fabien Reyal, Florence Coussy, Tatiana Popova, Jelle Wesseling, Marc-Henri Stern, Jos Jonkers, Elisabetta Marangoni
Summary: This study demonstrates that shallow HRD can predict the response to platinum-based chemotherapy in TNBC using patient-derived xenografts. Existing methods to identify HRD are controversial, and there is a medical need for predictive biomarkers. Evaluating the response to platinum agents in 55 TNBC patient-derived xenografts, the study found that the HRD status determined from whole genome sequencing can highly predict the response to platinum. Mutations in XRCC3 and ORC1 genes were also found to drive cisplatin response.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Malcy Tarin, Fariba Nemati, Didier Decaudin, Christine Canbezdi, Benjamin Marande, Lisseth Silva, Heloise Derrien, Aart G. Jochemsen, Sophie Gardrat, Sophie Piperno-Neumann, Manuel Rodrigues, Pascale Mariani, Nathalie Cassoux, Marc-Henri Stern, Sergio Roman-Roman, Samar Alsafadi
Summary: Uveal Melanoma (UM) is a rare and malignant intraocular tumor with a poor prognosis. Despite efficient control of the primary tumor, up to 50% of patients develop metastases, mainly in the liver. Inhibitors targeting PKC and MEK have shown limited effectiveness, but the dual inhibition of FAK and MEK, as well as the combination of FAK and PKC inhibitors, hold promise as therapeutic interventions for metastatic UM.
Article
Oncology
Pascale Mariani, Nouritza Torossian, Steven van Laere, Peter Vermeulen, Leanne de Koning, Sergio Roman-Roman, Olivier Lantz, Manuel Rodrigues, Marc-Henri Stern, Sophie Gardrat, Laetitia Lesage, Gabriel Champenois, Andre Nicolas, Alexandre Matet, Nathalie Cassoux, Vincent Servois, Emanuela Romano, Sophie Piperno-Neumann, Claire Lugassy, Raymond Barnhill
Summary: This study investigated the immune cell infiltrates in uveal melanoma liver metastases (UMLM) and found that CD68+ and CD163+ tumor-infiltrating macrophages, CD20+ peritumoral lymphocytes, and growth patterns were important prognostic factors.
BRITISH JOURNAL OF CANCER
(2023)
Article
Genetics & Heredity
Philip Bland, Harry Saville, Patty T. Wai, Lucinda Curnow, Gareth Muirhead, Jadwiga Nieminuszczy, Nivedita Ravindran, Marie Beatrix John, Somaieh Hedayat, Holly E. Barker, James Wright, Lu Yu, Ioanna Mavrommati, Abigail Read, Barrie Peck, Mark Allen, Patrycja Gazinska, Helen N. Pemberton, Aditi Gulati, Sarah Nash, Farzana Noor, Naomi Guppy, Ioannis Roxanis, Guy Pratt, Ceri Oldreive, Tatjana Stankovic, Samantha Barlow, Helen Kalirai, Sarah E. Coupland, Ronan Broderick, Samar Alsafadi, Alexandre Houy, Marc-Henri Stern, Stephen Pettit, Jyoti S. Choudhary, Syed Haider, Wojciech Niedzwiedz, Christopher J. Lord, Rachael Natrajan
Summary: SF3B1 mutations confer sensitivity to poly (ADP-ribose) polymerase inhibitors (PARPi). Mechanistically, this is independent of homologous recombination repair and instead relies on a defective replication stress response due to a reduction of the cyclin-dependent kinase 2 interacting protein (CINP). PARPi treatment of SF3B1 mutant (SF3B1(MUT)) tumors leads to replication stress induced by increased fork origin firing and culminates in cell cycle stalling. SF3B1 hotspot mutations are associated with a poor prognosis in several tumor types and lead to global disruption of canonical splicing.
Article
Cell Biology
David Gentien, Elnaz Saberi-Ansari, Nicolas Servant, Ariane Jolly, Pierre de la Grange, Fariba Nemati, Geraldine Liot, Simon Saule, Aurelie Teissandier, Deborah Bourc'his, Elodie Girard, Jennifer Wong, Julien Masliah-Planchon, Erkan Narmanli, Yuanlong Liu, Emma Torun, Rebecca Goulancourt, Manuel Rodrigues, Laure Villoing Gaude, Cecile Reyes, Mateo Bazire, Thomas Chenegros, Emilie Henry, Audrey Rapinat, Mylene Bohec, Sylvain Baulande, Radhia M'kacher, Eric Jeandidier, Andre Nicolas, Giovanni Ciriello, Raphael Margueron, Didier Decaudin, Nathalie Cassoux, Sophie Piperno-Neumann, Marc-Henri Stern, Johan Harmen Gibcus, Job Dekker, Edith Heard, Sergio Roman-Roman, Joshua J. Waterfall
Summary: Through comprehensive multi-omics characterization, we identified genomic instability as a hallmark of uveal melanoma (UM) and confirmed the recurrent deletion in the BAP1 promoter associated with high risk of metastasis in UM patients. We also discovered the upregulation of PRAME as an independent prognostic biomarker and a potential therapeutic target in UM.
Article
Oncology
Mathieu Chicard, Yasmine Iddir, Julien Masliah Planchon, Valerie Combaret, Valery Attignon, Alexandra Saint-Charles, Didier Frappaz, Cecile Faure-Conter, Kevin Beccaria, Pascale Varlet, Birgit Geoerger, Sylvain Baulande, Gaelle Pierron, Yassine Bouchoucha, Francois Doz, Olivier Delattre, Joshua J. Waterfall, Franck Bourdeaut, Gudrun Schleiermacher
Summary: We demonstrated that cell-free DNA extracted from CSF can be used for whole exome sequencing in pediatric embryonal brain tumors, with informative results in 83% of samples. Clonal heterogeneity was identified in most cases compared to primary tumor tissue sequencing. Nucleosome footprinting at transcription start sites of genes of interest enabled the inference of gene expression. These findings pave the way for the use of CSF cfDNA in molecular diagnosis and disease monitoring.
Meeting Abstract
Oncology
Phil Bland, Harry Saville, Abigail Read, Patty Wai, Gareth Muirhead, Lucinda Curnow, Jadwiga Nieminuszczy, Nivedita Ravindran, Marie John, Somaieh Hedayat, Holly Barker, James Wright, Lu Yu, Ioanna Mavrommati, Barrie Peck, Mark Allen, Patrycja Gazinska, Helen Pemberton, Aditi Gulati, Sarah Nash, Farzana Noor, Naomi Guppy, Ioannis Roxanis, Samantha Barlow, Helen Kalirai, Sarah Coupland, Ronan Broderick, Samar Alsafadi, Alexandre Houy, Marc-Henri Stern, Stephen Pettit, Jyoti Choudhary, Syed Haider, Wojciech Niedzwiedz, Christopher Lord, Rachael Natrajan
Article
Ophthalmology
Sen Ma, Ruben V. Huis In't Veld, Alexander Houy, Marc-Henri Stern, Cadmus Rich, Ferry A. Ossendorp, Martine J. Jager
Summary: The virus-like drug conjugate AU-011 shows potential in inducing immunogenic cell death in uveal melanoma cell lines, which may lead to systemic immune responses and suggests its potential for combination with immunotherapy.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2023)
Article
Oncology
Marie-Charlotte Villy, Anais Le Ven, Marine Le Mentec, Julien Masliah-Planchon, Alexandre Houy, Ivan Bieche, Sophie Vacher, Anne Vincent-Salomon, Catherine Dubois d'Enghien, Mathias Schwartz, Sophie Piperno-Neumann, Alexandre Matet, Denis Malaise, Virginie Bubien, Alain Lortholary, Amal Ait Omar, Mathias Cavaille, Dominique Stoppa-Lyonnet, Nathalie Cassoux, Marc-Henri Stern, Manuel Rodrigues, Lisa Golmard, Chrystelle Colas
Summary: This study finds that monoallelic germline pathogenic variants in the MBD4 gene are associated with susceptibility to uveal melanoma and breast cancer among other cancer types. Further genetic testing and molecular tumor analyses are necessary to better understand the tumor spectrum and estimate the risk associated with this predisposition.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2023)
Article
Biochemistry & Molecular Biology
Celine Callens, Manuel Rodrigues, Adrien Briaux, Eleonore Frouin, Alexandre Eeckhoutte, Eric Pujade-Lauraine, Victor Renault, Dominique Stoppa-Lyonnet, Ivan Bieche, Guillaume Bataillon, Lucie Karayan-Tapon, Tristan Rochelle, Florian Heitz, Sabrina Chiara Cecere, Maria Jesus Rubio Perez, Christoph Grimm, Trine Jakobi Nottrup, Nicoletta Colombo, Ignace Vergote, Kan Yonemori, Isabelle Ray-Coquard, Marc-Henri Stern, Tatiana Popova
Summary: The bevacizumab/olaparib maintenance regimen has been approved for first-line treatment of BRCA-mutated and HRD high-grade advanced ovarian cancer, based on the significantly improved progression-free survival compared to bevacizumab alone. In this study, a new test called shallowHRDv2 was developed as an alternative to MyChoice for HRD detection. The results show that shallowHRDv2 is a high-performing, clinically validated, and cost-effective test for HRD detection.
