Article
Oncology
Katja Goricar, Franja Dugar, Vita Dolzan, Tanja Marinko
Summary: This study investigates the association between homologous recombination repair (HRR) gene polymorphisms and radiotherapy toxicity in early HER2-positive breast cancer. The result suggests that RAD51 and XRCC3 polymorphisms may contribute to adverse events in radiotherapy for early HER2-positive breast cancer patients, potentially serving as predictive biomarkers.
Article
Biochemical Research Methods
Manqi Cai, Molin Yue, Tianmeng Chen, Jinling Liu, Erick Forno, Xinghua Lu, Timothy Billiar, Juan Celedon, Chris McKennan, Wei Chen, Jiebiao Wang
Summary: This study focuses on using cellular deconvolution methods to extract cell-type-specific signals from tissue-level omics data. However, different methods produce different results under various real data settings. The study proposes EnsDeconv, an ensemble deconvolution method that synthesizes the results from multiple single deconvolution methods to achieve robust and accurate estimation of cellular fractions.
Article
Cell Biology
Meena Kusi, Maryam Zand, Li-Ling Lin, Meizhen Chen, Anthony Lopez, Chun-Lin Lin, Chiou-Miin Wang, Nicholas D. Lucio, Nameer B. Kirma, Jianhua Ruan, Tim H. -M. Huang, Kohzoh Mitsuya
Summary: 2-hydroxyglutarate (2HG) suppresses DNA repair, affects chromatin plasticity, and induces cell differentiation and growth in breast cancer cells. Breast tumors with high 2HG exhibit enhanced heterogeneity and adverse prognosis. Ascorbate-2-phosphate can eliminate this heterogeneity and reduce the growth of high 2HG-producing cancer cells.
Article
Cell Biology
Ricardo L. Azevedo-Pereira, Nathan C. Manley, Chen Dong, Yue Zhang, Alex G. Lee, Yulia Zatulovskaia, Varun Gupta, Jennifer Vu, Summer Han, Jack E. Berry, Tonya M. Bliss, Gary K. Steinberg
Summary: Stem cell therapy is promising for multiple disorders, but the interaction between grafted cells and host tissue is not well understood. This study used sequencing tools to decode the transcriptomes of grafted and host cells in a stroke-injured rat brain, and predicted molecular pathways linking host and graft genes. The study identified a potential host-graft crosstalk pathway where BMP6 from the stroke-injured brain induces graft secretion of noggin, a known brain repair factor.
Article
Biochemistry & Molecular Biology
Maxim Sinitsky, Maxim Asanov, Anna Sinitskaya, Daria Shishkova, Maria Khutornaya, Varvara Minina, Anastasia Ponasenko
Summary: This study found that the statin drug atorvastatin can modulate the DNA damage repair response in endothelial cells exposed to MMC, and this response is dependent on the cell line and incubation scheme. This is important for understanding the pleiotropic effects of atorvastatin and can be used to improve the treatment of patients with atherosclerosis characterized by high genotoxic load.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Aditi S. Khatpe, Rebecca Dirks, Poornima Bhat-Nakshatri, Henry Mang, Katie Batic, Sarah Swiezy, Jacob Olson, Xi Rao, Yue Wang, Hiromi Tanaka, Sheng Liu, Jun Wan, Duojiao Chen, Yunlong Liu, Fang Fang, Sandra Althouse, Emily Hulsey, Maggie M. Granatir, Rebekah Addison, Constance J. Temm, George Sandusky, Audrey Lee-Gosselin, Kenneth Nephew, Kathy D. Miller, Harikrishna Nakshatri
Summary: TONSL is upregulated during the initial steps of tumorigenesis to support neoplastic transformation by increasing DNA repair and represents a potential therapeutic target for treating breast cancer.
Article
Biochemistry & Molecular Biology
Nikolett Barta, Nora Ordog, Vasiliki Pantazi, Ivett Berzsenyi, Barbara N. Borsos, Hajnalka Majoros, Zoltan G. Pahi, Zsuzsanna Ujfaludi, Tibor Pankotai
Summary: The selection of suitable reference genes is crucial for molecular analysis in DNA damage-related studies. This study evaluated the expression changes of well-known housekeeping genes following treatment with different DNA-damaging agents and identified the most appropriate reference genes for each treatment.
Article
Oncology
Jiayang Yu, Chun-Guang Wang
Summary: Using a meta-analysis approach, this study found that the G172T polymorphism in the RAD51 gene may be associated with an increased risk of breast cancer, particularly in the Arab population. The association between the XRCC2 R188H polymorphism and breast cancer was not significant. The T241M polymorphism in XRCC3 may be associated with an increased risk of breast cancer, especially in the Asian population.
FRONTIERS IN ONCOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Ying Wu, Zhe Wang, Lu Han, Zhihao Guo, Bohua Yan, Lili Guo, Huadong Zhao, Mengying Wei, Niuniu Hou, Jing Ye, Zhe Wang, Changhong Shi, Suling Liu, Ceshi Chen, Suning Chen, Ting Wang, Jun Yi, JianPing Zhou, Libo Yao, Wenxia Zhou, Rui Ling, Jian Zhang
Summary: Cancer cells regulate their response to the chemotherapeutic drug doxorubicin through RNA m6A modification. They do this by inhibiting RNA m6A modification through PRMT5 and enhancing the nuclear translocation of the demethylase ALKBH5. This leads to increased DNA repair ability and decreased efficacy of doxorubicin. The approved drug tadalafil was identified as a PRMT5 inhibitor that could enhance doxorubicin sensitivity in breast cancer cells by decreasing RNA m6A methylation.
Article
Oncology
Jianfeng He, Caihu Huang, Yanmin Guo, Rong Deng, Lian Li, Ran Chen, Yanli Wang, Jian Huang, Junke Zheng, Xian Zhao, Jianxiu Yu
Summary: SUMOylated PTEN promotes homologous recombination (HR) repair and represses nonhomologous end joining (NHEJ) repair. It dephosphorylates TP53-binding protein 1 (53BP1) to regulate HR repair. Furthermore, SUMOylated PTEN directly and specifically dephosphorylates a specific site on 53BP1, facilitating DNA end resection and ongoing HR repair.
MOLECULAR ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Michael A. Longo, Sunetra Roy, Yue Chen, Karl-Heinz Tomaszowski, Andrew S. Arvai, Jordan T. Pepper, Rebecca A. Boisvert, Selvi Kunnimalaiyaan, Caezanne Keshvani, David Schild, Albino Bacolla, Gareth J. Williams, John A. Tainer, Katharina Schlacher
Summary: In this study, the authors provide insights into the RAD51C-XRCC3 tumor suppressor complex and its role in DNA replication fork protection, restart, and reversal. They present the X-ray co-crystal structure of RAD51C-XRCC3 and define the replication stability roles of RAD51C. Furthermore, they analyze cancer patient mutations and identify distinct interfaces of RAD51C-XRCC3. The study highlights the importance of CX3 in cancer and provides regions for functional testing and classification of cancer mutations.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Adar Yaacov, Shai Rosenberg, Itamar Simon
Summary: The association between mutational signatures and replication timing has been extensively studied in cancer cells but has not been thoroughly explored in non-cancerous cells. In this study, we analyzed 2.9 million somatic mutations across multiple non-cancerous tissues and found that several mutational processes exhibit either early or late replication timing bias. We also compared the replication timing bias of these mutational signatures in normal tissue and matched cancer samples and discovered that SBS1 loses its late replication timing bias in cancer.
SCIENTIFIC REPORTS
(2023)
Article
Cell Biology
Chrysoula Tsirigoti, Mohamad Moustafa Ali, Varun Maturi, Carl-Henrik Heldin, Aristidis Moustakas
Summary: The transcription factor SNAI1 plays an important role in breast cancer by regulating cellular transformation, differentiation and migration. Loss of SNAI1 function may lead to changes in the phenotype of breast cancer cells and an increase in differentiation potential, possibly through the dual transcriptional action of FOXA1 and AR.
CELL DEATH & DISEASE
(2022)
Article
Oncology
Maria Boskovic, Blanka Roje, Felicia Fei-Lei Chung, Andrea Gelemanovic, Vincent Cahais, Cyrille Cuenin, Rita Khoueiry, Katarina Vilovic, Zdenko Herceg, Janos Terzic
Summary: This study found that methylation changes in genes related to muscle and neuronal processes can discriminate between pre-invasive and invasive bladder cancers, suggesting the potential for early diagnosis and targeted therapies.
Article
Biology
Marie Barth, Alicia Toto Nienguesso, Anne Navarrete Santos, Carla Schmidt
Summary: This study quantifies the proteomes of SH-SY5Y cells during neuronal differentiation, revealing differences in protein expression under different conditions and identifying marker proteins for undifferentiated and differentiated cells. The study also explores protein-protein interactions within cells and observes structural reorganization of the actin cytoskeleton during differentiation.
COMMUNICATIONS BIOLOGY
(2022)
Review
Genetics & Heredity
Kateryna Kratzer, Landon J. Getz, Thibaut Peterlini, Jean-Yves Masson, Graham Dellaire
Summary: Gene therapy for genetic diseases has gained increased attention, but faces technical challenges and ethical barriers. Current research is primarily focused on improving gene therapy and gene editing techniques, with less emphasis on the timing and rationale for using such technology.
Article
Biochemistry & Molecular Biology
Ayeong So, Elodie Dardillac, Ali Muhammad, Catherine Chailleux, Laura Sesma-Sanz, Sandrine Ragu, Eric Le Cam, Yvan Canitrot, Jean Yves Masson, Pauline Dupaigne, Bernard S. Lopez, Josee Guirouilh-Barbat
Summary: Selection of DSB repair pathway is crucial for genetic stability. RAD51 plays a role in preventing nonconservative repair by controlling the second step of the repair process in human cells. RAD51's DNA binding ability is required for inhibiting SSA/A-EJ, not GC.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Oncology
Joanne Kotsopoulos, Jan Lubinski, Jacek Gronwald, Janusz Menkiszak, Jeanna McCuaig, Kelly Metcalfe, William D. Foulkes, Susan L. Neuhausen, Sophie Sun, Beth Y. Karlan, Andrea Eisen, Nadine Tung, Olufunmilayo Olopade, Fergus J. Couch, Tomasz Huzarski, Leigha Senter, Louise Bordeleau, Christian F. Singer, Charis Eng, Robert Fruscio, Tuya Pal, Ping Sun, Steven A. Narod
Summary: The study suggests that bilateral oophorectomy is unlikely to determine the risk of breast cancer in BRCA1 mutation carriers, but it should be offered at age 35 to reduce the risk of ovarian and fallopian tube cancer.
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2022)
Article
Oncology
Felix K. F. Kommoss, Basile Tessier-Cloutier, Leora Witkowski, Erna Forgo, Christian Koelsche, Martin Kobel, William D. Foulkes, Cheng-Han Lee, David L. Kolin, Andreas von Deimling, Brooke E. Howitt
Summary: SWI/SNF complex deficiency is common in various cancers, especially in the gynecologic tract. Despite their similar morphology, UDEC, SDUS, and SCCOHT have distinct DNA methylation signatures. Our study highlights the importance of cellular context in determining the epigenetic landscape and suggests that methylation profiling may be a useful diagnostic tool in undifferentiated, SWI/SNF-deficient cancers.
JOURNAL OF PATHOLOGY
(2022)
Editorial Material
Materials Science, Ceramics
A. H. Heuer, M. W. Finnis, W. M. C. Foulkes, A. P. Chen
Summary: This paper comments on recent observations of O and Al self-diffusion in single-crystal sapphire with variable doping concentrations of Mg and Ti. The study suggests that the null effect of aliovalent doping on oxygen diffusivity may be attributed to dopant evaporation near the surface due to extensive heat treatment, whereas an effect on Al diffusivity is still discernible. Furthermore, buffering mechanisms are proposed to be ultimately responsible for modest increases of self-diffusion with respect to dopant concentrations.
JOURNAL OF THE EUROPEAN CERAMIC SOCIETY
(2022)
Article
Geriatrics & Gerontology
Nicole J. Gervais, Laura Gravelsins, Alana Brown, Rebekah Reuben, Laurice Karkaby, Elizabeth Baker-Sullivan, Leanne Mendoza, Claire Lauzon, Anne Almey, William D. Foulkes, Marcus Q. Bernardini, Michelle Jacobson, Lea Velsher, M. Natasha Rajah, Rosanna K. Olsen, Cheryl Grady, Gillian Einstein
Summary: This study found that early midlife bilateral salpingo-oophorectomy (BSO) may be associated with reduced medial temporal lobe structure and function in women, increasing the risk of dementia. Hippocampal subfield volume may be useful for identifying early midlife changes in women at elevated risk for dementia.
NEUROBIOLOGY OF AGING
(2022)
Letter
Oncology
Flavia Watusi de Faria, Elvis Terci Valera, Carla Renata Pacheco Donato Macedo, Erika Furtado Azevedo, Ana Glenda S. Vieira, Gisele E. Martins, Acimar Goncalves da Cunha Junior, Maristella Bergamo Francisco dos Reis, William D. Foulkes, Luiz Fernando Lopes
PEDIATRIC BLOOD & CANCER
(2022)
Article
Pathology
Paul S. Thorner, Anne-Sophie Chong, Javad Nadaf, Naciba Benlimame, Paula Marrano, Rose Chami, Lili Fu, William D. Foulkes
Summary: This study found that PRAME expression occurs in two-thirds of DICER1-related malignancies and may be a marker for the progression of certain DICER1-related lesions, such as PPB and CN. PRAME expression in some tumors, such as RMS, appears to be an intrinsic feature of the tumor, rather than specifically related to DICER1 pathogenic variants.
JOURNAL OF PATHOLOGY CLINICAL RESEARCH
(2022)
Article
Biology
Marjorie Fournier, Amelie Rodrigue, Larissa Milano, Jean-Yves Bleuyard, Anthony M. Couturier, Jacob Wall, Jessica Ellins, Svenja Hester, Stephen J. Smerdon, Laszlo Tora, Jean-Yves Masson, Fumiko Esashi
Summary: The tumour suppressor PALB2 stimulates homologous recombination (HR) repair of DNA damage and protects active genes during DNA replication. Acetylation of the 7K-patch within the PALB2 chromatin association motif (ChAM) by KAT2A/2B enhances PALB2's association with nucleosomes. DNA damage triggers deacetylation of ChAM and increases PALB2's mobility. Mutations in the 7K-patch affect PALB2's chromatin binding, leading to defects in RAD51 foci formation and decreased cell survival.
Correction
Pathology
Paul S. Thorner, Anne-Sophie Chong, Javad Nadaf, Naciba Benlimame, Paula Marrano, Rose Chami, Lili Fu, William D. Foulkes
JOURNAL OF PATHOLOGY CLINICAL RESEARCH
(2022)
Review
Genetics & Heredity
Dylan Pelletier, Barbara Rivera, Marc R. Fabian, William D. Foulkes
Summary: MicroRNAs (miRNAs) are crucial for gene expression regulation, and their biogenesis depends on specific genes such as DROSHA, DGCR8, DICER1, and AGO1/2. Germline pathogenic variants (GPVs) in these genes lead to different genetic syndromes with diverse clinical manifestations. DICER1 GPVs are associated with tumor predisposition, while recent studies have shed light on the clinical consequences of GPVs in DGCR8, AGO1, and AGO2. This review provides an up-to-date summary on how GPVs in miRNA biogenesis genes affect miRNA biology and contribute to clinical manifestations.
TRENDS IN GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Dylan Pelletier, Anne-Laure Chong, Mona Wu, Leora Witkowski, Sophie Albert, Nelly Sabbaghian, Marc R. Fabian, William D. Foulkes
Summary: The endoribonuclease DICER1 is crucial in microRNA biogenesis, generating mature single-stranded miRNAs by cleaving pre-miRNA stem-loops. Pathogenic variants in DICER1 result in DICER1 tumor predisposition syndrome (DTPS), a childhood-onset tumor susceptibility disorder. Germline DICER1 missense variants in the Platform domain have been found in patients with tumors associated with DTPS, which impair miRNA biogenesis by preventing DICER1 from producing mature miRNAs and binding to pre-miRNA stem-loops.
Review
Oncology
Claire Freycon, Philip J. Lupo, Leora Witkowski, Crystal Budd, William D. Foulkes, Catherine Goudie
Summary: This systematic review found that some patients with FOXO1 fusion-positive ARMS have pathogenic/likely pathogenic variants in cancer predisposing genes, but the causal relationship between CPS and FP-ARMS could not be determined. Only one patient was diagnosed with a cancer predisposition syndrome known to be associated with rhabdomyosarcoma. Clinicians cannot solely rely on FOXO1 fusion status to distinguish patients with/without CPS.
PEDIATRIC BLOOD & CANCER
(2023)
Article
Public, Environmental & Occupational Health
Ayelen T. Eberhardt, Melina Simoncini, Carlos Pina, German Galoppo, Virginia Parachu-Marco, Andrea Racca, Sofia Arce, Evangelina Viotto, Florencia Facelli, Florencia Valli, Cecilia Botto, Leonardo Scarpa, Celina Junges, Cintia Palavecino, Camila Beccaria, Diego Sklar, Graciela Mingo, Alicia Genolet, Monica Munoz de Toro, Hugo Aimar, Veronica Marignac, Juan Carlos Bossio, Gustavo Armando, Hugo Fernandez, Pablo M. Beldomenico
Summary: The Omicron variant of SARS-CoV-2 is more infectious and has immune escape capabilities compared to previous variants, leading to a surge in COVID-19 cases worldwide. Despite a high vaccination and infection rate in Santa Fe city, Argentina, the arrival of Omicron caused the largest wave of COVID-19 experienced in the city. A study conducted prior to the arrival of Omicron showed that a majority of sampled individuals had acquired immunity against COVID-19, but antibody levels varied depending on the vaccine platform received, previous COVID-19 infection, and time since last antigen exposure. A follow-up study provided real-world evidence that pre-wave antibody titres were strongly associated with reduced COVID-19 incidence and severity of symptoms during the wave. Additionally, receiving a vaccine shot during the follow-up period significantly reduced the risk of COVID-19.
EPIDEMIOLOGY AND INFECTION
(2022)
Article
Oncology
Wojciech Kluzniak, Agata Szymiczek, Amelie Rodrigue, Dominika Wokolorczyk, Bogna Rusak, Klaudia Stempa, Tomasz Huzarski, Jacek Gronwald, Jan Lubinski, Neda Zamani, Shiyu Zhang, Jean-Yves Masson, Steven A. Narod, Cezary Cybulski, Mohammad R. Akbari
Summary: In the Polish population, the low-penetrance BRCA2 p.K3326* variant is associated with increased breast cancer risk only in individuals homozygous for the T allele of the ALDH2 rs10744777 variant, suggesting an interaction between these two variants.
JCO PRECISION ONCOLOGY
(2022)
