763 results on '"Kench A"'
Search Results
2. Dimeric Metal-Salphen Complexes Which Target Multimeric G-Quadruplex DNA
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Timothy Kench, Viktoria Rakers, David Bouzada, Jacobo Gomez-González, Jenna Robinson, Marina K. Kuimova, Miguel Vázquez López, M. Eugenio Vázquez, and Ramon Vilar
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Pharmacology ,Organic Chemistry ,Biomedical Engineering ,Pharmaceutical Science ,Bioengineering ,Biotechnology - Published
- 2023
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3. Can simulation-based education or other education interventions replace clinical placement in medical radiation sciences? A narrative review
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Y.A. Jimenez, F. Gray, L. Di Michele, S. Said, W. Reed, and P. Kench
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Radiology, Nuclear Medicine and imaging ,Podiatry - Published
- 2023
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4. Artefact removal from micrographs with deep learning based inpainting
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Isaac Squires, Amir Dahari, Samuel J. Cooper, and Steve Kench
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Imaging is critical to the characterisation of materials. However, even with careful sample preparation and microscope calibration, imaging techniques can contain defects and unwanted artefacts. This is particularly problematic for applications where the micrograph is to be used for simulation or feature analysis, as artefacts are likely to lead to inaccurate results. Microstructural inpainting is a method to alleviate this problem by replacing artefacts with synthetic microstructure with matching boundaries. In this paper we introduce two methods that use generative adversarial networks to generate contiguous inpainted regions of arbitrary shape and size by learning the microstructural distribution from the unoccluded data. We find that one benefits from high speed and simplicity, whilst the other gives smoother boundaries at the inpainting border. We also describe an open-access graphical user interface that allows users to utilise these machine learning methods in a ‘no-code’ environment.
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- 2023
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5. Machine-Learning-Driven Advanced Characterization of Battery Electrodes
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Donal P. Finegan, Isaac Squires, Amir Dahari, Steve Kench, Katherine L. Jungjohann, and Samuel J. Cooper
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Fuel Technology ,Renewable Energy, Sustainability and the Environment ,Chemistry (miscellaneous) ,Materials Chemistry ,Energy Engineering and Power Technology - Abstract
Materials characterization is fundamental to our understanding of lithium ion battery electrodes and their performance limitations. Advances in laboratory-based characterization techniques have yielded powerful insights into the structure–function relationship of electrodes, yet there is still far to go. Further improvements rely, in part, on gaining a deeper understanding of complex physical heterogeneities in the materials. However, practical limitations in characterization techniques inhibit our ability to combine data directly. For example, some characterization techniques are destructive, thus preventing additional analyses on the same region. Fortunately, artificial intelligence (AI) has shown great potential for achieving representative, 3D, multi-modal datasets by leveraging data collected from a range of techniques. In this Perspective, we give an overview of recent advances in lab-based characterization techniques for Li-ion electrodes. We then discuss how AI methods can combine and enhance these techniques, leading to substantial acceleration in our understanding of electrodes.
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- 2022
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6. African-specific molecular taxonomy of prostate cancer
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Weerachai Jaratlerdsiri, Jue Jiang, Tingting Gong, Sean M. Patrick, Cali Willet, Tracy Chew, Ruth J. Lyons, Anne-Maree Haynes, Gabriela Pasqualim, Melanie Louw, James G. Kench, Raymond Campbell, Lisa G. Horvath, Eva K. F. Chan, David C. Wedge, Rosemarie Sadsad, Ilma Simoni Brum, Shingai B. A. Mutambirwa, Phillip D. Stricker, M. S. Riana Bornman, and Vanessa M. Hayes
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Male ,China ,Multidisciplinary ,Black People ,Nuclear Proteins ,Prostatic Neoplasms ,Europe ,Nuclear Receptor Coactivator 2 ,Asian People ,Africa ,Mutation ,Ethnicity ,Humans ,RNA, Long Noncoding ,Carrier Proteins ,Africa South of the Sahara ,RNA Helicases - Abstract
Prostate cancer is characterized by considerable geo-ethnic disparity. African ancestry is a significant risk factor, with mortality rates across sub-Saharan Africa of 2.7-fold higher than global averages1. The contributing genetic and non-genetic factors, and associated mutational processes, are unknown2,3. Here, through whole-genome sequencing of treatment-naive prostate cancer samples from 183 ancestrally (African versus European) and globally distinct patients, we generate a large cancer genomics resource for sub-Saharan Africa, identifying around 2 million somatic variants. Significant African-ancestry-specific findings include an elevated tumour mutational burden, increased percentage of genome alteration, a greater number of predicted damaging mutations and a higher total of mutational signatures, and the driver genes NCOA2, STK19, DDX11L1, PCAT1 and SETBP1. Examining all somatic mutational types, we describe a molecular taxonomy for prostate cancer differentiated by ancestry and defined as global mutational subtypes (GMS). By further including Chinese Asian data, we confirm that GMS-B (copy-number gain) and GMS-D (mutationally noisy) are specific to African populations, GMS-A (mutationally quiet) is universal (all ethnicities) and the African–European-restricted subtype GMS-C (copy-number losses) predicts poor clinical outcomes. In addition to the clinical benefit of including individuals of African ancestry, our GMS subtypes reveal different evolutionary trajectories and mutational processes suggesting that both common genetic and environmental factors contribute to the disparity between ethnicities. Analogous to gene–environment interaction—defined here as a different effect of an environmental surrounding in people with different ancestries or vice versa—we anticipate that GMS subtypes act as a proxy for intrinsic and extrinsic mutational processes in cancers, promoting global inclusion in landmark studies.
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- 2022
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7. Patient requests for radiological services: An Australian study of patient agency and the impact of online health information
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Lizzie De Silva, Melissa Baysari, Melanie Keep, Peter Kench, and Jillian Clarke
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Community and Home Care ,Public Health, Environmental and Occupational Health - Abstract
The Internet has been instrumental in patients' knowledge about health and medicine through increasing consultation of online sources that advocate self-management. For example, those patients who request referrals from their doctors for tests and procedures in radiology. Such patient-initiated referral requests can devolutionise the traditional model of health care. This study aimed to understand individuals who sought online health information (OHI) and whether requests for radiological referrals were the result of OHI seeking.The individuals targeted were those who have had a radiological procedure in the past 5 years. Using an online survey tool, individuals completed a 20-min anonymous survey. Included in the survey was a validated digital health literacy measurement scale, eHEALS.Those who scored higher on the eHEALS measure were likely to be under 55 years of age and were more inclined to request radiological referrals. Though they were not concerned with the credibility of sourced websites, most secured the desired outcome from their requests.Overall, this study indicates that patients are consulting online sites for health information, and individuals with higher digital literacy scores are asking doctors for referrals for radiological tests and procedures. These findings confirm our anecdotal experience in radiology departments. So what?: In conducting this study, we hope to better inform radiology and other health practitioners of the way OHI is impacting clinical practice.
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- 2022
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8. <scp>Long‐term</scp> normothermic perfusion of human livers for longer than 12 days
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Ngee‐Soon Lau, Mark Ly, Claude Dennis, Ken Liu, James Kench, Michael Crawford, and Carlo Pulitano
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Biomaterials ,Biomedical Engineering ,Medicine (miscellaneous) ,Bioengineering ,General Medicine - Published
- 2022
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9. The potential advantages and workflow challenges of long axial field of view <scp>PET</scp> / <scp>CT</scp>
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Wei‐Ting J. Chen, William I. D. Rae, Peter L. Kench, and Steven R. Meikle
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Radiological and Ultrasound Technology ,Radiology, Nuclear Medicine and imaging - Published
- 2023
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10. Fossil Java Sea corals record Laurentide ice sheet disappearance
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Mann, T., Schöne, T., Kench, P., Lambeck, K., Ashe, E., Kneer, D., Beetham, E., Illigner, J., Rovere, A., Marfai, M., and Westphal, H.
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Settore GEO/04 - Geografia Fisica e Geomorfologia ,Geology - Abstract
The Laurentide ice sheet was the largest late Pleistocene ice mass and the largest contributor to Holocene pre-industrial sea-level rise. While glaciological dates suggest final ice sheet melting between 8 and 6 ka, inversion of sea-level data indicates deglaciation at ca. 7 ka. Here, we present new chronostratigraphic constraints on Laurentide ice sheet disappearance based on Holocene relative sea-level observations from the tectonically stable north coast of Java, Indonesia. Age-elevation data from the flat upper surfaces of 13 fossil intertidal corals (i.e., microatolls) indicate that the Java Sea experienced a relative sea level of 1.3 ± 0.7 m above present between 6.9 and 5.3 ka. To determine uncaptured relative sea-level trends within the observational uncertainties of this apparently constant highstand, we analyzed the internal structure of three sliced microatolls from the same site to produce a high-resolution data set. These data were used to statistically model relative sea-level rates and trends. Employing the data with the model provided evidence for a short-lived rise of relative sea level from 1.0 ± 0.3 m above present at 6.7 ± 0.1 ka to 1.9 ± 0.3 m above present at 6.4 ± 0.1 ka. The end of this rise likely represents the last input of meltwater from the vast Laurentide ice sheet, which, consequently, collapsed at least 400 yr later than assumed by some widely used models of glacial isostatic adjustment. Incorporating these new results into such predictive models will help to better understand the geographical variability of future sea-level rise as a result of global warming.
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- 2023
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11. Sensitivity of virtual non-contrast dual-energy CT urogram for detection of urinary calculi: a systematic review and meta-analysis
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Katherine McCoombe, Karen Dobeli, Steven Meikle, Stacey Llewellyn, and Peter Kench
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Furosemide ,Humans ,Urography ,Urinary Calculi ,Radiology, Nuclear Medicine and imaging ,General Medicine ,Tomography, X-Ray Computed ,Sensitivity and Specificity - Abstract
Objective To determine the sensitivity of dual-energy (DE) virtual non-contrast computed tomography (vNCT), generated from the excretory phase of a CT urogram, compared to true non-contrast CT (tNCT) for the detection of urinary calculi. Methods A search of multiple medical literature databases was performed using predetermined search terms. Inclusion and exclusion criteria were applied, and bias risk was assessed by two independent reviewers using the quality assessment of diagnostic accuracy studies (QUADAS) tool. Collated estimates of sensitivity were generated, and sources of heterogeneity were identified and reviewed. Results Thirteen studies (1760 patients; 1740 urinary calculi) were included for sensitivity assessment. Pooled sensitivity for urinary calculi on vNCT was 78.1% (95% CI: 70.2 to 85.0%); however, heterogeneity between studies was very high (I2 = 92.0%). Sources of heterogeneity between studies were explored through subgroup analysis by categorising studies according to slice thickness (≥ 2 mm and < 2 mm), use of oral hydration, and use of intravenous furosemide. Pooled sensitivity for detection of urinary calculi on vNCT for studies that used oral hydration and < 2 mm slice thickness was 92.2% (95% CI: 89.5 to 94.5%). Pooled specificity was not performed as true negatives were not reported in most studies. Potential sources of bias were identified in included studies. Conclusion vNCT demonstrated a moderate pooled sensitivity compared to tNCT for the detection of urinary calculi in split bolus CT urogram protocols. However, subgroup analysis suggests higher sensitivity when employing oral hydration and < 2 mm slice thickness or increment. Key Points • vNCT demonstrated moderate pooled sensitivity for the detection of urinary calculi in split bolus CT urogram protocols. • Subgroup analysis suggested higher sensitivity with oral hydration and < 2 mm slice thickness or increment.
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- 2022
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12. Supplementary Figure 2 from Epigenetic Deregulation Across Chromosome 2q14.2 Differentiates Normal from Prostate Cancer and Provides a Regional Panel of Novel DNA Methylation Cancer Biomarkers
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Susan J. Clark, Robert L. Sutherland, Miguel A. Peinado, Regina Mayor, Anne-Maree Haynes, Ruth Pe Benito, Susan M. Henshall, James G. Kench, Toby Hulf, Marcel W. Coolen, Bruce Tabor, Lisa G. Horvath, Kate I. Patterson, Aaron L. Statham, Jenny Z. Song, Wenjia Qu, Clare Stirzaker, and James Devaney
- Abstract
Supplementary Figure 2 from Epigenetic Deregulation Across Chromosome 2q14.2 Differentiates Normal from Prostate Cancer and Provides a Regional Panel of Novel DNA Methylation Cancer Biomarkers
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- 2023
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13. Supplementary Table 2 from Comparative Biomarker Expression and RNA Integrity in Biospecimens Derived from Radical Retropubic and Robot-Assisted Laparoscopic Prostatectomies
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David J. Horsfall, Wayne D. Tilley, Robert L. Sutherland, Gail P. Risbridger, Judith A. Clements, Hong Wang, Ying Dong, James G. Kench, Hemamali Samaratunga, Peter D. Sutherland, Villis R. Marshall, Penelope A. Cohen, Thomas J. Dodd, Shalini Jindal, Tina Bianco-Miotto, and Carmela Ricciardelli
- Abstract
Supplementary Table 2 from Comparative Biomarker Expression and RNA Integrity in Biospecimens Derived from Radical Retropubic and Robot-Assisted Laparoscopic Prostatectomies
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- 2023
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14. Supplementary Figure Legend from Global Levels of Specific Histone Modifications and an Epigenetic Gene Signature Predict Prostate Cancer Progression and Development
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Carmela Ricciardelli, David J. Horsfall, Wayne D. Tilley, Lisa M. Butler, Judith A. Clements, Gail P. Risbridger, Howard I. Scher, William L. Gerald, Susan M. Henshall, Robert L. Sutherland, Villis R. Marshall, Phillip D. Stricker, James G. Kench, Lisa G. Horvath, Wendy A. Raymond, Natalie K. Ryan, Melissa A. O'Loughlin, Marie A. Pickering, Mervyn Thomas, Tanya K. Day, Shalini Jindal, Grant Buchanan, Karen Chiam, and Tina Bianco-Miotto
- Abstract
Supplementary Figure Legend from Global Levels of Specific Histone Modifications and an Epigenetic Gene Signature Predict Prostate Cancer Progression and Development
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- 2023
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15. Supplementary Table 1 from Global Levels of Specific Histone Modifications and an Epigenetic Gene Signature Predict Prostate Cancer Progression and Development
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Carmela Ricciardelli, David J. Horsfall, Wayne D. Tilley, Lisa M. Butler, Judith A. Clements, Gail P. Risbridger, Howard I. Scher, William L. Gerald, Susan M. Henshall, Robert L. Sutherland, Villis R. Marshall, Phillip D. Stricker, James G. Kench, Lisa G. Horvath, Wendy A. Raymond, Natalie K. Ryan, Melissa A. O'Loughlin, Marie A. Pickering, Mervyn Thomas, Tanya K. Day, Shalini Jindal, Grant Buchanan, Karen Chiam, and Tina Bianco-Miotto
- Abstract
Supplementary Table 1 from Global Levels of Specific Histone Modifications and an Epigenetic Gene Signature Predict Prostate Cancer Progression and Development
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- 2023
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16. Data from Comparative Biomarker Expression and RNA Integrity in Biospecimens Derived from Radical Retropubic and Robot-Assisted Laparoscopic Prostatectomies
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David J. Horsfall, Wayne D. Tilley, Robert L. Sutherland, Gail P. Risbridger, Judith A. Clements, Hong Wang, Ying Dong, James G. Kench, Hemamali Samaratunga, Peter D. Sutherland, Villis R. Marshall, Penelope A. Cohen, Thomas J. Dodd, Shalini Jindal, Tina Bianco-Miotto, and Carmela Ricciardelli
- Abstract
Background: Knowledge of preanalytic conditions that biospecimens are subjected to is critically important because novel surgical procedures, tissue sampling, handling, and storage might affect biomarker expression or invalidate tissue samples as analytes for some technologies.Methods: We investigated differences in RNA quality, gene expression by quantitative real-time PCR, and immunoreactive protein expression of selected prostate cancer biomarkers between tissues from retropubic radical prostatectomy (RRP) and robot-assisted laparoscopic prostatectomy (RALP). Sections of tissue microarray of 23 RALP and 22 RRP samples were stained with antibodies to androgen receptor (AR) and prostate-specific antigen (PSA) as intersite controls, and 14 other candidate biomarkers of research interest to three laboratories within the Australian Prostate Cancer BioResource tissue banking network. Quantitative real-time PCR was done for AR, PSA (KLK3), KLK2, KLK4, and HIF1A on RNA extracted from five RALP and five RRP frozen tissue cores.Results: No histologic differences were observed between RALP and RRP tissue. Biomarker staining grouped these samples into those with increased (PSA, CK8/18, CKHMW, KLK4), decreased (KLK2, KLK14), or no change in expression (AR, ghrelin, Ki67, PCNA, VEGF-C, PAR2, YB1, p63, versican, and chondroitin 0-sulfate) in RALP compared with RRP tissue. No difference in RNA quality or gene expression was detected between RALP and RRP tissue.Conclusions: Changes in biomarker expression between RALP and RRP tissue exist at the immunoreactive protein level, but the etiology is unclear.Impact: Future studies should account for changes in biomarker expression when using RALP tissues, and mixed cohorts of RALP and RRP tissue should be avoided. Cancer Epidemiol Biomarkers Prev; 19(7); 1755–65. ©2010 AACR.
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- 2023
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17. Supplementary Figure 5 from Global Levels of Specific Histone Modifications and an Epigenetic Gene Signature Predict Prostate Cancer Progression and Development
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Carmela Ricciardelli, David J. Horsfall, Wayne D. Tilley, Lisa M. Butler, Judith A. Clements, Gail P. Risbridger, Howard I. Scher, William L. Gerald, Susan M. Henshall, Robert L. Sutherland, Villis R. Marshall, Phillip D. Stricker, James G. Kench, Lisa G. Horvath, Wendy A. Raymond, Natalie K. Ryan, Melissa A. O'Loughlin, Marie A. Pickering, Mervyn Thomas, Tanya K. Day, Shalini Jindal, Grant Buchanan, Karen Chiam, and Tina Bianco-Miotto
- Abstract
Supplementary Figure 5 from Global Levels of Specific Histone Modifications and an Epigenetic Gene Signature Predict Prostate Cancer Progression and Development
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- 2023
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18. Supplementary Tables S2-S6 from Lipidomic Profiling of Clinical Prostate Cancer Reveals Targetable Alterations in Membrane Lipid Composition
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Johannes V. Swinnen, Margaret M. Centenera, Lisa G. Horvath, Wayne D. Tilley, David J. Lynn, Marten F. Snel, Paul J. Trim, Luke A. Selth, Zeyad D. Nassar, Etienne Waelkens, Rita Derua, Thomas Gevaert, James G. Kench, Jurgen Stahl, Rajdeep Das, Katarzyna Bloch, Frank Vanderhoydonc, Jonas Dehairs, Max Moldovan, David Waltregny, Muralidhararao Bagadi, Xander Spotbeen, Shadrack M. Mutuku, Swati Irani, Andrew D. Vincent, Jelle Machiels, Chui Yan Mah, and Lisa M. Butler
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Results of lipid association analyses
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- 2023
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19. Supplementary Figures S1-S6 from Lipidomic Profiling of Clinical Prostate Cancer Reveals Targetable Alterations in Membrane Lipid Composition
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Johannes V. Swinnen, Margaret M. Centenera, Lisa G. Horvath, Wayne D. Tilley, David J. Lynn, Marten F. Snel, Paul J. Trim, Luke A. Selth, Zeyad D. Nassar, Etienne Waelkens, Rita Derua, Thomas Gevaert, James G. Kench, Jurgen Stahl, Rajdeep Das, Katarzyna Bloch, Frank Vanderhoydonc, Jonas Dehairs, Max Moldovan, David Waltregny, Muralidhararao Bagadi, Xander Spotbeen, Shadrack M. Mutuku, Swati Irani, Andrew D. Vincent, Jelle Machiels, Chui Yan Mah, and Lisa M. Butler
- Abstract
Supplementary Figures S1-S6
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- 2023
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20. Supplementary Figure 3 from Epigenetic Deregulation Across Chromosome 2q14.2 Differentiates Normal from Prostate Cancer and Provides a Regional Panel of Novel DNA Methylation Cancer Biomarkers
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Susan J. Clark, Robert L. Sutherland, Miguel A. Peinado, Regina Mayor, Anne-Maree Haynes, Ruth Pe Benito, Susan M. Henshall, James G. Kench, Toby Hulf, Marcel W. Coolen, Bruce Tabor, Lisa G. Horvath, Kate I. Patterson, Aaron L. Statham, Jenny Z. Song, Wenjia Qu, Clare Stirzaker, and James Devaney
- Abstract
Supplementary Figure 3 from Epigenetic Deregulation Across Chromosome 2q14.2 Differentiates Normal from Prostate Cancer and Provides a Regional Panel of Novel DNA Methylation Cancer Biomarkers
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- 2023
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21. Supplementary Table S1 from Lipidomic Profiling of Clinical Prostate Cancer Reveals Targetable Alterations in Membrane Lipid Composition
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Johannes V. Swinnen, Margaret M. Centenera, Lisa G. Horvath, Wayne D. Tilley, David J. Lynn, Marten F. Snel, Paul J. Trim, Luke A. Selth, Zeyad D. Nassar, Etienne Waelkens, Rita Derua, Thomas Gevaert, James G. Kench, Jurgen Stahl, Rajdeep Das, Katarzyna Bloch, Frank Vanderhoydonc, Jonas Dehairs, Max Moldovan, David Waltregny, Muralidhararao Bagadi, Xander Spotbeen, Shadrack M. Mutuku, Swati Irani, Andrew D. Vincent, Jelle Machiels, Chui Yan Mah, and Lisa M. Butler
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Patient and sample clinical characteristics
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- 2023
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22. Supplementary Table and Figure Legends from Epigenetic Deregulation Across Chromosome 2q14.2 Differentiates Normal from Prostate Cancer and Provides a Regional Panel of Novel DNA Methylation Cancer Biomarkers
- Author
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Susan J. Clark, Robert L. Sutherland, Miguel A. Peinado, Regina Mayor, Anne-Maree Haynes, Ruth Pe Benito, Susan M. Henshall, James G. Kench, Toby Hulf, Marcel W. Coolen, Bruce Tabor, Lisa G. Horvath, Kate I. Patterson, Aaron L. Statham, Jenny Z. Song, Wenjia Qu, Clare Stirzaker, and James Devaney
- Abstract
Supplementary Table and Figure Legends from Epigenetic Deregulation Across Chromosome 2q14.2 Differentiates Normal from Prostate Cancer and Provides a Regional Panel of Novel DNA Methylation Cancer Biomarkers
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- 2023
- Full Text
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23. Supplementary Figure 4 from Epigenetic Deregulation Across Chromosome 2q14.2 Differentiates Normal from Prostate Cancer and Provides a Regional Panel of Novel DNA Methylation Cancer Biomarkers
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Susan J. Clark, Robert L. Sutherland, Miguel A. Peinado, Regina Mayor, Anne-Maree Haynes, Ruth Pe Benito, Susan M. Henshall, James G. Kench, Toby Hulf, Marcel W. Coolen, Bruce Tabor, Lisa G. Horvath, Kate I. Patterson, Aaron L. Statham, Jenny Z. Song, Wenjia Qu, Clare Stirzaker, and James Devaney
- Abstract
Supplementary Figure 4 from Epigenetic Deregulation Across Chromosome 2q14.2 Differentiates Normal from Prostate Cancer and Provides a Regional Panel of Novel DNA Methylation Cancer Biomarkers
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- 2023
- Full Text
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24. Supplementary Figure 1 from Global Levels of Specific Histone Modifications and an Epigenetic Gene Signature Predict Prostate Cancer Progression and Development
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Carmela Ricciardelli, David J. Horsfall, Wayne D. Tilley, Lisa M. Butler, Judith A. Clements, Gail P. Risbridger, Howard I. Scher, William L. Gerald, Susan M. Henshall, Robert L. Sutherland, Villis R. Marshall, Phillip D. Stricker, James G. Kench, Lisa G. Horvath, Wendy A. Raymond, Natalie K. Ryan, Melissa A. O'Loughlin, Marie A. Pickering, Mervyn Thomas, Tanya K. Day, Shalini Jindal, Grant Buchanan, Karen Chiam, and Tina Bianco-Miotto
- Abstract
Supplementary Figure 1 from Global Levels of Specific Histone Modifications and an Epigenetic Gene Signature Predict Prostate Cancer Progression and Development
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- 2023
- Full Text
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25. Supplementary Figure 1 from Epigenetic Deregulation Across Chromosome 2q14.2 Differentiates Normal from Prostate Cancer and Provides a Regional Panel of Novel DNA Methylation Cancer Biomarkers
- Author
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Susan J. Clark, Robert L. Sutherland, Miguel A. Peinado, Regina Mayor, Anne-Maree Haynes, Ruth Pe Benito, Susan M. Henshall, James G. Kench, Toby Hulf, Marcel W. Coolen, Bruce Tabor, Lisa G. Horvath, Kate I. Patterson, Aaron L. Statham, Jenny Z. Song, Wenjia Qu, Clare Stirzaker, and James Devaney
- Abstract
Supplementary Figure 1 from Epigenetic Deregulation Across Chromosome 2q14.2 Differentiates Normal from Prostate Cancer and Provides a Regional Panel of Novel DNA Methylation Cancer Biomarkers
- Published
- 2023
- Full Text
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26. Supplementary Table 2 from Global Levels of Specific Histone Modifications and an Epigenetic Gene Signature Predict Prostate Cancer Progression and Development
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Carmela Ricciardelli, David J. Horsfall, Wayne D. Tilley, Lisa M. Butler, Judith A. Clements, Gail P. Risbridger, Howard I. Scher, William L. Gerald, Susan M. Henshall, Robert L. Sutherland, Villis R. Marshall, Phillip D. Stricker, James G. Kench, Lisa G. Horvath, Wendy A. Raymond, Natalie K. Ryan, Melissa A. O'Loughlin, Marie A. Pickering, Mervyn Thomas, Tanya K. Day, Shalini Jindal, Grant Buchanan, Karen Chiam, and Tina Bianco-Miotto
- Abstract
Supplementary Table 2 from Global Levels of Specific Histone Modifications and an Epigenetic Gene Signature Predict Prostate Cancer Progression and Development
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- 2023
- Full Text
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27. Supplementary Figure 3 from Global Levels of Specific Histone Modifications and an Epigenetic Gene Signature Predict Prostate Cancer Progression and Development
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Carmela Ricciardelli, David J. Horsfall, Wayne D. Tilley, Lisa M. Butler, Judith A. Clements, Gail P. Risbridger, Howard I. Scher, William L. Gerald, Susan M. Henshall, Robert L. Sutherland, Villis R. Marshall, Phillip D. Stricker, James G. Kench, Lisa G. Horvath, Wendy A. Raymond, Natalie K. Ryan, Melissa A. O'Loughlin, Marie A. Pickering, Mervyn Thomas, Tanya K. Day, Shalini Jindal, Grant Buchanan, Karen Chiam, and Tina Bianco-Miotto
- Abstract
Supplementary Figure 3 from Global Levels of Specific Histone Modifications and an Epigenetic Gene Signature Predict Prostate Cancer Progression and Development
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- 2023
- Full Text
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28. Supplementary Table 1 from Comparative Biomarker Expression and RNA Integrity in Biospecimens Derived from Radical Retropubic and Robot-Assisted Laparoscopic Prostatectomies
- Author
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David J. Horsfall, Wayne D. Tilley, Robert L. Sutherland, Gail P. Risbridger, Judith A. Clements, Hong Wang, Ying Dong, James G. Kench, Hemamali Samaratunga, Peter D. Sutherland, Villis R. Marshall, Penelope A. Cohen, Thomas J. Dodd, Shalini Jindal, Tina Bianco-Miotto, and Carmela Ricciardelli
- Abstract
Supplementary Table 1 from Comparative Biomarker Expression and RNA Integrity in Biospecimens Derived from Radical Retropubic and Robot-Assisted Laparoscopic Prostatectomies
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- 2023
- Full Text
- View/download PDF
29. Data from Epigenetic Deregulation Across Chromosome 2q14.2 Differentiates Normal from Prostate Cancer and Provides a Regional Panel of Novel DNA Methylation Cancer Biomarkers
- Author
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Susan J. Clark, Robert L. Sutherland, Miguel A. Peinado, Regina Mayor, Anne-Maree Haynes, Ruth Pe Benito, Susan M. Henshall, James G. Kench, Toby Hulf, Marcel W. Coolen, Bruce Tabor, Lisa G. Horvath, Kate I. Patterson, Aaron L. Statham, Jenny Z. Song, Wenjia Qu, Clare Stirzaker, and James Devaney
- Abstract
Background: Previously, we showed that gene suppression commonly occurs across chromosome 2q14.2 in colorectal cancer, through a process of long-range epigenetic silencing (LRES), involving a combination of DNA methylation and repressive histone modifications. We now investigate whether LRES also occurs in prostate cancer across this 4-Mb region and whether differential DNA methylation of 2q14.2 genes could provide a regional panel of prostate cancer biomarkers.Methods: We used highly sensitive DNA methylation headloop PCR assays that can detect 10 to 25 pg of methylated DNA with a specificity of at least 1:1,000, and chromatin immunoprecipitation assays to investigate regional epigenetic remodeling across 2q14.2 in prostate cancer, in a cohort of 195 primary prostate tumors and 90 matched normal controls.Results: Prostate cancer cells exhibit concordant deacetylation and methylation of histone H3 Lysine 9 (H3K9Ac and H3K9me2, respectively), and localized DNA hypermethylation of EN1, SCTR, and INHBB and corresponding loss of H3K27me3. EN1 and SCTR were frequently methylated (65% and 53%, respectively), whereas INHBB was less frequently methylated.Conclusions: Consistent with LRES in colorectal cancer, we found regional epigenetic remodeling across 2q14.2 in prostate cancer. Concordant methylation of EN1 and SCTR was able to differentiate cancer from normal (P < 0.0001) and improved the diagnostic specificity of GSTP1 methylation for prostate cancer detection by 26%.Impact: For the first time we show that DNA methylation of EN1 and SCTR promoters provide potential novel biomarkers for prostate cancer detection and in combination with GSTP1 methylation can add increased specificity and sensitivity to improve diagnostic potential. Cancer Epidemiol Biomarkers Prev; 20(1); 148–59. ©2011 AACR.
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- 2023
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30. Data from Global Levels of Specific Histone Modifications and an Epigenetic Gene Signature Predict Prostate Cancer Progression and Development
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Carmela Ricciardelli, David J. Horsfall, Wayne D. Tilley, Lisa M. Butler, Judith A. Clements, Gail P. Risbridger, Howard I. Scher, William L. Gerald, Susan M. Henshall, Robert L. Sutherland, Villis R. Marshall, Phillip D. Stricker, James G. Kench, Lisa G. Horvath, Wendy A. Raymond, Natalie K. Ryan, Melissa A. O'Loughlin, Marie A. Pickering, Mervyn Thomas, Tanya K. Day, Shalini Jindal, Grant Buchanan, Karen Chiam, and Tina Bianco-Miotto
- Abstract
Background: Epigenetic alterations are common in prostate cancer, yet how these modifications contribute to carcinogenesis is poorly understood. We investigated whether specific histone modifications are prognostic for prostate cancer relapse, and whether the expression of epigenetic genes is altered in prostate tumorigenesis.Methods: Global levels of histone H3 lysine-18 acetylation (H3K18Ac) and histone H3 lysine-4 dimethylation (H3K4diMe) were assessed immunohistochemically in a prostate cancer cohort of 279 cases. Epigenetic gene expression was investigated in silico by analysis of microarray data from 23 primary prostate cancers (8 with biochemical recurrence and 15 without) and 7 metastatic lesions.Results: H3K18Ac and H3K4diMe are independent predictors of relapse-free survival, with high global levels associated with a 1.71-fold (P < 0.0001) and 1.80-fold (P = 0.006) increased risk of tumor recurrence, respectively. High levels of both histone modifications were associated with a 3-fold increased risk of relapse (P < 0.0001). Epigenetic gene expression profiling identified a candidate gene signature (DNMT3A, MBD4, MLL2, MLL3, NSD1, and SRCAP), which significantly discriminated nonmalignant from prostate tumor tissue (P = 0.0063) in an independent cohort.Conclusions: This study has established the importance of histone modifications in predicting prostate cancer relapse and has identified an epigenetic gene signature associated with prostate tumorigenesis.Impact: Our findings suggest that targeting the epigenetic enzymes specifically involved in a particular solid tumor may be a more effective approach. Moreover, testing for aberrant expression of epigenetic genes such as those identified in this study may be beneficial in predicting individual patient response to epigenetic therapies. Cancer Epidemiol Biomarkers Prev; 19(10); 2611–22. ©2010 AACR.
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- 2023
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31. Supplementary Figure 4 from Global Levels of Specific Histone Modifications and an Epigenetic Gene Signature Predict Prostate Cancer Progression and Development
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Carmela Ricciardelli, David J. Horsfall, Wayne D. Tilley, Lisa M. Butler, Judith A. Clements, Gail P. Risbridger, Howard I. Scher, William L. Gerald, Susan M. Henshall, Robert L. Sutherland, Villis R. Marshall, Phillip D. Stricker, James G. Kench, Lisa G. Horvath, Wendy A. Raymond, Natalie K. Ryan, Melissa A. O'Loughlin, Marie A. Pickering, Mervyn Thomas, Tanya K. Day, Shalini Jindal, Grant Buchanan, Karen Chiam, and Tina Bianco-Miotto
- Abstract
Supplementary Figure 4 from Global Levels of Specific Histone Modifications and an Epigenetic Gene Signature Predict Prostate Cancer Progression and Development
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- 2023
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32. Data from Lipidomic Profiling of Clinical Prostate Cancer Reveals Targetable Alterations in Membrane Lipid Composition
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Johannes V. Swinnen, Margaret M. Centenera, Lisa G. Horvath, Wayne D. Tilley, David J. Lynn, Marten F. Snel, Paul J. Trim, Luke A. Selth, Zeyad D. Nassar, Etienne Waelkens, Rita Derua, Thomas Gevaert, James G. Kench, Jurgen Stahl, Rajdeep Das, Katarzyna Bloch, Frank Vanderhoydonc, Jonas Dehairs, Max Moldovan, David Waltregny, Muralidhararao Bagadi, Xander Spotbeen, Shadrack M. Mutuku, Swati Irani, Andrew D. Vincent, Jelle Machiels, Chui Yan Mah, and Lisa M. Butler
- Abstract
Dysregulated lipid metabolism is a prominent feature of prostate cancer that is driven by androgen receptor (AR) signaling. Here we used quantitative mass spectrometry to define the “lipidome” in prostate tumors with matched benign tissues (n = 21), independent unmatched tissues (n = 47), and primary prostate explants cultured with the clinical AR antagonist enzalutamide (n = 43). Significant differences in lipid composition were detected and spatially visualized in tumors compared with matched benign samples. Notably, tumors featured higher proportions of monounsaturated lipids overall and elongated fatty acid chains in phosphatidylinositol and phosphatidylserine lipids. Significant associations between lipid profile and malignancy were validated in unmatched samples, and phospholipid composition was characteristically altered in patient tissues that responded to AR inhibition. Importantly, targeting tumor-related lipid features via inhibition of acetyl-CoA carboxylase 1 significantly reduced cellular proliferation and induced apoptosis in tissue explants. This characterization of the prostate cancer lipidome in clinical tissues reveals enhanced fatty acid synthesis, elongation, and desaturation as tumor-defining features, with potential for therapeutic targeting.Significance:This study identifies malignancy and treatment-associated changes in lipid composition of clinical prostate cancer tissues, suggesting that mediators of these lipidomic changes could be targeted using existing metabolic agents.
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- 2023
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33. Modelling economic risk to sea‐level rise and storms at the coastal margin
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Ashton Eaves, Paul Kench, Garry McDonald, Mark Dickson, and Belinda Storey
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Environmental Engineering ,Geography, Planning and Development ,Safety, Risk, Reliability and Quality ,Water Science and Technology - Published
- 2023
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34. Long-term ex-vivo normothermic perfusion of human split livers: a unique model to study new therapeutics and increase the number of available organs
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Ngee-Soon Lau, Mark Ly, Claude Dennis, Andrew Jacques, Marti Cabanes-Creus, Shamus Toomath, Joanna Huang, Nicole Mestrovic, Paul Yousif, Sumon Chanda, Chuanmin Wang, Leszek Lisowski, Ken Liu, James Kench, Geoffrey McCaughan, Michael Crawford, and Carlo Pulitano
- Abstract
Current perfusion technology only allows livers to be preserved ex-vivo for short periods. Long-term normothermic perfusion of livers is an emerging field with tremendous potential for the assessment, recovery, and modification of organs. In this study, we aimed develop a long-term model of ex-vivo perfusion including a surgical split and simultaneous perfusion of both partial grafts. Our long-term perfusion system included long-term oxygenators, a gas-mixer and a dialysis filter. Human livers declined for transplantation were perfused using a red-cell based perfusate under normothermic conditions (36°C) and then split and simultaneously perfused on separate machines. Ten human livers were split resulting in 20 partial grafts. The median ex-vivo survival was 165 hours (7 days). Long-term graft survival was demonstrated by lactate clearance, bile production, Factor-V production, and storage of adenosine triphosphate. The grafts that survived > 7 days demonstrated significantly higher bile production, Factor-V production, and hepatic arterial flow and significantly lower microvesicular steatosis. We report reliable long-term ex-vivo perfusion of human livers and demonstrate the ability to split and perfuse these organs using a reproducible protocol. This provides the opportunity for improved assessment of organs and could act as a model for the testing of therapeutics with a matched control.
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- 2023
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35. Sustained coral reef growth in the critical wave dissipation zone of a Maldivian atoll
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Paul S. Kench, Edward P. Beetham, Tracey Turner, Kyle M. Morgan, Susan D. Owen, Roger. F. McLean, Asian School of the Environment, and Earth Observatory of Singapore
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Environmental sciences ,QE1-996.5 ,Maldives ,General Earth and Planetary Sciences ,Geology ,GE1-350 ,Coral Reef ,Environmental engineering [Engineering] ,General Environmental Science - Abstract
Sea-level rise is expected to outpace the capacity of coral reefs to grow and maintain their wave protection function, exacerbating coastal flooding and erosion of adjacent shorelines and threatening coastal communities. Here we present a new method that yields highly-resolved direct measurements of contemporary reef accretion on a Maldivian atoll reef rim, the critical zone that induces wave breaking. Results incorporate the suite of physical and ecological processes that contribute to reef accumulation and show growth rates vary from 6.6 ± 12.5 mm.y−1 on the reef crest, and up to 3.1 ± 10.2 mm.y−1, and −0.5 ± 1.8 mm.yr−1 on the outer and central reef flat respectively. If these short-term results are maintained over decades, the reef crest could keep pace with current sea-level rise. Findings highlight the need to resolve contemporary reef accretion at the critical wave dissipation zone to improve predictions of future reef growth, and re-evaluate exposure of adjacent shorelines to coastal hazards.
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- 2022
36. Post-operative outcomes of inflammatory thoracic aortitis: a study of 41 patients from a cohort of 1119 surgical cases
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Trent Davidson, James G. Kench, Anthony M. Sammel, David Marshman, Ang Li, Lyn March, Hugh C. Caterson, Hugh Wolfenden, Hwei-Choo Soh, and Paul G. Bannon
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medicine.medical_specialty ,business.industry ,General Medicine ,medicine.disease ,Aortic repair ,Thoracic aortic aneurysm ,Surgery ,Giant cell arteritis ,Rheumatology ,Cohort ,Medicine ,Histopathology ,Median regression ,Post operative ,business ,Aortitis - Abstract
Aortitis is found in 2-12% of thoracic aortic aneurysm repair/replacement surgeries. Yet little is known about such patients' post-operative outcomes or the role of post-operative corticosteroids. The study was undertaken across three tertiary referral hospitals in Sydney, Australia. Prospectively collected data for all thoracic aortic repair/replacement patients between 2004 and 2018 was accessed from a national surgical registry and analysed. Histopathology records identified cases of inflammatory aortitis which were subclassified as clinically isolated aortitis (CIA), giant cell arteritis (GCA), Takayasu (TAK) or other aortitis. Between-group outcomes were compared utilising logistic and median regression analyses. Between 2004 and 2018, a total of 1119 thoracic aortic surgeries were performed of which 41 (3.7%) were inflammatory aortitis cases (66% CIA, 27% GCA, 5% TAK, 2% other). Eight out of 41 (20%) aortitis patients received post-operative corticosteroids. Compared to non-aortitis patients, the aortitis group was predominantly female (53.7% vs. 28.1%, p 0.05) between aortitis and non-aortitis groups for 30-day mortality (7.3% vs 6.5%), significant morbidity (14.6% vs. 22.4%), or infection (9.8% vs. 6.4%). Outcomes were similar for the non-corticosteroid-treated aortitis subgroup. Histologic evidence of inflammatory thoracic aortitis following surgery did not affect post-operative mortality or morbidity. Withholding corticosteroids did not adversely affect patient outcomes. These findings will assist rheumatologists and surgeons in the post-operative management of aortitis.
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- 2021
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37. Reef islands have continually adjusted to environmental change over the past two millennia
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P. S. Kench, C. Liang, M. R. Ford, S. D. Owen, M. Aslam, E. J. Ryan, T. Turner, E. Beetham, M. E. Dickson, W. Stephenson, A. Vila-Concejo, and R. F. McLean
- Subjects
Multidisciplinary ,General Physics and Astronomy ,General Chemistry ,General Biochemistry, Genetics and Molecular Biology - Abstract
Global environmental change is identified as a driver of physical transformation of coral reef islands over the past half-century, and next 100 years, posing major adaptation challenges to island nations. Here we resolve whether these recent documented changes in islands are unprecedented compared with the pre-industrial era. We utilise radiometric dating, geological, and remote sensing techniques to document the dynamics of a Maldivian reef island at millennial to decadal timescales. Results show the magnitude of island change over the past half-century (±40 m movement) is not unprecedented compared with paleo-dynamic evidence that reveals large-scale changes in island dimension, shape, beach levels, as well as positional changes of ±200 m since island formation ~1,500 years ago. Results highlight the value of a multi-temporal methodological approach to gain a deeper understanding of the dynamic trajectories of reef islands, to support development of adaptation strategies at timeframes relevant to human security.
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- 2023
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38. A deep learning system accurately classifies primary and metastatic cancers using passenger mutation patterns
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Jiao, Wei, Atwal, Gurnit, Polak, Paz, Karlic, Rosa, Cuppen, Edwin, Al-Shahrour, Fatima, Bailey, Peter J, Biankin, Andrew V, Boutros, Paul C, Campbell, Peter J, Chang, David K, Cooke, Susanna L, Deshpande, Vikram, Faltas, Bishoy M, Faquin, William C, Garraway, Levi, Getz, Gad, Grimmond, Sean M, Haider, Syed, Hoadley, Katherine A, Kaiser, Vera B, Kato, Mamoru, Kübler, Kirsten, Lazar, Alexander J, Li, Constance H, Louis, David N, Margolin, Adam, Martin, Sancha, Nahal-Bose, Hardeep K, Nielsen, G Petur, Nik-Zainal, Serena, Omberg, Larsson, P’ng, Christine, Perry, Marc D, Rheinbay, Esther, Rubin, Mark A, Semple, Colin A, Sgroi, Dennis C, Shibata, Tatsuhiro, Siebert, Reiner, Smith, Jaclyn, Stein, Lincoln D, Stobbe, Miranda D, Sun, Ren X, Thai, Kevin, Wright, Derek W, Wu, Chin-Lee, Yuan, Ke, Zhang, Junjun, Danyi, Alexandra, de Ridder, Jeroen, van Herpen, Carla, Lolkema, Martijn P, Steeghs, Neeltje, Morris, Quaid D, Aaltonen, Lauri A, Abascal, Federico, Abeshouse, Adam, Aburatani, Hiroyuki, Adams, David J, Agrawal, Nishant, Ahn, Keun Soo, Ahn, Sung-Min, Aikata, Hiroshi, Akbani, Rehan, Akdemir, Kadir C, Al-Ahmadie, Hikmat, Al-Sedairy, Sultan T, Alawi, Malik, Albert, Monique, Aldape, Kenneth, Alexandrov, Ludmil B, Ally, Adrian, Alsop, Kathryn, Alvarez, Eva G, Amary, Fernanda, Amin, Samirkumar B, Aminou, Brice, Ammerpohl, Ole, Anderson, Matthew J, Ang, Yeng, Antonello, Davide, Anur, Pavana, Aparicio, Samuel, Appelbaum, Elizabeth L, Arai, Yasuhito, Aretz, Axel, Arihiro, Koji, Ariizumi, Shun-ichi, Armenia, Joshua, Arnould, Laurent, Asa, Sylvia, Assenov, Yassen, Aukema, Sietse, Auman, J Todd, Aure, Miriam RR, Awadalla, Philip, Aymerich, Marta, Bader, Gary D, Baez-Ortega, Adrian, Bailey, Matthew H, Balasundaram, Miruna, Balu, Saianand, Bandopadhayay, Pratiti, Banks, Rosamonde E, Barbi, Stefano, Barbour, Andrew P, Barenboim, Jonathan, Barnholtz-Sloan, Jill, Barr, Hugh, Barrera, Elisabet, Bartlett, John, Bartolome, Javier, Bassi, Claudio, Bathe, Oliver F, Baumhoer, Daniel, Bavi, Prashant, Baylin, Stephen B, Bazant, Wojciech, Beardsmore, Duncan, Beck, Timothy A, Behjati, Sam, Behren, Andreas, Niu, Beifang, Bell, Cindy, Beltran, Sergi, Benz, Christopher, Berchuck, Andrew, Bergmann, Anke K, Bergstrom, Erik N, Berman, Benjamin P, Berney, Daniel M, Bernhart, Stephan H, Beroukhim, Rameen, Berrios, Mario, Bersani, Samantha, Bertl, Johanna, Betancourt, Miguel, Bhandari, Vinayak, Bhosle, Shriram G, Bieg, Matthias, Bigner, Darell, Binder, Hans, Birney, Ewan, Birrer, Michael, Biswas, Nidhan K, Bjerkehagen, Bodil, Bodenheimer, Tom, Boice, Lori, Bonizzato, Giada, De Bono, Johann S, Boot, Arnoud, Bootwalla, Moiz S, Borg, Ake, Borkhardt, Arndt, Boroevich, Keith A, Borozan, Ivan, Borst, Christoph, Bosenberg, Marcus, Bosio, Mattia, Boultwood, Jacqueline, Bourque, Guillaume, Bova, G Steven, Bowen, David T, Bowlby, Reanne, Bowtell, David DL, Boyault, Sandrine, Boyce, Rich, Boyd, Jeffrey, Brazma, Alvis, Brennan, Paul, Brewer, Daniel S, Brinkman, Arie B, Bristow, Robert G, Broaddus, Russell R, Brock, Jane E, Brock, Malcolm, Broeks, Annegien, Brooks, Angela N, Brooks, Denise, Brors, Benedikt, Brunak, Søren, Bruxner, Timothy JC, Bruzos, Alicia L, Buchanan, Alex, Buchhalter, Ivo, Buchholz, Christiane, Bullman, Susan, Burke, Hazel, Burkhardt, Birgit, Burns, Kathleen H, Busanovich, John, Bustamante, Carlos D, Butler, Adam P, Butte, Atul J, Byrne, Niall J, Børresen-Dale, Anne-Lise, Caesar-Johnson, Samantha J, Cafferkey, Andy, Cahill, Declan, Calabrese, Claudia, Caldas, Carlos, Calvo, Fabien, Camacho, Niedzica, Campo, Elias, Cantù, Cinzia, Cao, Shaolong, Carey, Thomas E, Carlevaro-Fita, Joana, Carlsen, Rebecca, Cataldo, Ivana, Cazzola, Mario, Cebon, Jonathan, Cerfolio, Robert, Chadwick, Dianne E, Chakravarty, Dimple, Chalmers, Don, Chan, Calvin Wing Yiu, Chan, Kin, Chan-Seng-Yue, Michelle, Chandan, Vishal S, Chanock, Stephen J, Chantrill, Lorraine A, Chateigner, Aurélien, Chatterjee, Nilanjan, Chayama, Kazuaki, Chen, Hsiao-Wei, Chen, Jieming, Chen, Ken, Chen, Yiwen, Chen, Zhaohong, Cherniack, Andrew D, Chien, Jeremy, Chiew, Yoke-Eng, Chin, Suet-Feung, Cho, Juok, Cho, Sunghoon, Choi, Jung Kyoon, Choi, Wan, Chomienne, Christine, Chong, Zechen, Choo, Su Pin, Chou, Angela, Christ, Angelika N, Christie, Elizabeth L, Chuah, Eric, Cibulskis, Carrie, Cibulskis, Kristian, Cingarlini, Sara, Clapham, Peter, Claviez, Alexander, Cleary, Sean, Cloonan, Nicole, Cmero, Marek, Collins, Colin C, Connor, Ashton A, Cooper, Colin S, Cope, Leslie, Corbo, Vincenzo, Cordes, Matthew G, Cordner, Stephen M, Cortés-Ciriano, Isidro, Covington, Kyle, Cowin, Prue A, Craft, Brian, Craft, David, Creighton, Chad J, Cun, Yupeng, Curley, Erin, Cutcutache, Ioana, Czajka, Karolina, Czerniak, Bogdan, Dagg, Rebecca A, Danilova, Ludmila, Davi, Maria Vittoria, Davidson, Natalie R, Davies, Helen, Davis, Ian J, Davis-Dusenbery, Brandi N, Dawson, Kevin J, De La Vega, Francisco M, De Paoli-Iseppi, Ricardo, Defreitas, Timothy, Dei Tos, Angelo P, Delaneau, Olivier, Demchok, John A, Demeulemeester, Jonas, Demidov, German M, Demircioğlu, Deniz, Dennis, Nening M, Denroche, Robert E, Dentro, Stefan C, Desai, Nikita, Deshwar, Amit G, Desmedt, Christine, Deu-Pons, Jordi, Dhalla, Noreen, Dhani, Neesha C, Dhingra, Priyanka, Dhir, Rajiv, DiBiase, Anthony, Diamanti, Klev, Ding, Li, Ding, Shuai, Dinh, Huy Q, Dirix, Luc, Doddapaneni, HarshaVardhan, Donmez, Nilgun, Dow, Michelle T, Drapkin, Ronny, Drechsel, Oliver, Drews, Ruben M, Serge, Serge, Dudderidge, Tim, Dueso-Barroso, Ana, Dunford, Andrew J, Dunn, Michael, Dursi, Lewis Jonathan, Duthie, Fraser R, Dutton-Regester, Ken, Eagles, Jenna, Easton, Douglas F, Edmonds, Stuart, Edwards, Paul A, Edwards, Sandra E, Eeles, Rosalind A, Ehinger, Anna, Eils, Juergen, Eils, Roland, El-Naggar, Adel, Eldridge, Matthew, Ellrott, Kyle, Erkek, Serap, Escaramis, Georgia, Espiritu, Shadrielle MG, Estivill, Xavier, Etemadmoghadam, Dariush, Eyfjord, Jorunn E, Fan, Daiming, Fan, Yu, Farcas, Claudiu, Fassan, Matteo, Fatima, Aquila, Favero, Francesco, Fayzullaev, Nodirjon, Felau, Ina, Fereday, Sian, Ferguson, Martin L, Ferretti, Vincent, Feuerbach, Lars, Field, Matthew A, Fink, J Lynn, Finocchiaro, Gaetano, Fisher, Cyril, Fittall, Matthew W, Fitzgerald, Anna, Fitzgerald, Rebecca C, Flanagan, Adrienne M, Fleshner, Neil E, Flicek, Paul, Foekens, John A, Fong, Kwun M, Fonseca, Nuno A, Foster, Christopher S, Fox, Natalie S, Fraser, Michael, Frazer, Scott, Frenkel-Morgenstern, Milana, Friedman, William, Frigola, Joan, Fronick, Catrina C, Fujimoto, Akihiro, Fujita, Masashi, Fukayama, Masashi, Fulton, Lucinda A, Fulton, Robert S, Furuta, Mayuko, Futreal, P Andrew, Füllgrabe, Anja, Gabriel, Stacey B, Gallinger, Steven, Gambacorti-Passerini, Carlo, Gao, Jianjiong, Gao, Shengjie, Garred, Øystein, Garrison, Erik, Garsed, Dale W, Gehlenborg, Nils, Gelpi, Josep LL, George, Joshy, Gerhard, Daniela S, Gerhauser, Clarissa, Gershenwald, Jeffrey E, Gerstein, Mark, Gerstung, Moritz, Ghori, Mohammed, Ghossein, Ronald, Giama, Nasra H, Gibbs, Richard A, Gibson, Bob, Gill, Anthony J, Gill, Pelvender, Giri, Dilip D, Glodzik, Dominik, Gnanapragasam, Vincent J, Goebler, Maria Elisabeth, Goldman, Mary J, Gomez, Carmen, Gonzalez, Santiago, Gonzalez-Perez, Abel, Gordenin, Dmitry A, Gossage, James, Gotoh, Kunihito, Govindan, Ramaswamy, Grabau, Dorthe, Graham, Janet S, Grant, Robert C, Green, Anthony R, Green, Eric, Greger, Liliana, Grehan, Nicola, Grimaldi, Sonia, Grossman, Robert L, Grundhoff, Adam, Gundem, Gunes, Guo, Qianyun, Gupta, Manaswi, Gupta, Shailja, Gut, Ivo G, Gut, Marta, Göke, Jonathan, Ha, Gavin, Haake, Andrea, Haan, David, Haas, Siegfried, Haase, Kerstin, Haber, James E, Habermann, Nina, Hach, Faraz, Hama, Natsuko, Hamdy, Freddie C, Hamilton, Anne, Hamilton, Mark P, Han, Leng, Hanna, George B, Hansmann, Martin, Haradhvala, Nicholas J, Harismendy, Olivier, Harliwong, Ivon, Harmanci, Arif O, Harrington, Eoghan, Hasegawa, Takanori, Haussler, David, Hawkins, Steve, Hayami, Shinya, Hayashi, Shuto, Hayes, D Neil, Hayes, Stephen J, Hayward, Nicholas K, Hazell, Steven, He, Yao, Heath, Allison P, Heath, Simon C, Hedley, David, Hegde, Apurva M, Heiman, David I, Heinold, Michael C, Heins, Zachary, Heisler, Lawrence E, Hellstrom-Lindberg, Eva, Helmy, Mohamed, Heo, Seong Gu, Hepperla, Austin J, Heredia-Genestar, José María, Herrmann, Carl, Hersey, Peter, Hess, Julian M, Hilmarsdottir, Holmfridur, Hinton, Jonathan, Hirano, Satoshi, Hiraoka, Nobuyoshi, Hobolth, Asger, Hodzic, Ermin, Hoell, Jessica I, Hoffmann, Steve, Hofmann, Oliver, Holbrook, Andrea, Holik, Aliaksei Z, Hollingsworth, Michael A, Holmes, Oliver, Holt, Robert A, Hong, Chen, Hong, Eun Pyo, Hong, Jongwhi H, Hooijer, Gerrit K, Hornshøj, Henrik, Hosoda, Fumie, Hou, Yong, Hovestadt, Volker, Howat, William, Hoyle, Alan P, Hruban, Ralph H, Hu, Jianhong, Hu, Taobo, Hua, Xing, Huang, Kuan-lin, Huang, Mei, Huang, Mi Ni, Huang, Vincent, Huang, Yi, Huber, Wolfgang, Hudson, Thomas J, Hummel, Michael, Hung, Jillian A, Huntsman, David, Hupp, Ted R, Huse, Jason, Huska, Matthew R, Hutter, Barbara, Hutter, Carolyn M, Hübschmann, Daniel, Iacobuzio-Donahue, Christine A, Imbusch, Charles David, Imielinski, Marcin, Imoto, Seiya, Isaacs, William B, Isaev, Keren, Ishikawa, Shumpei, Iskar, Murat, Islam, SM Ashiqul, Ittmann, Michael, Ivkovic, Sinisa, Izarzugaza, Jose MG, Jacquemier, Jocelyne, Jakrot, Valerie, Jamieson, Nigel B, Jang, Gun Ho, Jang, Se Jin, Jayaseelan, Joy C, Jayasinghe, Reyka, Jefferys, Stuart R, Jegalian, Karine, Jennings, Jennifer L, Jeon, Seung-Hyup, Jerman, Lara, Ji, Yuan, Johansson, Peter A, Johns, Amber L, Johns, Jeremy, Johnson, Rory, Johnson, Todd A, Jolly, Clemency, Joly, Yann, Jonasson, Jon G, Jones, Corbin D, Jones, David R, Jones, David TW, Jones, Nic, Jones, Steven JM, Jonkers, Jos, Ju, Young Seok, Juhl, Hartmut, Jung, Jongsun, Juul, Malene, Juul, Randi Istrup, Juul, Sissel, Jäger, Natalie, Kabbe, Rolf, Kahles, Andre, Kahraman, Abdullah, Kakavand, Hojabr, Kalimuthu, Sangeetha, von Kalle, Christof, Kang, Koo Jeong, Karaszi, Katalin, Karlan, Beth, Karlić, Rosa, Karsch, Dennis, Kasaian, Katayoon, Kassahn, Karin S, Katai, Hitoshi, Katoh, Hiroto, Kawakami, Yoshiiku, Kay, Jonathan D, Kazakoff, Stephen H, Kazanov, Marat D, Keays, Maria, Kebebew, Electron, Kefford, Richard F, Kellis, Manolis, Kench, James G, Kennedy, Catherine J, Kerssemakers, Jules NA, Khoo, David, Khoo, Vincent, Khuntikeo, Narong, Khurana, Ekta, Kilpinen, Helena, Kim, Hark Kyun, Kim, Hyung-Lae, Kim, Hyung-Yong, Kim, Hyunghwan, Kim, Jaegil, Kim, Jihoon, Kim, Jong K, Kim, Youngwook, King, Tari A, Klapper, Wolfram, Kleinheinz, Kortine, Klimczak, Leszek J, Knappskog, Stian, Kneba, Michael, Knoppers, Bartha M, Koh, Youngil, Komorowski, Jan, Komura, Daisuke, Komura, Mitsuhiro, Kong, Gu, Kool, Marcel, Korbel, Jan O, Korchina, Viktoriya, Korshunov, Andrey, Koscher, Michael, Koster, Roelof, Kote-Jarai, Zsofia, Koures, Antonios, Kovacevic, Milena, Kremeyer, Barbara, Kretzmer, Helene, Kreuz, Markus, Krishnamurthy, Savitri, Kube, Dieter, Kumar, Kiran, Kumar, Pardeep, Kumar, Sushant, Kumar, Yogesh, Kundra, Ritika, Küppers, Ralf, Lagergren, Jesper, Lai, Phillip H, Laird, Peter W, Lakhani, Sunil R, Lalansingh, Christopher M, Lalonde, Emilie, Lamaze, Fabien C, Lambert, Adam, Lander, Eric, Landgraf, Pablo, Landoni, Luca, Langerød, Anita, Lanzós, Andrés, Larsimont, Denis, Larsson, Erik, Lathrop, Mark, Lau, Loretta MS, Lawerenz, Chris, Lawlor, Rita T, Lawrence, Michael S, Lazic, Ana Mijalkovic, Le, Xuan, Lee, Darlene, Lee, Donghoon, Lee, Eunjung Alice, Lee, Hee Jin, Lee, Jake June-Koo, Lee, Jeong-Yeon, Lee, Juhee, Lee, Ming Ta Michael, Lee-Six, Henry, Lehmann, Kjong-Van, Lehrach, Hans, Lenze, Dido, Leonard, Conrad R, Leongamornlert, Daniel A, Leshchiner, Ignaty, Letourneau, Louis, Letunic, Ivica, Levine, Douglas A, Lewis, Lora, Ley, Tim, Li, Chang, Li, Haiyan Irene, Li, Jun, Li, Lin, Li, Shantao, Li, Siliang, Li, Xiaobo, Li, Xiaotong, Li, Xinyue, Li, Yilong, Liang, Han, Liang, Sheng-Ben, Lichter, Peter, Lin, Pei, Lin, Ziao, Linehan, WM, Lingjærde, Ole Christian, Liu, Dongbing, Liu, Eric Minwei, Liu, Fei-Fei Fei, Liu, Fenglin, Liu, Jia, Liu, Xingmin, Livingstone, Julie, Livitz, Dimitri, Livni, Naomi, Lochovsky, Lucas, Loeffler, Markus, Long, Georgina V, Lopez-Guillermo, Armando, Lou, Shaoke, Lovat, Laurence B, Lu, Yiling, Lu, Yong-Jie, Lu, Youyong, Luchini, Claudio, Lungu, Ilinca, Luo, Xuemei, Luxton, Hayley J, Lynch, Andy G, Lype, Lisa, López, Cristina, López-Otín, Carlos, Z, Eric, Ma, Yussanne, MacGrogan, Gaetan, MacRae, Shona, Macintyre, Geoff, Madsen, Tobias, Maejima, Kazuhiro, Mafficini, Andrea, Maglinte, Dennis T, Maitra, Arindam, Majumder, Partha P, Malcovati, Luca, Malikic, Salem, Malleo, Giuseppe, Mann, Graham J, Mantovani-Löffler, Luisa, Marchal, Kathleen, Marchegiani, Giovanni, Mardis, Elaine R, Margolin, Adam A, Marin, Maximillian G, Markowetz, Florian, Markowski, Julia, Marks, Jeffrey, Marques-Bonet, Tomas, Marra, Marco A, Marsden, Luke, Martens, John WM, Martin-Subero, Jose I, Martincorena, Iñigo, 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Deurzen, Carolien HM, van de Vijver, Marc J, Veer, L van’t, and von Mering, Christian
- Subjects
Human Biology & Physiology ,Ecology,Evolution & Ethology ,Tumour Biology ,Genetics & Genomics ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
In cancer, the primary tumour’s organ of origin and histopathology are the strongest determinants of its clinical behaviour, but in 3% of cases a patient presents with a metastatic tumour and no obvious primary. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we train a deep learning classifier to predict cancer type based on patterns of somatic passenger mutations detected in whole genome sequencing (WGS) of 2606 tumours representing 24 common cancer types produced by the PCAWG Consortium. Our classifier achieves an accuracy of 91% on held-out tumor samples and 88% and 83% respectively on independent primary and metastatic samples, roughly double the accuracy of trained pathologists when presented with a metastatic tumour without knowledge of the primary. Surprisingly, adding information on driver mutations reduced accuracy. Our results have clinical applicability, underscore how patterns of somatic passenger mutations encode the state of the cell of origin, and can inform future strategies to detect the source of circulating tumour DNA.
- Published
- 2023
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39. Combined burden and functional impact tests for cancer driver discovery using DriverPower
- Author
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Human Biology & Physiology ,Ecology,Evolution & Ethology ,Tumour Biology ,Genetics & Genomics ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
The discovery of driver mutations is one of the key motivations for cancer genome sequencing. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumour types, we describe DriverPower, a software package that uses mutational burden and functional impact evidence to identify driver mutations in coding and non-coding sites within cancer whole genomes. Using a total of 1373 genomic features derived from public sources, DriverPower’s background mutation model explains up to 93% of the regional variance in the mutation rate across multiple tumour types. By incorporating functional impact scores, we are able to further increase the accuracy of driver discovery. Testing across a collection of 2583 cancer genomes from the PCAWG project, DriverPower identifies 217 coding and 95 non-coding driver candidates. Comparing to six published methods used by the PCAWG Drivers and Functional Interpretation Working Group, DriverPower has the highest F1 score for both coding and non-coding driver discovery. This demonstrates that DriverPower is an effective framework for computational driver discovery.
- Published
- 2023
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40. Integrative pathway enrichment analysis of multivariate omics data
- Author
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Paczkowska, Marta, Barenboim, Jonathan, Sintupisut, Nardnisa, Fox, Natalie S, Zhu, Helen, Abd-Rabbo, Diala, Mee, Miles W, Boutros, Paul C, Abascal, Federico, Amin, Samirkumar B, Bader, Gary D, Beroukhim, Rameen, Bertl, Johanna, Boroevich, Keith A, Brunak, Søren, Campbell, Peter J, Carlevaro-Fita, Joana, Chakravarty, Dimple, Chan, Calvin Wing Yiu, Chen, Ken, Choi, Jung Kyoon, Deu-Pons, Jordi, Dhingra, Priyanka, Diamanti, Klev, Feuerbach, Lars, Fink, J Lynn, Fonseca, Nuno A, Frigola, Joan, Gambacorti-Passerini, Carlo, Garsed, Dale W, Gerstein, Mark, Getz, Gad, Gonzalez-Perez, Abel, Guo, Qianyun, Gut, Ivo G, Haan, David, Hamilton, Mark P, Haradhvala, Nicholas J, Harmanci, Arif O, Helmy, Mohamed, Herrmann, Carl, Hess, Julian M, Hobolth, Asger, Hodzic, Ermin, Hong, Chen, Hornshøj, Henrik, Isaev, Keren, Izarzugaza, Jose MG, Johnson, Rory, Johnson, Todd A, Juul, Malene, Juul, Randi Istrup, Kahles, Andre, Kahraman, Abdullah, Kellis, Manolis, Khurana, Ekta, Kim, Jaegil, Kim, Jong K, Kim, 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Vijver, Marc J, and Veer, L van’t
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Human Biology & Physiology ,Ecology,Evolution & Ethology ,Tumour Biology ,Genetics & Genomics ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
Multi-omics datasets represent distinct aspects of the central dogma of molecular biology. Such high-dimensional molecular profiles pose challenges to data interpretation and hypothesis generation. ActivePathways is an integrative method that discovers significantly enriched pathways across multiple datasets using statistical data fusion, rationalizes contributing evidence and highlights associated genes. As part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumor types, we integrated genes with coding and non-coding mutations and revealed frequently mutated pathways and additional cancer genes with infrequent mutations. We also analyzed prognostic molecular pathways by integrating genomic and transcriptomic features of 1780 breast cancers and highlighted associations with immune response and anti-apoptotic signaling. Integration of ChIP-seq and RNA-seq data for master regulators of the Hippo pathway across normal human tissues identified processes of tissue regeneration and stem cell regulation. ActivePathways is a versatile method that improves systems-level understanding of cellular organization in health and disease through integration of multiple molecular datasets and pathway annotations.
- Published
- 2023
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41. Pathway and network analysis of more than 2500 whole cancer genomes
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Human Biology & Physiology ,Ecology,Evolution & Ethology ,Tumour Biology ,Genetics & Genomics ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
The catalog of cancer driver mutations in protein-coding genes has greatly expanded in the past decade. However, non-coding cancer driver mutations are less well-characterized and only a handful of recurrent non-coding mutations, most notably TERT promoter mutations, have been reported. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancer across 38 tumor types, we perform multi-faceted pathway and network analyses of non-coding mutations across 2583 whole cancer genomes from 27 tumor types compiled by the ICGC/TCGA PCAWG project that was motivated by the success of pathway and network analyses in prioritizing rare mutations in protein-coding genes. While few non-coding genomic elements are recurrently mutated in this cohort, we identify 93 genes harboring non-coding mutations that cluster into several modules of interacting proteins. Among these are promoter mutations associated with reduced mRNA expression in TP53, TLE4, and TCF4. We find that biological processes had variable proportions of coding and non-coding mutations, with chromatin remodeling and proliferation pathways altered primarily by coding mutations, while developmental pathways, including Wnt and Notch, altered by both coding and non-coding mutations. RNA splicing is primarily altered by non-coding mutations in this cohort, and samples containing non-coding mutations in well-known RNA splicing factors exhibit similar gene expression signatures as samples with coding mutations in these genes. These analyses contribute a new repertoire of possible cancer genes and mechanisms that are altered by non-coding mutations and offer insights into additional cancer vulnerabilities that can be investigated for potential therapeutic treatments.
- Published
- 2023
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42. Divergent mutational processes distinguish hypoxic and normoxic tumours
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Human Biology & Physiology ,Ecology,Evolution & Ethology ,Tumour Biology ,Genetics & Genomics ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
Many primary tumours have low levels of molecular oxygen (hypoxia), and hypoxic tumours respond poorly to therapy. Pan-cancer molecular hallmarks of tumour hypoxia remain poorly understood, with limited comprehension of its associations with specific mutational processes, non-coding driver genes and evolutionary features. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumour types, we quantify hypoxia in 1188 tumours spanning 27 cancer types. Elevated hypoxia associates with increased mutational load across cancer types, irrespective of underlying mutational class. The proportion of mutations attributed to several mutational signatures of unknown aetiology directly associates with the level of hypoxia, suggesting underlying mutational processes for these signatures. At the gene level, driver mutations in TP53, MYC and PTEN are enriched in hypoxic tumours, and mutations in PTEN interact with hypoxia to direct tumour evolutionary trajectories. Overall, hypoxia plays a critical role in shaping the genomic and evolutionary landscapes of cancer.
- Published
- 2023
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43. Genomic footprints of activated telomere maintenance mechanisms in cancer
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Okusaka, Takuji, Omberg, Larsson, Ong, Choon Kiat, Ott, German, Ouellette, BF Francis, P’ng, Christine, Paczkowska, Marta, Paiella, Salvatore, Pairojkul, Chawalit, Pajic, Marina, Pan-Hammarström, Qiang, Papaemmanuil, Elli, Papatheodorou, Irene, Paramasivam, Nagarajan, Park, Ji Wan, Park, Joong-Won, Park, Keunchil, Park, Kiejung, Parker, Joel S, Parsons, Simon L, Pass, Harvey, Pasternack, Danielle, Pastore, Alessandro, Patch, Ann-Marie, Pauporté, Iris, Pea, Antonio, Pedamallu, Chandra Sekhar, Pedersen, Jakob Skou, Pederzoli, Paolo, Peifer, Martin, Pennell, Nathan A, Perou, Charles M, Perry, Marc D, Petersen, Gloria M, Peto, Myron, Petrelli, Nicholas, Petryszak, Robert, Pfister, Stefan M, Phillips, Mark, Pich, Oriol, Pickett, Hilda A, Pihl, Todd D, Pillay, Nischalan, Pinder, Sarah, Pinese, Mark, Pinho, Andreia V, Pitkänen, Esa, Pivot, Xavier, Piñeiro-Yáñez, Elena, Planko, Laura, Plass, Christoph, Polak, Paz, Pons, Tirso, Popescu, Irinel, Potapova, Olga, Prasad, Aparna, Preston, Shaun R, 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Elisabetta, Serra, Stefano, Sgroi, Dennis C, Shah, Nimish C, Shahabi, Sagedeh, Shang, Catherine A, Shang, Ping, Shapira, Ofer, Shelton, Troy, Shen, Ciyue, Shen, Hui, Shepherd, Rebecca, Shi, Ruian, Shi, Yan, Shiah, Yu-Jia, Shibata, Tatsuhiro, Shih, Juliann, Shimizu, Eigo, Shimizu, Kiyo, Shin, Seung Jun, Shiraishi, Yuichi, Shmaya, Tal, Shmulevich, Ilya, Shorser, Solomon I, Short, Charles, Shrestha, Raunak, Shringarpure, Suyash S, Shriver, Craig, Shuai, Shimin, Siebert, Reiner, Sieuwerts, Anieta M, Signoretti, Sabina, Sikora, Katarzyna O, Simbolo, Michele, Simon, Ronald, Simons, Janae V, Simpson, Jared T, Simpson, Peter T, Singer, Samuel, Sinnott-Armstrong, Nasa, Sipahimalani, Payal, Skelly, Tara J, Smid, Marcel, Smith, Jaclyn, Smith-McCune, Karen, Socci, Nicholas D, Sofia, Heidi J, Soloway, Matthew G, Song, Lei, Sood, Anil K, Sothi, Sharmila, Sotiriou, Christos, Soulette, Cameron M, Span, Paul N, Spellman, Paul T, Sperandio, Nicola, Spillane, Andrew J, Spiro, Oliver, Spring, Jonathan, 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Qinying, Xu, Yanxun, Xue, Hong, Yachida, Shinichi, Yakneen, Sergei, Yamaguchi, Rui, Yamaguchi, Takafumi N, Yamamoto, Masakazu, Yamamoto, Shogo, Yamaue, Hiroki, Yang, Fan, Yang, Huanming, Yang, Jean Y, Yang, Liming, Yang, Shanlin, Yang, Tsun-Po, Yang, Yang, Yaspo, Marie-Laure, Yates, Lucy, Yau, Christina, Ye, Chen, Ye, Kai, Yellapantula, Venkata D, Yoon, Christopher J, Yousif, Fouad, Yu, Jun, Yu, Kaixian, Yu, Willie, Yu, Yingyan, Yuan, Ke, Yuan, Yuan, Yuen, Denis, Yung, Christina K, Zaikova, Olga, Zapatka, Marc, Zenklusen, Jean C, Zenz, Thorsten, Zeps, Nikolajs, Zhang, Fan, Zhang, Hailei, Zhang, Hongwei, Zhang, Hongxin, Zhang, Jiashan, Zhang, Jing, Zhang, Junjun, Zhang, Xiuqing, Zhang, Xuanping, Zhang, Yan, Zhang, Zemin, Zhao, Zhongming, Zheng, Liangtao, Zheng, Xiuqing, Zhou, Wanding, Zhou, Yong, Zhu, Bin, Zhu, Hongtu, Zhu, Jingchun, Zhu, Shida, Zou, Lihua, Zou, Xueqing, deFazio, Anna, van As, Nicholas, van Deurzen, Carolien HM, van de Vijver, Marc J, Veer, L van’t, and von Mering, Christian
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Human Biology & Physiology ,Ecology,Evolution & Ethology ,Tumour Biology ,Genetics & Genomics ,Structural Biology & Biophysics ,Computational & Systems Biology - Abstract
Cancers require telomere maintenance mechanisms for unlimited replicative potential. They achieve this through TERT activation or alternative telomere lengthening associated with ATRX or DAXX loss. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we dissect whole-genome sequencing data of over 2500 matched tumor-control samples from 36 different tumor types aggregated within the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium to characterize the genomic footprints of these mechanisms. While the telomere content of tumors with ATRX or DAXX mutations (ATRX/DAXXtrunc) is increased, tumors with TERT modifications show a moderate decrease of telomere content. One quarter of all tumor samples contain somatic integrations of telomeric sequences into non-telomeric DNA. This fraction is increased to 80% prevalence in ATRX/DAXXtrunc tumors, which carry an aberrant telomere variant repeat (TVR) distribution as another genomic marker. The latter feature includes enrichment or depletion of the previously undescribed singleton TVRs TTCGGG and TTTGGG, respectively. Our systematic analysis provides new insight into the recurrent genomic alterations associated with telomere maintenance mechanisms in cancer.
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- 2023
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44. Banff 2016 Global Assessment and Quantitative Scoring for T Cell-Mediated Liver Transplant Rejection are Interchangeable
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Maryam Eghtedari, Catriona McKenzie, Lauren C. Y. Tang, Avik Majumdar, and James G. Kench
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Article Subject - Abstract
Introduction. Histopathological assessment of liver biopsies is the current “gold standard” for diagnosing graft dysfunction after liver transplantation (LT), as graft dysfunction can have nonspecific clinical presentations and inconsistent patterns of liver biochemical dysfunction. Most commonly, post-LT, graft dysfunction within the first year, is due to acute T-cell mediated rejection (TCMR) which is characterised histologically by the degree of portal inflammation (PI), bile duct damage (BDD), and venous endothelial inflammation (VEI). This study aimed to establish the relationship between global assessment, which is the global grading of rejection using a “gestalt” approach, and the rejection activity index (RAI) of each component of TCMR as described in revised Banff 2016 guidelines. Methods. Liver biopsies (n = 90) taken from patients who underwent LT in 2015 and 2016 at the Australian National Liver Transplant Unit were identified from the electronic medical records. All biopsy slides were microscopically graded by at least two assessors independently using the revised 2016 Banff criteria. Data were analysed using IBM SPSS v21. A Fisher–Freeman–Halton test was performed to assess the correlation between the global assessment and the RAI scores for each TCMR biopsy. Results. Within the cohort, 60 (37%, n = 164) patients underwent at least 1 biopsy within 12 months after LT. The most common biopsy outcome (total n = 90) was acute TCMR (64, 71.1%). Global assessment of TCMR slides strongly positively correlated with PI ( p value p value p value p value
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- 2023
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45. Educational Standards and Professional Capabilities for Radiographers in Infection Control
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Freihat, Rogayah, Lewis, Sarah, Jimenez, Yobelli, and Kench, Peter
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Medicine and Health Sciences ,Other Medicine and Health Sciences - Abstract
Scoping review of radiographers' education in infection prevention and control in medical imaging department.
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- 2022
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46. Scoping review protocol
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Freihat, Rogayah, Jimenez, Yobelli, Kench, Peter, and Lewis, Sarah
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- 2022
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47. Acinar cystic transformation of the pancreas
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William Cook, Charbel Sandroussi, Minh Truong, Raghwa Sharma, James Kench, and Catriona McKenzie
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Pathology and Forensic Medicine - Published
- 2023
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48. Association between vessels that encapsulate tumour clusters vascular pattern and hepatocellular carcinoma recurrence following liver transplantation
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Claude Dennis, David S. Prince, Leila Moayed-Alaei, Devika Remash, Emily Carr-Boyd, David G. Bowen, Simone I. Strasser, Michael Crawford, Carlo Pulitano, James Kench, Geoffrey W. McCaughan, Catriona McKenzie, and Ken Liu
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Cancer Research ,Oncology - Abstract
BackgroundVessels that encapsulate tumor clusters (VETC) is a novel vascular pattern seen on hepatocellular carcinoma (HCC) histology which has been shown to independently predict tumor recurrence and survival after liver resection. Its prognostic value in HCC patients receiving liver transplantation (LT) is unclear.MethodsWe retrospectively studied consecutive adults who underwent deceased-donor LT with active HCC found on explant between 2010-2019. Tumor tissue was stained for CD34 and quantified for VETC. Primary and secondary endpoints were time to recurrence (TTR) and recurrence-free survival (RFS).ResultsDuring the study period, 158 patients received LT where HCC was present on explant. VETC pattern was seen in 76.5% of explants. Patients with VETC-positive tumors spent longer on the waitlist (6.4 vs. 4.1 months, P=0.048), had higher median tumor numbers (2 vs. 1, P=0.001) and larger tumor sizes (20mm vs. 13mm, PP=0.001) and RFS (HR 1.267, P=0.014) after adjusting for other significant variables.ConclusionVETC pattern is commonly observed in HCC patients undergoing LT. The number of VETC-positive tumors, but not its presence, is an independent risk factor for TTR and RFS post-LT.
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- 2022
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49. Comprehensive methylome sequencing reveals prognostic epigenetic biomarkers for prostate cancer mortality
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Ruth Pidsley, Dilys Lam, Wenjia Qu, Timothy J. Peters, Phuc‐Loi Luu, Darren Korbie, Clare Stirzaker, Roger J. Daly, Phillip Stricker, James G. Kench, Lisa G. Horvath, and Susan J. Clark
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ADP Ribose Transferases ,Male ,Epigenome ,Humans ,Prostatic Neoplasms ,Sulfites ,Molecular Medicine ,Medicine (miscellaneous) ,DNA ,Prognosis ,Epigenesis, Genetic - Abstract
Prostate cancer is a clinically heterogeneous disease with a subset of patients rapidly progressing to lethal-metastatic prostate cancer. Current clinicopathological measures are imperfect predictors of disease progression. Epigenetic changes are amongst the earliest molecular changes in tumourigenesis. To find new prognostic biomarkers to enable earlier intervention and improved outcomes, we performed methylome sequencing of DNA from patients with localised prostate cancer and long-term clinical follow-up.We used whole-genome bisulphite sequencing (WGBS) to comprehensively map and compare DNA methylation of radical prostatectomy tissue between patients with lethal disease (n = 7) and non-lethal (n = 8) disease (median follow-up 19.5 years). Validation of differentially methylated regions (DMRs) was performed in an independent cohort (n = 185, median follow-up 15 years) using targeted multiplex bisulphite sequencing of candidate regions. Survival was assessed via univariable and multivariable analyses including clinicopathological measures (log-rank and Cox regression models).WGBS data analysis identified cancer-specific methylation patterns including CpG island hypermethylation, and hypomethylation of repetitive elements, with increasing disease risk. We identified 1420 DMRs associated with prostate cancer-specific mortality (PCSM), which showed enrichment for gene sets downregulated in prostate cancer and de novo methylated in cancer. Through comparison with public prostate cancer datasets, we refined the DMRs to develop an 18-gene prognostic panel. Applying this panel to an independent cohort, we found significant associations between PCSM and hypermethylation at EPHB3, PARP6, TBX1, MARCH6 and a regulatory element within CACNA2D4. Strikingly in a multivariable model, inclusion of CACNA2D4 methylation was a better predictor of PCSM versus grade alone (Harrell's C-index: 0.779 vs. 0.684).Our study provides detailed methylome maps of non-lethal and lethal prostate cancer and identifies novel genic regions that distinguish these patient groups. Inclusion of our DNA methylation biomarkers with existing clinicopathological measures improves prognostic models of prostate cancer mortality, and holds promise for clinical application.
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- 2022
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50. WHO classification of tumours fifth edition: Evolving issues in the classification, diagnosis and prognostication of prostate cancer
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Kench, James G, Amin, Mahul B, Berney, Daniel M, Compérat, Eva M, Cree, Ian A, Gill, Anthony J, Hartmann, Arndt, Menon, Santosh, Moch, Holger, Netto, George J, Raspollini, Maria R, Rubin, Mark A, Tan, Puay Hoon, Tsuzuki, Toyonori, Turjalic, Samra, van der Kwast, Theo H, Zhou, Ming, Srigley, John R, University of Zurich, and Kench, James G
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2734 Pathology and Forensic Medicine ,Signalling & Oncogenes ,10049 Institute of Pathology and Molecular Pathology ,Genome Integrity & Repair ,610 Medicine & health ,Tumour Biology ,2722 Histology ,Genetics & Genomics ,Computational & Systems Biology - Abstract
The 5th edition of the WHO Classification of Tumours of the Urinary and Male Genital Systems encompasses several updates to the classification and diagnosis of prostatic carcinoma as well as incorporating advancements in assessment of its prognosis, including recent grading modifications. Some of the salient aspects include: 1) recognition that PIN-like carcinoma is not synonymous with a pattern of ductal carcinoma but better classified as a subtype of acinar adenocarcinoma; 2) a specific section on treatment-related neuroendocrine prostatic carcinoma in view of the tight correlation between androgen deprivation therapy and the development of prostatic carcinoma with neuroendocrine morphology, and the emerging data on lineage plasticity; 3) a terminology change of basal cell carcinoma to “adenoid cystic (basal cell) cell carcinoma” given the presence of an underlying MYB::NFIB gene fusion in many cases; 4) discussion of the current issues in the grading of acinar adenocarcinoma and the prognostic significance of cribriform growth patterns; and 5) more detailed coverage of intraductal carcinoma of prostate (IDC-P) reflecting our increased knowledge of this entity, while recommending the descriptive term atypical intraductal proliferation (AIP) for lesions falling short of IDC-P but containing more atypia than typically seen in high-grade prostatic intraepithelial neoplasia (HGPIN). Lesions previously regarded as cribriform patterns of HGPIN are now included in the AIP category. This review discusses these developments, summarising the existing literature, as well as the emerging morphological and molecular data that underpins the classification and prognostication of prostatic carcinoma.
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- 2022
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