Article
Biochemistry & Molecular Biology
Yinglin Lu, Kai Shi, Haobin Wang, Heng Cao, Fan Li, Jing Zhou, Minli Yu, Debing Yu
Summary: Ascorbic acid and 5-AZA promote myogenic differentiation by regulating DNA demethylation and histone modification levels, with Tet2 playing a key role in this process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Andrew Baessler, Camille L. Novis, Zuolian Shen, Jelena Perovanovic, Mark Wadsworth, Kendall A. Thiede, Linda M. Sircy, Malia Harrison-Chau, Nguyen X. Nguyen, Katherine E. Varley, Dean Tantin, J. Scott Hale
Summary: Following viral infection, Tet2-deficient CD4(+) T cells exhibit a preference for differentiating into highly functional germinal center T follicular helper (T-FH) cells. Tet2 coordinates with multiple transcription factors to regulate the demethylation and expression of target genes, including those that inhibit T-FH differentiation.
Article
Multidisciplinary Sciences
Abdul Rehman Khalil Shaikh, Ikram Ujjan, Muhammad Irfan, Arshi Naz, Tahir Shamsi, Muhammad Tariq Masood Khan, Muhammad Shakeel
Summary: The TET2 gene is involved in DNA methylation and epigenetic regulation in acute myeloid leukemia (AML). Studies in Pakistan found a high frequency of TET2 mutations in AML patients, with specific mutations correlated with AML subtypes and karyotypes.
Article
Multidisciplinary Sciences
Maike Bensberg, Olof Rundquist, Aida Selimovic, Cathrine Lagerwall, Mikael Benson, Mika Gustafsson, Hartmut Vogt, Antonio Lentini, Colm E. Nestor
Summary: TET2 silencing in T-ALL is associated with hypermethylation, and treatment with 5-azacytidine can reduce toxicity in TET2-silenced T-ALL cells, leading to stable re-expression of the TET2 gene.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Food Science & Technology
Yangmian Yuan, Chengyu Liu, Xingrui Chen, Yuyan Sun, Mingrui Xiong, Yu Fan, Robert B. Petersen, Hong Chen, Kun Huang, Ling Zheng
Summary: The study suggests that Tet1 plays a crucial role in obesity by promoting lipolysis and reducing obesity. Vitamin C can treat obesity by enhancing Tet1 activity, thus decreasing hepatic steatosis.
MOLECULAR NUTRITION & FOOD RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Wanhai Qin, Bruno Crestani, C. Arnold Spek, Brendon P. Scicluna, Tom van der Poll, JanWillem Duitman
Summary: This study found that TET2 expression is decreased in IPF patients and AEC2 cells, but AEC2-specific TET2 deficiency does not affect bleomycin-induced pulmonary fibrosis.
Article
Multidisciplinary Sciences
Aristeidis G. Telonis, Qin Yang, Hsuan-Ting Huang, Maria E. Figueroa
Summary: DNMT3A and IDH1/2 mutations together regulate the transcriptome and the epigenome in acute myeloid leukemia. The study found that genes with significant expression-methylation correlations are enriched in signaling and metabolic pathways. The common feature of these methylation-regulated genes is the density of MIR retrotransposons in their introns.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Qi Qi, Qianqian Wang, Kailing Liu, Jiangyue Bian, Zhixuan Yu, Jian Hou
Summary: Tet dioxygenases can induce DNA demethylation and play important roles in mammalian development. Overexpression of Tet1 and Tet2 can alter the methylation landscape of zygotes and impair embryonic development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Karishma J. B. Pratt, Jeremy M. Shea, Laura Remesal-Gomez, Gregor Bieri, Lucas K. Smith, Julien Couthouis, Christopher P. Chen, Irena J. Roy, Geraldine Gontier, Saul A. Villeda
Summary: Loss of Tet2 in adult neurons enhances cognitive function, while overexpression of Tet2 impairs memory. Neuronal Tet2 regulates cognitive function by modulating hydroxymethylation of genes involved in synaptic transmission and dendritic complexity.
Article
Biochemistry & Molecular Biology
Ekaterina Romanova, Anatoliy Zubritskiy, Anna Lioznova, Adewale J. Ogunleye, Vasily A. Golotin, Anna A. Guts, Andreas Lennartsson, Oleg N. Demidov, Yulia A. Medvedeva
Summary: Acute myeloid leukemia (AML) is a rapidly progressing disease with a high mortality rate. Mutations in transcription factors RUNX1 and CEBPA in AML patients can affect the methylation of regulatory sites, leading to gene silencing, most likely in a TET2-dependent manner. Demethylation therapy can restore gene expression and increase sensitivity to chemotherapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Lina Hu, Xuanye Zhang, Huifeng Li, Suxia Lin, Shengbing Zang
Summary: Recent advances in exome sequencing and comprehensive genomic studies have provided new insights into the pathogenesis and mutational landscape of Angioimmunoblastic T-cell lymphoma (AITL). The discovery of recurrent mutations in TET2, DNMT3A, IDH2, and RHOA has highlighted their essential role in AITL. Furthermore, the detection of TET2 mutations in bystander B cells in AITL samples has advanced our understanding of the disease's mechanisms and its association with B-cell lymphoma.
Article
Oncology
Feline O. Voss, Nikki B. Thuijs, Sylvia Duin, Mujde Ozer, Marc van Beurden, Johannes Berkhof, Renske D. M. Steenbergen, Maaike C. G. Bleeker
Summary: This study aimed to validate the accuracy of previously identified DNA methylation markers for detection of high-grade vulvar intraepithelial neoplasia (VIN). The best-performing individual marker was found to be SST, detecting 80% of high-grade VIN cases, with excellent detection of HPV-independent VIN, known to have the highest cancer risk. Selection of a marker panel including ZNF582, SST, and miR124-2 also yielded high accuracy for detection of high-grade VIN.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Oncology
Brian M. Reilly, Timothy Luger, Soo Park, Chan-Wang Jerry Lio, Edahi Gonzalez-Avalos, Emily C. Wheeler, Minjung Lee, Laura Williamson, Tiffany Tanaka, Dinh Diep, Kun Zhang, Yun Huang, Anjana Rao, Rafael Bejar
Summary: Mutations in the DNA methylation regulating gene TET2 are associated with response to DNA methyltransferase inhibitors, but the exact mechanisms are still unknown. TET2 loss influences DNA methylation and hydroxymethylation patterns at erythroid gene enhancers during 5-Aza treatment, leading to downregulation of erythroid gene expression. Treatment with 5-Aza disproportionately induces expression of down-regulated genes in TET2KO cells, with dynamic 5mC changes at erythroid gene enhancers playing a key role.
MOLECULAR CANCER RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Edyta Reszka, Ewa Jablonska, Edyta Wieczorek, Peter Valent, Michel Arock, Gunnar Nilsson, Boguslaw Nedoszytko, Marek Niedoszytko
Summary: This article provides an overview of epigenetic changes relevant to systemic mastocytosis, including gene mutations and methylation patterns, as well as discussing pathways and events triggering disease progression. Additionally, the effects of epigenetic targets and drugs on neoplastic mast cells are explored.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Benedict Shi Xiang Lian, Takumi Kawasaki, Norisuke Kano, Daisuke Ori, Moe Ikegawa, Ayako Isotani, Taro Kawai
Summary: This study demonstrates that DNA methylation at specific CpG dinucleotides plays an important regulatory role in Il6 gene expression. Hypomethylation of CpG+286 promotes Il6 expression, while deletion of CpG+348 leads to a reduction in Il6 expression associated with enhanced CTCF binding to the Il6 locus. Moreover, hypomethylation of CpG+286 in alveolar macrophages from aged mice results in higher Il6 expression in response to LPS compared to young mice.
Article
Genetics & Heredity
Riku Katainen, Iikki Donner, Maritta Raisanen, Davide Berta, Anna Kuosmanen, Eevi Kaasinen, Marja Hietala, Lauri A. Aaltonen
Summary: This study identified a variant in the KDM4C gene that was associated with malignancy in an early-onset multi-cancer family, indicating a potential causal role of this mutation in cancer predisposition. Further analysis revealed dysregulation of H3K9 trimethylation and KDM4C-associated genes in individuals carrying the variant, supporting the hypothesis of its pathogenicity.
JOURNAL OF MEDICAL GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Elisa Rahikkala, Lea Urpa, Bishwa Ghimire, Hande Topa, Mitja Kurki, Maryna Koskela, Mikko Airavaara, Eija Hamalainen, Katri Pylkas, Jarmo Korkko, Helena Savolainen, Anu Suoranta, Aida Bertoli-Avella, Arndt Rolfs, Pirkko Mattila, Mark Daly, Aarno Palotie, Olli Pietilainen, Jukka Moilanen, Outi Kuismin
Summary: Biallelic loss-of-function variants in the SMG9 gene cause heart and brain malformation syndrome. This study identified a novel pathogenic variant in SMG9 and demonstrated its impact on gene expression, although it had minimal effect on NMD.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Oncology
Susanna Koivuluoma, Sandra Vorimo, Tiina M. Mattila, Anna Tervasmaki, Timo Kumpula, Outi Kuismin, Robert Winqvist, Jukka Moilanen, Tuomo Mantere, Katri Pylkas
Summary: TINF2 is a critical subunit of the shelterin complex and its mutations are associated with dyskeratosis congenita and breast cancer susceptibility. This study identified a protein truncating variant in TINF2, which was found at a higher frequency in breast cancer cases compared to controls, but still fell within the range of moderate breast cancer risk alleles.
Article
Biochemistry & Molecular Biology
Asa Kolterud, Niko Valimaki, Heli Kuisma, Joonatan Patomo, Sini T. Ilves, Netta Makinen, Jaana Kaukomaa, Kimmo Palin, Eevi Kaasinen, Auli Karhu, Annukka Pasanen, Ralf Butzow, Oskari Heikinheimo, Helena Kopp Kallner, Lauri A. Aaltonen
Summary: This study found that the treatment response of uterine fibroids is influenced by molecular subclasses, with MED12 mutant fibroids having a higher chance of shrinking after ulipristal acetate treatment compared to HMGA2 driven fibroids. Gene expression and DNA methylation analyses also revealed subclass specific differences in progesterone receptor signaling. These findings highlight the importance of considering genetic subclasses in evaluating uterine fibroid therapies.
HUMAN MOLECULAR GENETICS
(2023)
Article
Oncology
Minna Kankuri-Tammilehto, Anna Tervasmaki, Minna Kraatari-Tiri, Elisa Rahikkala, Katri Pylkas, Outi Kuismin
Summary: ATM c.7570G>C variant is confirmed to co-segregate with breast cancer and is significantly associated with breast cancer in a non-selected breast cancer cohort from Northern Finland. This suggests that ATM c.7570G>C variant may be a high-risk allele for breast cancer.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Immunology
Elina A. Tuovinen, Outi Kuismin, Leila Soikkonen, Timi Martelius, Meri Kaustio, Sari Hamalainen, Hanna Viskari, Jaana Syrjanen, Ulla Wartiovaara-Kautto, Kari K. Eklund, Janna Saarela, Markku Varjosalo, Juha Kere, Timo Hautala, Mikko R. J. Seppanen
Summary: The NF-κB family of transcription factors is important in cellular signaling pathways, and NFKB1 variants have been associated with CVID and immunodeficiency. However, the penetrance and prevalence of CVID are relatively low, while inflammatory manifestations are more common.
CLINICAL IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Johannes Luppe, Heinrich Sticht, Francois Lecoquierre, Alice Goldenberg, Kathleen M. Gorman, Ben Molloy, Emanuele Agolini, Antonio Novelli, Silvana Briuglia, Outi Kuismin, Carlo Marcelis, Antonio Vitobello, Anne-Sophie Denomme-Pichon, Sophie Julia, Johannes R. Lemke, Rami Abou Jamra, Konrad Platzer
Summary: The study identified eight individuals with ultra rare variants in STX1A who presented with a spectrum of intellectual disability, autism, and epilepsy. The phenotypic course varied depending on the type of variant, with missense variants mainly causing epilepsy and single amino acid deletions and the splice variant causing intellectual disability and autistic behavior. In silico modeling showed different impaired protein-protein interactions for missense variants and single amino acid deletions. These findings suggest two different pathogenic mechanisms underlying STX1A-related neurodevelopmental disorders.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Oncology
Timo A. Kumpula, Susanna Koivuluoma, Leila Soikkonen, Sandra Vorimo, Jukka Moilanen, Robert Winqvist, Tuomo Mantere, Outi Kuismin, Katri Pylkas
Summary: CHEK2 is a well-established breast cancer susceptibility gene, with the most frequent pathogenic variant being 1100delC, which confers a 2-fold risk for breast cancer. The rare variant CHEK2 c.1312 G > T, p (Asp438Tyr) in the kinase domain of the protein has unclear clinical significance for breast cancer predisposition due to its rarity.
Letter
Immunology
Wenny Santaniemi, Nora Pernaa, Virpi Glumoff, Timo Hautala
JOURNAL OF CLINICAL IMMUNOLOGY
(2023)
Article
Genetics & Heredity
Ceres Fernandez-Rozadilla, Maria Timofeeva, Zhishan Chen, Philip Law, Minta Thomas, Stephanie Bien, Virginia Diez-Obrero, Li Li, Juan Fernandez-Tajes, Claire Palles, Kitty Sherwood, Sarah Harris, Victoria Svinti, Kevin McDonnell, Susan Farrington, James Studd, Peter Vaughan-Shaw, Xiao-ou Shu, Jirong Long, Qiuyin Cai, Xingyi Guo, Yingchang Lu, Peter Scacheri, James Studd, Jeroen Huyghe, Tabitha Harrison, David Shibata, Christopher Haiman, Mathew Devall, Fredrick Schumacher, Marilena Melas, Gad Rennert, Mireia Obon-Santacana, Vicente Martin-Sanchez, Ferran Moratalla-Navarro, Jae Hwan Oh, Jeongseon Kim, Sun Ha Jee, Keum Ji Jung, Sun-Seog Kweon, Min-Ho Shin, Aesun Shin, Yoon-Ok Ahn, Dong-Hyun Kim, Isao Oze, Wanqing Wen, Keitaro Matsuo, Koichi Matsuda, Chizu Tanikawa, Zefang Ren, Yu-Tang Gao, Wei-Hua Jia, John Potter, Mark Jenkins, Aung Ko Win, Rish Pai, Jane Figueiredo, Robert Haile, Steven Gallinger, Michael Woods, Polly Newcomb, David Shibata, Jeremy Cheadle, Richard Kaplan, Timothy Maughan, Rachel Kerr, David Kerr, Iva Kirac, Jan Boehm, Lukka-Pekka Mecklin, Pekka Jousilahti, Paul Knekt, Lauri Aaltonen, Harri Rissanen, Eero Pukkala, Johan Eriksson, Tatiana Cajuso, Ulrika Hanninen, Johanna Kondelin, Kimmo Palin, Tomas Tanskanen, Laura Renkonen-Sinisalo, Brent Zanke, Satu Mannisto, Demetrius Albanes, Stephanie Weinstein, Edward Ruiz-Narvaez, Julie Palmer, Daniel Buchanan, Elizabeth Platz, Kala Visvanathan, Cornelia Ulrich, Erin Siegel, Stefanie Brezina, Andrea Gsur, Peter Campbell, Jenny Chang-Claude, Michael Hoffmeister, Hermann Brenner, Martha Slattery, John Potter, Konstantinos Tsilidis, Matthias Schulze, Marc Gunter, Neil Murphy, Antoni Castells, Sergi Castellvi-Bel, Leticia Moreira, Volker Arndt, Anna Shcherbina, Mariana Stern, Bens Pardamean, Timothy Bishop, Graham Giles, Melissa Southey, Gregory Idos, Kevin McDonnell, Zomoroda Abu-Ful, Joel Greenson, Katerina Shulman, Flavio Lejbkowicz, Kenneth Offit, Yu-Ru Su, Robert Steinfelder, Temitope Keku, Bethany van Guelpen, Thomas Hudson, Heather Hampel, Rachel Pearlman, Sonja Berndt, Richard Hayes, Marie Elena Martinez, Sushma Thomas, Douglas Corley, Paul Pharoah, Susanna Larsson, Yun Yen, Heinz-Josef Lenz, Emily White, Li Li, Kimberly Doheny, Elizabeth Pugh, Tameka Shelford, Andrew Chan, Marcia Cruz-Correa, Annika Lindblom, David Shibata, Amit Joshi, Clemens Schafmayer, Peter Scacheri, Anshul Kundaje, Deborah Nickerson, Robert Schoen, Jochen Hampe, Zsofia Stadler, Pavel Vodicka, Ludmila Vodickova, Veronika Vymetalkova, Nickolas Papadopoulos, Chistopher Edlund, William Gauderman, Duncan Thomas, David Shibata, Amanda Toland, Sanford Markowitz, Andre Kim, Stephen Gruber, Franzel van Duijnhoven, Edith Feskens, Lori Sakoda, Manuela Gago-Dominguez, Alicja Wolk, Alessio Naccarati, Barbara Pardini, Liesel FitzGerald, Soo Chin Lee, Shuji Ogino, Stephanie Bien, Charles Kooperberg, Christopher Li, Yi Lin, Ross Prentice, Conghui Qu, Stephane Bezieau, Catherine Tangen, Elaine Mardis, Taiki Yamaji, Norie Sawada, Motoki Iwasaki, Christopher Haiman, Loic Le Marchand, Anna Wu, Chenxu Qu, Caroline McNeil, Gerhard Coetzee, Caroline Hayward, Ian Deary, Sarah Harris, Evropi Theodoratou, Stuart Reid, Marion Walker, Li Yin Ooi, Victor Moreno, Graham Casey, Stephen Gruber, Ian Tomlinson, Wei Zheng, Malcolm Dunlop, Richard Houlston, Ulrike Peters
Summary: This study identified 205 independent risk associations for colorectal cancer through a genome-wide association study meta-analysis. Transcriptome and methylome analysis further revealed 53 risk associations. These findings provide insights into the genetic and molecular mechanisms of colorectal oncogenesis and suggest potential targets for new treatment and prevention strategies.
Article
Genetics & Heredity
Niko Valimaki, Vilja Jokinen, Tatiana Cajuso, Heli Kuisma, Aurora Taira, Olivia Dagnaud, Sini Ilves, Jaana Kaukomaa, Annukka Pasanen, Kimmo Palin, Oskari Heikinheimo, Ralf Butzow, Lauri A. Aaltonen, Auli Karhu
Summary: Uterine leiomyomas (ULs) are common benign smooth muscle tumors in premenopausal women. Variants in genes encoding subunits of the SRCAP complex (YEATS4, ZNHIT1, DMAP1, and ACTL6A) are significantly associated with ULs. These variants are linked to earlier diagnosis and hysterectomy. These findings establish the inactivation of SRCAP complex genes as a major contributor to moderate-penetrance UL predisposition.
AMERICAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Gastroenterology & Hepatology
Anil K. Giri, Mervi Aavikko, Linnea Wartiovaara, Toni Lemmetyinen, Juha Karjalainen, Juha Mehtonen, Kimmo Palin, Niko Valimaki, Max Tamlander, Riikka Saikkonen, Auli Karhu, Ekaterina Morgunova, Benjamin Sun, Heiko Runz, Priit Palta, Shuang Luo, Heikki Joensuu, Tomi P. Makela, Iiro Kostiainen, Camilla Schalin-Jantti, Aarno FinnGen, Aarno Palotie, Lauri A. Aaltonen, Saara Ollila, Mark J. Daly
Summary: This study is the largest genome-wide association study on small intestinal neuroendocrine tumors (SI-NETs) to date, and it identified 6 significant loci associated with SI-NET risk. Four of these loci are novel, and one of the top hits is a missense variant in the LGR5 gene, a marker of adult intestinal stem cells.
Article
Genetics & Heredity
Prima Sanjaya, Katri Maljanen, Riku Katainen, Sebastian A. Waszak, Lauri O. Aaltonen, Oliver Stegle, Jan Korbel, Esa Pitkaenen
Summary: This study introduces a deep neural network called Mutation-Attention (MuAt) that can learn representations of simple and complex somatic alterations for prediction of tumour types and subtypes. By utilizing the attention mechanism on individual mutations, MuAt models achieved high prediction accuracy on whole genomes and exomes. Furthermore, MuAt models were able to learn clinically and biologically relevant tumour entities, potentially impacting precision cancer medicine.