Article
Oncology
Jihoon E. Joo, Khalid Mahmood, Romy Walker, Peter Georgeson, Ida Candiloro, Mark Clendenning, Julia Como, Sharelle Joseland, Susan Preston, Lise Graversen, Mathilda Wilding, Michael Field, Michelle Lemon, Janette Wakeling, Helen Marfan, Rachel Susman, Joanne Isbister, Emma Edwards, Michelle Bowman, Judy Kirk, Emilia Ip, Lynne McKay, Yoland Antill, John L. Hopper, Alex Boussioutas, Finlay A. Macrae, Alexander Dobrovic, Mark A. Jenkins, Christophe Rosty, Ingrid M. Winship, Daniel D. Buchanan
Summary: MLH1 epimutation can cause colorectal cancer, and it can be classified into germline MLH1 promoter variants and MLH1 methylated early-onset CRCs based on tumour molecular profiles. Genome-wide DNA methylation and somatic mutational profiles were compared between different types of MLH1 epimutation CRCs and reference CRCs. Mosaic MLH1 methylation can be detected in blood, normal mucosa, and buccal DNA using methylation-sensitive ddPCR.
CLINICAL EPIGENETICS
(2023)
Article
Genetics & Heredity
Ileana Wanda Carnevali, Giulia Cini, Laura Libera, Nora Sahnane, Sofia Facchi, Alessandra Viel, Fausto Sessa, Maria Grazia Tibiletti, Paolo Cinelli
Summary: MLH1 hypermethylation is not exclusively a sporadic cancer mechanism, as a significant number of LS-related cancers also exhibit MLH1 hypermethylation. Current flow charts for universal LS screening should include MLH1 methylation to be applied, taking into account a patient's family and personal history.
Article
Oncology
Annukka Pasanen, Mikko Loukovaara, Elina Kaikkonen, Alisa Olkinuora, Kirsi Pylvaenaeinen, Pia Alhopuro, Paeivi Peltomaeki, Jukka-Pekka Mecklin, Ralf Buetzow
Summary: International guidelines recommend universal screening of endometrial carcinoma patients for Lynch syndrome. This study found that limiting methylation testing to patients under 65 years would reduce the testing effort while maintaining a low false negative rate.
Article
Oncology
Takashi Kawai, Akihiro Nyuya, Yoshiko Mori, Takehiro Tanaka, Hiroaki Tanioka, Kazuya Yasui, Toshiaki Toshima, Fumitaka Taniguchi, Kunitoshi Shigeyasu, Yuzo Umeda, Toshiyoshi Fujiwara, Makoto Okawaki, Yoshiyuki Yamaguchi, Ajay Goel, Takeshi Nagasaka
Summary: Mutation in the POLE gene is rare in CRC patients, occurring in younger individuals and usually in the right colon. These patients are diagnosed at an early stage, and distinct epigenetic alterations may be associated with CD8 cell infiltration.
CLINICAL EPIGENETICS
(2021)
Article
Genetics & Heredity
Oleksii Nikolaienko, Hans P. Eikesdal, Elisabet Ognedal, Bjornar Gilje, Steinar Lundgren, Egil S. Blix, Helge Espelid, Jurgen Geisler, Stephanie Geisler, Emiel A. M. Janssen, Synnove Yndestad, Laura Minsaas, Beryl Leirvaag, Reidun Lillestol, Stian Knappskog, Per E. Lonning
Summary: This study found that approximately 20% of TNBC and low-ER expression breast cancers may be caused by prenatal BRCA1 epimutations. The constitutional mosaic BRCA1 methylation likely arises through gender-related mechanisms in utero, independent of Mendelian inheritance.
Article
Oncology
Yoland Antill, Daniel D. Buchanan, Clare L. Scott
Summary: Endometrial cancer patients with Lynch gene or POLE/POLD1 gene mutations are more likely to respond well to immune therapy, while those with silencing of the MLH1 gene may not be as responsive. Combination therapies may be important to consider for these patients.
Article
Pathology
Miralem Mrkonjic, Gulisa Turashvili
Summary: This study assessed the use of EPM2AIP1 immunohistochemical (IHC) testing in combination with MMR proteins as a surrogate marker for MLH1 promoter methylation status. The results showed that EMP2AIP1 IHC correlated well with MLH1 promoter methylation results, suggesting its potential as an alternative method for methylation testing.
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
(2022)
Article
Oncology
Karolin Bucksch, Silke Zachariae, Aysel Ahadova, Stefan Aretz, Reinhard Buttner, Heike Goergens, Elke Holinski-Feder, Robert Hueneburg, Matthias Kloor, Magnus Knebel Doeberitz, Swetlana Ladigan-Badura, Gabriela Moeslein, Monika Morak, Jacob Nattermann, Huu Phuc Nguyen, Claudia Perne, Silke Redler, Ariane Schmetz, Verena Steinke-Lange, Harald Surowy, Deepak B. Vangala, Juergen Weitz, Markus Loeffler, Christoph Engel
Summary: This study aimed to characterize and compare the risks for adenoma and CRC in Lynch syndrome (LS), Lynch-like syndrome (LLS) and familial colorectal cancer type X (FCCX). The study found similar risks for colorectal adenomas, but different risks for first and metachronous CRC between the three risk groups, with CRC risk highest in LS, followed by LLS and lowest in FCCX. Male sex and a prevalent adenoma in the index colonoscopy were associated with a higher risk for incident adenoma and CRC.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Article
Pathology
Sara Iolanda Oliveira da Silva, Tabata Alves Domingos, Bruna Elisa Catin Kupper, Louise De Brot, Samuel Aguiar Junior, Dirce Maria Carraro, Giovana Tardin Torrezan
Summary: We developed a test for assessing MLH1 promoter methylation based on NGS and evaluated its concordance with BRAF mutation status in CRC. Our results showed a high concordance between MLH1 methylation and BRAF mutation in MLH1/PMS2 deficient tumors, indicating that this NGS test could be used to identify sporadic causes of MLH1/PMS2 deficiency in CRC.
EXPERIMENTAL AND MOLECULAR PATHOLOGY
(2023)
Article
Oncology
Luigi Corsaro, Vincenzo Sandro Gambino
Summary: Oestrogen receptor expression in breast cancer cells is a marker for high cellular differentiation and can be used to identify two distinct breast cancer groups (ER-positive and ER-negative) with differences in biological characteristics, clinical behavior, and therapeutic options. This study used epigenetic wide association study datasets to compare these two breast cancer groups using an epimutation score. Functional and pathway enrichment analyses revealed common genetic pathways associated with higher and significant epimutation scores in ER-positive breast cancer, including the SUMOylation, Notch, IFN-γ signaling, and deubiquitination protease pathways. On the other hand, ER-positive breast cancer was also associated with a higher and significant level of epimutation due to hypomethylation in genes belonging to the ESR-mediated pathway, consistent with an active estrogen-mediated signaling pathway in this group.
Article
Oncology
Daniele Fanale, Lidia Rita Corsini, Chiara Brando, Alessandra Dimino, Clarissa Filorizzo, Luigi Magrin, Roberta Sciacchitano, Alessia Fiorino, Tancredi Didier Bazan Russo, Valentina Calo, Juan Lucio Iovanna, Edoardo Francini, Antonio Russo, Viviana Bazan
Summary: Lynch syndrome is a genetic condition associated with an increased predisposition to colorectal cancer and other tumors. The most efficient strategy to identify patients with this syndrome is still unclear. A study found that analyzing tissue microsatellite instability according to the revised Bethesda guidelines is the best selection approach, but using different selection methods as complementary strategies helps reduce underdiagnosis.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Ellis L. Eikenboom, Saskia M. Wilting, Teoman Deger, Malgorzata I. Srebniak, Monique Van Veghel-Plandsoen, Ruben G. Boers, Joachim B. Boers, Wilfred F. J. van IJcken, Joost H. Gribnau, Peggy Atmodimedjo, Hendrikus J. Dubbink, John W. M. Martens, Manon C. W. Spaander, Anja Wagner
Summary: We assessed which ctDNA assay might be most suitable for a ctDNA-based CRC screening/surveillance blood test. The results showed that cfDNA methylation profiles could discriminate all microsatellite instable advanced neoplasia, making it a particularly promising tool for Lynch syndrome surveillance. Larger studies are needed to validate these findings.
Article
Biochemistry & Molecular Biology
Vitaly Shubin, Yury Shelygin, Sergey Achkasov, Oleg Sushkov, Ilya Nazarov, Alexey Ponomarenko, Iuliia Alimova, Anna Loginova, Aleksey Tsukanov
Summary: The aim of this study was to determine the characteristics of Russian patients with microsatellite instability (MSI) tumors. The results showed that patients with MSI tumors differed in the age of diagnosis, tumor localization, time of cancer recurrence, and stage of the disease. Patients whose tumors had MSI status had higher overall and disease-free survival rates.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Julie Leclerc, Catherine Vermaut, Marie-Pierre Buisine
Summary: Microsatellite instability (MSI) is a hallmark of Lynch syndrome (LS)-related tumors, but it is not exclusive to LS, as most MSI/mismatch repair-deficient (dMMR) tumors are sporadic. Advances in diagnostic and screening strategies have evolved in recent years, focusing on identifying LS patients and distinguishing LS-related from sporadic MSI tumors. Discussions on pitfalls associated with current strategies aim to improve LS diagnosis and prevent inappropriate clinical management.
Article
Oncology
Anna Plotkin, Ekaterina Olkhov-Mitsel, Sharon Nofech-Mozes
Summary: MLH1 promoter hypermethylation is a common cause of mismatch repair deficiency in endometrial cancer. This study examined the proportion of MLH1-deficient endometrial cancer cases with hypermethylation, assessed the impact of reflex MLH1-PHM testing strategy, and evaluated the associated costs. The results showed that MLH1 hypermethylation is prevalent in endometrial cancer and reflex testing incurs substantial costs. The study suggests the need to optimize resource utilization and testing approaches in healthcare systems with finite resources.
Article
Substance Abuse
Nicola R. Jones, Matthew Hickman, Sarah Larney, Suzanne Nielsen, Robert Ali, Thomas Murphy, Timothy Dobbins, David A. Fiellin, Louisa Degenhardt
Summary: The study found that hospital stays due to NFOD are relatively common among opioid-dependent individuals, with higher incidence rates in women and younger age groups. Rates of NFOD and substances involved vary by sex, age, and over time, highlighting the need for widespread interventions to prevent overdose in this population.
DRUG AND ALCOHOL DEPENDENCE
(2021)
Article
Medicine, General & Internal
Louisa Degenhardt, Phillip Hungerford, Suzanne Nielsen, Raimondo Bruno, Briony Larance, Philip J. Clare, Timothy Dobbins, Wayne Hall, Milton Cohen, Fiona Blyth, Nicholas Lintzeris, Michael Farrell, Gabrielle Campbell
Summary: The study examined opioid behaviors and indicators of extramedical use and harm in individuals prescribed opioids for chronic noncancer pain. Findings showed significant variability in opioid use behaviors, extramedical behaviors, and opioid dependence, highlighting the importance of reevaluating the effectiveness and safety of prescription opioid use over time.
Article
Substance Abuse
Alison Ritter, Katinka van de Ven, Thu Vuong, Jenny Chalmers, Timothy Dobbins, Michael Livingston, Lynda Berends
Summary: This study found no significant associations between procurement and funding contract arrangements and client outcomes for alcohol and drug treatment services. However, treatment length of stay may be associated with AOD workforce and case-loads, while receiving services from a government provider may be associated with lower treatment completion rates.
Article
Substance Abuse
Chrianna Bharat, Louisa Degenhardt, Timothy Dobbins, Sarah Larney, Michael Farrell, Sebastiano Barbieri
Summary: The study found that there was no significant difference in performance between traditional Cox regression and deep learning models in predicting individuals' time in opioid agonist treatment. Deep learning may be more useful in identifying novel risk factors for treatment retention from administrative data.
DRUG AND ALCOHOL DEPENDENCE
(2021)
Article
Cardiac & Cardiovascular Systems
Aditya Bhat, Gary C. H. Gan, Henry H. L. Chen, Shaun Khanna, Sumreen Nawaz, Maria Carmo P. Nunes, Timothy Dobbins, C. Raina MacIntyre, Timothy C. Tan
Summary: Left atrial enlargement and reduced LA mechanical function, reflected through LA volume index and LA emptying fraction, are associated with AF rehospitalization and long-term adverse cardiovascular outcomes in patients with nonvalvular AF following index hospitalization.
JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY
(2021)
Article
Genetics & Heredity
Miranda E. Vidgen, Dayna Williamson, Katrina Cutler, Claire McCafferty, Robyn L. Ward, Keith McNeil, Nicola Waddell, David Bunker
Summary: The implementation of genomics in healthcare systems presents challenges which can be addressed by drawing lessons from other programs. An adaptive approach allows for flexibility to respond to learnings and external factors. Challenges include engagement of people and services, and the design of individual projects and the overall program.
NPJ GENOMIC MEDICINE
(2021)
Article
Substance Abuse
Monika Dzidowska, K. S. Kylie Lee, James H. Conigrave, Timothy A. Dobbins, Beth Hummerston, Scott Wilson, Paul S. Haber, Dennis Gray, Katherine M. Conigrave
Summary: This study demonstrates that an early support model can increase alcohol screening rates in Aboriginal health services. However, the impact on treatment outcomes is less clear.
Article
Genetics & Heredity
Sarah Norris, Andrea Belcher, Kirsten Howard, Robyn L. Ward
Summary: MSAC is an independent committee established by the Australian government to provide recommendations on public reimbursement of non-pharmaceutical technologies and services. Their recent publication on clinical utility cards for genetic testing identified methodological and policy challenges, including how to incorporate patient and societal preferences for genomic testing outcomes in global health technology assessments.
JOURNAL OF COMMUNITY GENETICS
(2022)
Article
Substance Abuse
Janni Leung, Vivian Chiu, Nicola Man, Wing See Yuen, Timothy Dobbins, Adrian Dunlop, Natasa Gisev, Wayne Hall, Sarah Larney, Sallie-Anne Pearson, Louisa Degenhardt, Amy Peacock
Summary: In New South Wales, Australia, individuals who had an alcohol-related hospital inpatient or emergency department presentation between 2005 and 2014 had a higher risk of mortality than the general population during the same period.
Article
Immunology
Jonathan M. King, Kathy Petoumenos, Timothy Dobbins, Rebecca J. Guy, Richard T. Gray, Steven J. Nigro, Damin Si, Byron Minas, Skye McGregor
Summary: Australia aims to eliminate HIV transmission by the end of 2022, but there is a lack of accurate information on HIV transmission among residents. The researchers developed a method to estimate the timing of HIV acquisition among migrants to Australia. They found that almost half of migrants diagnosed with HIV acquired the infection after arrival in Australia, underscoring the need for tailored testing and prevention programs.
JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
(2023)
Article
Substance Abuse
Andrea L. Schaffer, Natasa Gisev, Fiona M. Blyth, Nicholas A. Buckley, David Currow, Timothy A. Dobbins, Andrew Wilson, Louisa Degenhardt, Sallie-Anne Pearson
Summary: We analyzed opioid prescribing patterns among medical practitioners in New South Wales, Australia from 2013 to 2018. Our findings revealed substantial variations in opioid prescribing, which were clustered into four general patterns. Some prescribing patterns were concerning and may potentially harm patients. These findings provide insights for targeted interventions to address potentially harmful practices.
DRUG AND ALCOHOL REVIEW
(2023)
Article
Substance Abuse
James H. Conigrave, Emma K. Devine, K. S. Kylie Lee, Timothy Dobbins, Julia Vnuk, Noel Hayman, Katherine Conigrave
Summary: This study explored the impact of COVID-19 lockdowns on the rate of screening for risky drinking in Aboriginal Community Controlled Health Services in Australia. The findings suggest that the screening rate significantly decreased in urban and inner regional areas during the lockdowns, while there was no significant change in other regions. As harm from alcohol consumption may have increased during the lockdowns, policymakers should consider ways to continue screening for risky drinking during future lockdowns.
DRUG AND ALCOHOL REVIEW
(2023)
Meeting Abstract
Public, Environmental & Occupational Health
Natasa Gisev, Sallie-Anne Pearson, Timothy Dobbins, Luke Buizen, Tom Murphy, Andrew Wilson, Fiona Blyth, Adrian Dunlop, Sarah Larney, David Currow, Richard Mattick, Louisa Degenhardt
PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
(2021)
Meeting Abstract
Public, Environmental & Occupational Health
Chrianna Bharat, Sarah Larney, Sebastiano Barbieri, Timothy Dobbins, Nicola R. Jones, Matthew Hickman, Natasa Gisev, Robert Ali, Louisa Degenhardt
PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
(2021)
Article
Health Care Sciences & Services
Bette Liu, Duleepa Jayasundara, Victoria Pye, Timothy Dobbins, Gregory J. Dore, Gail Matthews, John Kaldor, Paula Spokes
Summary: The study found that 80% of COVID-19 patients recover within a month, but about 5% continue to experience symptoms 3 months later. Factors such as age, gender, and pre-existing conditions influence the recovery time of patients.
LANCET REGIONAL HEALTH-WESTERN PACIFIC
(2021)
Article
Genetics & Heredity
Katerina S. Kucera, Beth Lincoln Boyea, Brooke Migliore, Sarah Nelson Potter, Veronica R. Robles, Oksana Kutsa, Heidi Cope, Katherine C. Okoniewski, Anne Wheeler, Catherine W. Rehder, Edward C. Smith, Holly L. Peay
Summary: Screening for elevated CK-MM levels in dried blood spots is a feasible method to identify newborns with DMD. Including specific cutoffs, repeat testing, and genetic sequencing can improve the accuracy and sensitivity of screening.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Madeline Currey, Ilana Solomon, Sarah Mcgraw, Jenny Shen, Francisco Munoz, Ernesto Sosa, Vanessa Puello-Lozano, Sam Wing, Lisa Lopez, Michelle Afkhami, Janine Lobello, Szabolcs Szelinger, Stacy W. Gray
Summary: This study conducted qualitative interviews with cancer patients and providers to identify gaps in clinical care and propose care delivery solutions for the return of secondary germline findings. The responses of patients varied depending on the amount of pre-test counseling they received, and providers identified insufficient clinic time as a major barrier to pretest education. Online support tools and standardized pre-test education models were favored by providers. There were differing perspectives on how pre-test education should be integrated into clinical workflows, but agreement on the inclusion of differences between somatic and germline testing, likelihood of medically actionable findings, and the possibility of being referred to a genetics provider.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Kiely N. James, Shimul Chowdhury, Yan Ding, Sergey Batalov, Kelly Watkins, Yong Hyun Kwon, Lucitia Van Der Kraan, Katarzyna Ellsworth, Stephen F. Kingsmore, Lucia Guidugli
Summary: This study used genome sequencing to detect a wide range of copy-number variants (CNVs) and other non-single nucleotide variant/indel variant types. These genetic alterations accounted for 15.8% of reported variants, with deletions being the most common type. The study also found that additional genetic tests were ordered in some cases, but failed to report the variants detected by genome sequencing.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Asem Berkalieva, Nicole R. Kelly, Ashley Fisher, Samuel F. Hohmann, Monisha Sebastin, Miranda Di Biase, Katherine E. Bonini, Priya Marathe, Jacqueline A. Odgis, Sabrina A. Suckiel, Michelle A. Ramos, Rosamond Rhodes, Noura S. Abul-Husn, John M. Greally, Carol R. Horowitz, Melissa P. Wasserstein, Eimear E. Kenny, Bruce D. Gelb, Bart S. Ferket
Summary: The study aims to understand the effects of returning diagnostic sequencing results on clinical actions and economic outcomes for pediatric patients with suspected genetic disorders. The results showed that patients with positive findings were more likely to receive specialist consultation, but there were no significant increases in overall physician services and costs. More large-scale studies are needed to confirm these findings.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Kirstine Stochholm, Camilla Holmgard, Shanlee M. Davis, Claus H. Gravholt, Agnethe Berglund
Summary: This study assessed the incidence, prevalence, and age at diagnosis of individuals with 45,X/46,XY mosaicism and described the associated mortality pattern. The study found an increasing incidence of 45,X/46,XY mosaicism in males and a stable incidence in females. Males were diagnosed at an older age than females. Additionally, 45,X/46,XY mosaicism was associated with increased all-cause mortality.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Yunjia Chen, Ender Karaca, Nathaniel H. Robin, Dana Goodloe, Ali Al-Beshri, S. Joy Dean, Anna C. E. Hurst, Andrew J. Carroll, Fady M. Mikhail
Summary: This study confirms the association between DLG2 intragenic deletions and neurodevelopmental disorders, supports the haploinsufficiency of the DLG2 gene, and suggests a potential association between these deletions and congenital anomalies and dysmorphism.
GENETICS IN MEDICINE
(2024)
