Article
Oncology
Mariateresa Casarotto, Valentina Lupato, Giorgio Giurato, Roberto Guerrieri, Sandro Sulfaro, Annamaria Salvati, Elisa D'Angelo, Carlo Furlan, Anna Menegaldo, Lorena Baboci, Barbara Montico, Irene Turturici, Riccardo Dolcetti, Salvatore Romeo, Vittorio Baggio, Stefania Corrado, Gianluca Businello, Maria Guido, Alessandro Weisz, Vittorio Giacomarra, Giovanni Franchin, Agostino Steffan, Luca Sigalotti, Emanuela Vaccher, Paolo Boscolo-Rizzo, Polesel Jerry, Giuseppe Fanetti, Elisabetta Fratta
Summary: This study evaluated the prognostic value of LINE-1 methylation level in oropharyngeal squamous cell carcinoma (OPSCC) patients. The results indicated that LINE-1 hypomethylation was associated with poor prognosis. The study also examined the relationship between LINE-1 methylation status and p53 protein expression as well as genome-wide/gene-specific DNA methylation.
CLINICAL EPIGENETICS
(2022)
Article
Endocrinology & Metabolism
Marco Capezzone, Alfonso Sagnella, Tania Pilli, Fabio Maino, Raffaella Forleo, Silvia Cantara, Alessandra Cartocci, Maria Grazia Castagna
Summary: Based on the study findings, age at diagnosis plays a significant role in determining the aggressiveness and prognosis of familial thyroid cancer when two family members are affected. Therefore, when defining familial cancer, the age at diagnosis of family members should be taken into consideration.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Article
Biochemistry & Molecular Biology
Mengyu Zhang, Weikang Sun, Xiaoxin You, Dongge Xu, Lingling Wang, Jingping Yang, Erguang Li, Susu He
Summary: This study analyzed publicly available datasets and found that EBV-associated gastric cancer (EBVaGC) has a repression of L1 transcription compared with EBV-negative gastric cancer (EBVnGC). Retrotransposition-associated young and full-length L1s (FL-L1s) were found to be the most repressed L1s in EBVaGC. Increased deposition of H3K9me3 on FL-L1s was observed, potentially attributed to increased TASOR expression and the interaction between viral DNA and the TASOR enhancer. This study uncovers a regulation mechanism of L1 expression by chromatin topology remodeling associated with viral-host genome interaction in EBVaGC.
NUCLEIC ACIDS RESEARCH
(2023)
Review
Cell Biology
Maria Daca Alvarez, Isabel Quintana, Mariona Terradas, Pilar Mur, Francesc Balaguer, Laura Valle
Summary: Early-onset colorectal cancer (EOCRC), diagnosed before age 50, comprises 10-12% of all new cases and its incidence is increasing. Approximately 13% of EOCRC patients carry pathogenic germline variants in known cancer predisposition genes, including 2.5% with germline pathogenic variants in hereditary cancer genes traditionally not associated with CRC predisposition. The high prevalence of hereditary cancer syndromes and familial history among EOCRC patients supports further research into the genetic background of this common disease.
Article
Genetics & Heredity
Timothy D. O'Brien, Amiee B. Potter, Catherine C. Driscoll, Gregory Goh, John H. Letaw, Sarah McCabe, Jane Thanner, Arpita Kulkarni, Rossana Wong, Samuel Medica, Tiana Week, Jacob Buitrago, Aaron Larson, Katie Johnson Camacho, Kim Brown, Rachel Crist, Casey Conrad, Sara Evans-Dutson, Ryan Lutz, Asia Mitchell, Pavana Anur, Vanessa Serrato, Autumn Shafer, Lisa K. Marriott, K. J. Hamman, Amelia Mulford, Wojciech Wiszniewski, Jone E. Sampson, Andrew Adey, Brian J. O'Roak, Christina A. Harrington, Jackilen Shannon, Paul T. Spellman, C. Sue Richards
Summary: The Healthy Oregon Project is a statewide initiative that aims to improve the health of Oregonians by providing no-cost genetic screening for inherited cancers and familial hypercholesterolemia. This unbiased population screening has successfully detected at-risk individuals who may have been missed by conventional medical approaches. The project has faced challenges in terms of developing a cost-effective test and scaling up the clinical laboratory to process a large number of samples.
AMERICAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Oncology
Nancy Porter, Daniel Laheru, Bryan Lau, Jin He, Lei Zheng, Amol Narang, Nicholas J. Roberts, Marcia Canto, Anne Marie Lennon, Michael G. Goggins, Ralph H. Hruban, Alison P. Klein
Summary: Individuals with a family history of pancreatic cancer, especially with multiple first-degree relatives affected, have a significantly increased risk of developing pancreatic cancer. The risk is also higher among individuals with a family history of young-onset pancreatic cancer.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2022)
Article
Multidisciplinary Sciences
Yanyang Zhao, Tian Yu, Jie Sun, Feiliang Wang, Chaoze Cheng, Shurong He, Lan Chen, Donghui Xie, Liping Fu, Xuhuizi Guan, An Yan, Yao Li, Gang Miao, Xiaoquan Zhu
Summary: The study identified WDR77 mutations associated with predisposition to nonsyndromic familial papillary thyroid cancer, where a rare heterozygous missense mutation in one family impairs the interaction of WDR77 with PRMT5, and a splice-site mutation in another family results in a marked decrease in H4R3me2 levels. These findings provide new insights into the genetic factors influencing thyroid cancer susceptibility.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Luis Crisostomo, Matthieu Bourgery, Luis Rato, Joao F. Raposo, Rachel L. Batterham, Noora Kotaja, Marco G. Alves
Summary: Excessive adiposity caused by high-fat diets may affect testicular metabolism and function in future generations through the influence of sperm small non-coding RNA.
Article
Multidisciplinary Sciences
Mohammed Dashti, Rasheeba Nizam, Prashantha Hebbar, Sindhu Jacob, Sumi Elsa John, Arshad Channanath, Hessa Al-Kandari, Thangavel Alphonse Thanaraj, Fahd Al-Mulla
Summary: This study identified differences in DNA methylation patterns between individuals with type 1 diabetes (T1D) and healthy individuals. Examining the genome-wide methylation of individuals from three Arab families, the study found that T1D-affected twins clustered together in terms of methylation patterns. The study also revealed 18 genes that were differentially methylated in T1D individuals compared to healthy individuals, and further validation confirmed the upregulation of ICA1 and DRAM1 genes in T1D samples.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Undraga Schagdarsurengin, Vanessa Breiding, Maria Loose, Florian Wagenlehner, Temuujin Dansranjav
Summary: The overexpression of IRAK1 in prostate cancer is associated with resistance to radiation-induced tumor cell death. The expression of IRAK1 is correlated with the methylation status of tumor cells, making it a potential predictive marker for selective IRAK1-targeting therapies.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Yoshifumi Baba, Noriko Yasuda, Miki Bundo, Yutaka Nakachi, Junko Ueda, Takatsugu Ishimoto, Masaaki Iwatsuki, Yuji Miyamoto, Naoya Yoshida, Hiroyuki Oshiumi, Kazuya Iwamoto, Hideo Baba
Summary: This study found that LINE-1 hypomethylation in upper GI cancers is associated with increased LINE-1 retrotransposition and tumor-specific insertion events, which may collectively contribute to the acquisition of aggressive tumor features through the inactivation of tumor-suppressive genes.
Article
Environmental Sciences
Zainab Awada, Liacine Bouaoun, Rihab Nasr, Arafat Tfayli, Cyrille Cuenin, Reem Akika, Rose-Mary Boustany, Joelle Makoukji, Hani Tamim, Nathalie K. Zgheib, Akram Ghantous
Summary: This pilot study found that blood LINE-1 methylation levels were significantly higher in breast cancer cases compared to controls in Lebanon, and LINE-1 hypo-methylation mediated 83% of the inverse effect of BMI on breast cancer risk. Further large-scale studies and stratification based on clinic-pathological types of breast cancer are warranted.
ENVIRONMENTAL RESEARCH
(2021)
Article
Medicine, General & Internal
Camilla Fontana, Federica Marasca, Livia Provitera, Sara Mancinelli, Nicola Pesenti, Shruti Sinha, Sofia Passera, Sergio Abrignani, Fabio Mosca, Simona Lodato, Beatrice Bodega, Monica Fumagalli
Summary: Premature infants show hypomethylation of L1 promoter at birth, and an early intervention program can restore normal methylation levels and improve neurodevelopment in children. Mouse study suggests fine-tuning of L1 activity in perinatal brain, indicating a sensitive and vulnerable window for L1 epigenetic setting.
Article
Biochemistry & Molecular Biology
Humberto Parada, Leili Sahrai, Mary S. Wolff, Regina M. Santella, Jia Chen, Alfred Neugut, Susan L. Teitelbaum
Summary: This study examined the interactions between parabens, global DNA methylation, and breast cancer risk. It found that exposure to parabens may increase the risk of breast cancer among women with hypomethylated global DNA methylation and tumors with gene-specific hypomethylated promoter regions.
MOLECULAR CARCINOGENESIS
(2022)
Article
Oncology
Dongli Liu, Luis Enriquez, Caroline E. Ford
Summary: This study investigated the role of the Wnt signalling receptor ROR2 in endometrial cancer and found that low expression was associated with unfavorable outcomes and reduced overall survival. Epigenetic repression of ROR2 expression was observed in cancer cell lines and patient samples, and ectopic expression inhibited invasive ability. The findings suggest that ROR2 may serve as a diagnostic or therapeutic candidate for endometrial cancer.
Article
Oncology
Leatrisse Oba, Ana F. Best, Phuong L. Mai, Maria Isabel Achatz, Paul S. Albert, Sharon A. Savage, Payal P. Khincha
Summary: Intermediate 4- and 8-monthly screening blood tests may not provide independent benefit for early cancer detection in Li-Fraumeni syndrome (LFS) patients, but annual comprehensive screening and personalized follow-up remain essential.
Article
Hematology
Marena R. Niewisch, Neelam Giri, Lisa J. McReynolds, Rotana Alsaggaf, Sonia Bhala, Blanche P. Alter, Sharon A. Savage
Summary: This study examined the associations between mode of inheritance in Dyskeratosis congenita related telomere biology disorders (DC/TBDs) and the clinical manifestations and long-term outcomes. The results showed that different modes of inheritance were correlated with different clinical presentations, and they also had an impact on the survival of patients.
Editorial Material
Hematology
Sharon A. Savage
Summary: In this study, novel pathogenic variants in RPA1 were discovered as a new cause of TBDs. The researchers investigated the clinical manifestations in patients from different families, and revealed the role of RPA1 in hematopoiesis and telomeric DNA binding and unfolding. The discovery enhances our understanding of RPA function in telomere biology and provides valuable information for families in understanding the cause of their illness.
Letter
Dermatology
Jessica N. Hatton, Michael R. Sargen, Megan N. Frone, Kelvin C. de Andrade, Sharon A. Savage, Payal P. Khincha
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Medicine, General & Internal
Mone't B. Thompson, Daniel Muldoon, Kelvin C. de Andrade, Neelam Giri, Blanche P. Alter, Sharon A. Savage, Robert D. Shamburek, Payal P. Khincha
Summary: The study found that oral androgen therapy in DC patients altered lipid and lipoprotein levels, potentially increasing the risk of atherogenic cardiovascular disease. Individuals on androgens for DC-related BMF should undergo cardiovascular disease monitoring.
Letter
Hematology
Esteban Arrieta-Bolanos, Pietro Crivello, Meilun He, Tao Wang, Shahinaz M. Gadalla, Sophie Paczesny, Steven G. E. Marsh, Stephanie J. Lee, Stephen R. Spellman, Yung-Tsi Bolon, Katharina Fleischhauer
Letter
Oncology
Ixtaccihuatl H. Obregon, Kelvin C. de Andrade, Renee C. Bremer, Payal P. Khincha, Sharon A. Savage
Article
Oncology
Pietro Crivello, Esteban Arrieta-Bolanos, Meilun He, Tao Wang, Stephanie Fingerson, Shahinaz M. Gadalla, Sophie Paczesny, Steven G. E. Marsh, Stephanie L. J. Lee, Stephen R. Spellman, Yung-Tsi Bolon, Katharina Fleischhauer
Summary: This study found that immunopeptidome divergence is a determinant of T-cell alloreactivity and clinical tolerability in single class I HLA-mismatched unrelated donor hematopoietic cell transplantation. Using hierarchical clustering of peptide-binding motifs, the authors classified 68.1% of the HLA-mismatched transplants as matched or mismatched. Mismatched transplants were associated with lower overall survival.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Hematology
Rohtesh S. Mehta, David Marin, Amin Alousi, Christopher G. Kanakry, Richard E. Champlin, Katayoun Rezvani, Elizabeth J. Shpall, Kristin Page, Shahinaz M. Gadalla, Daniel Weisdorf, Partow Kebriaei
Summary: In adult patients with acute lymphoblastic leukemia, younger haploidentical donors have better overall survival compared to older HLA-matched unrelated donors. Donor age is a prognostic factor for survival in hematopoietic cell transplantation.
Article
Primary Health Care
Jalen Brown, Ruth M. Pfeiffer, Duncan Shrewsbury, Stewart O'Callaghan, Alison M. Berner, Shahinaz M. Gadalla, Meredith S. Shiels, Sarah S. Jackson
Summary: This study found that transgender and gender diverse (TGD) individuals have a higher prevalence of cancer risk factors compared to cisgender individuals. Transmasculine individuals had higher rates of obesity and smoking, while transfeminine individuals had higher rates of dyslipidemia, diabetes, hepatitis C infection, hepatitis B infection, and HIV infection.
BRITISH JOURNAL OF GENERAL PRACTICE
(2023)
Article
Hematology
Hannah A. Raj, Tsung-Po Lai, Marena R. Niewisch, Neelam Giri, Youjin Wang, Stephen R. Spellman, Abraham Aviv, Shahinaz M. Gadalla, Sharon A. Savage
Summary: Individuals with telomere biology disorders (TBDs) have significantly shortened telomeres in blood cells, which is associated with increased risk of bone marrow failure and reduced survival. The mean telomere length is estimated to be 5 kilobases, but it is the shortest telomeres that indicate cellular senescence. By using the Telomere Shortest Length Assay (TeSLA), it was found that TBD patients have much shorter mean telomere length and an increased number of telomeres less than 3 kilobases. In addition, TBD patients with severe bone marrow failure and multiple organ manifestations have even shorter telomeres.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Editorial Material
Clinical Neurology
Shahinaz M. Gadalla, Mark H. Greene
Article
Multidisciplinary Sciences
Chiara Pederiva, Davide M. Trevisan, Dimitra Peirasmaki, Shan Chen, Sharon A. Savage, Ola Larsson, Jernej Ule, Laura Baranello, Federico Agostini, Marianne Farnebo
Summary: Posttranscriptional modifications of mRNA, including pseudouridylation, play a crucial role in gene expression regulation. In this study, dyskerin, a pseudouridine synthase, was found to bind to RNA polymerase II and be responsible for pseudouridylation of thousands of mRNAs. Dyskerin-mediated pseudouridylation was shown to interfere with translation and reduction of the modification led to enhanced protein synthesis. Furthermore, dyskeratosis congenita patients with mutations in the dyskerin-encoding gene showed severe reduction in mRNA pseudouridylation.
Review
Geriatrics & Gerontology
Sharon A. Savage
Summary: Telomere length is crucial in genomic stability and cancer risk, with both too short and too long telomeres associated with increased cancer risks.