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)
Editorial Material
Cell Biology
Gayathri Anandappa, Michael J. Overman
Summary: In a recent study, Amodio and colleagues discovered a method to modulate immunosurveillance in colorectal tumors by manipulating DNA mismatch repair heterogeneity. They found that enriching the MMR deficient component using 6-thioguanine can improve tumor control in murine models.
CELL REPORTS MEDICINE
(2023)
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)
Article
Multidisciplinary Sciences
Inas Elsayed, Robert Geraghty, Salwa O. Mekki, Ahmed A. Mohamedani, Susan Ahern, Omer E. H. Salim, Balgis B. M. Khalil, Sawsan Abdelrahim, Suliman H. Suliman, Moawia M. A. Elhassan, Salah O. Salah, Mohamed E. Salih, Abubakr H. Widatalla, Osman S. Abdelhamed, Xiaosheng Wang, Eanna J. Ryan, Des Winter, Salih Bakhiet, Kieran Sheahan
Summary: There is a significant clinical need for molecular pathology services for colorectal cancer in Sudan. In this study, researchers aimed to introduce a molecular genetic service for colorectal cancer in Sudan and explore the molecular features and their relationship to patient survival and clinicopathological characteristics. They found that a subtype of mismatch repair deficient colorectal cancer was present in 16% of cases, and a presumptive diagnosis of Lynch Syndrome was made in 14% of patients. The study also revealed a high mortality rate in Sudanese colorectal cancer patients, which was correlated with advanced disease stage and mismatch repair status.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Kuo-Hsing Chen, Liang-In Lin, Chang-Tsu Yuan, Li-Hui Tseng, Yu-Liang Chao, Yi-Hsin Liang, Jin-Tung Liang, Been-Ren Lin, Ann-Lii Cheng, Kun-Huei Yeh
Summary: In Taiwan, distinct clinicopathological features were identified for CIMP-high CRC among different age groups. Our data suggest the association between BMI >= 27.5 kg/m(2) and CIMP-high CRC in patients younger than 50 years.
BRITISH JOURNAL OF CANCER
(2021)
Review
Oncology
Dedrick Kok Hong Chan, Simon James Alexander Buczacki
Summary: Colorectal cancer is a global burden, characterized by an initial explosion of genetic diversity followed by neutral dynamics. Understanding the interplay between clonal populations during neutral evolution provides insights into the roles of driver genes in the progression from normal colonic epithelium to adenoma and carcinoma. Recent advances have focused on genetic, transcriptomic, and proteomic factors, as well as the ecological and evolutionary processes that contribute to cancer development.
Review
Gastroenterology & Hepatology
Lourdes Pilar Chavez-Hidalgo, Silvia Martin-Fernandez-de-Labastida, Marian M. de Pancorbo, Marta Arroyo-Izaga
Summary: The influence of dietary methyl donors on DNA methylation during colorectal cancer (CRC) carcinogenesis may be modified by polymorphisms in epigenetic regulators.
WORLD JOURNAL OF GASTROENTEROLOGY
(2023)
Review
Immunology
Wei-Jian Mei, Mi Mi, Jing Qian, Nan Xiao, Ying Yuan, Pei-Rong Ding
Summary: Colorectal cancers with high microsatellite instability and deficient mismatch repair have different characteristics compared to normal CRC, but the testing rates for MSI and MMR remain low in clinical practice. Insufficient testing fails to identify patients with these types of CRC who could benefit from immunotherapy. Understanding the importance of MMR/MSI status in the clinical characteristics and prognosis of CRC may help improve testing rates and guide the development of more effective therapies.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Sophia J. Wagner, Daniel Reisenbuechler, Nicholas P. West, Jan Moritz Niehues, Jiefu Zhu, Sebastian Foersch, Gregory Patrick Veldhuizen, Philip Quirke, Heike I. Grabsch, Piet A. van den Brandt, Gordon G. A. Hutchins, Susan D. Richman, Tanwei Yuan, Rupert Langer, Josien C. A. Jenniskens, Kelly Offermans, Wolfram Mueller, Richard Gray, Stephen B. Gruber, Joel K. Greenson, Gad Rennert, Joseph D. Bonner, Daniel Schmolze, Jitendra Jonnagaddala, Nicholas J. Hawkins, Robyn L. Ward, Dion Morton, Matthew Seymour, Laura Magill, Marta Nowak, Jennifer Hay, Viktor H. Koelzer, David N. Church, Christian Matek, Carol Geppert, Chaolong Peng, Cheng Zhi, Xiaoming Ouyang, Jacqueline A. James, Maurice B. Loughrey, Manuel Salto-Tellez, Hermann Brenner, Michael Hoffmeister, Daniel Truhn, Julia A. Schnabel, Melanie Boxberg, Tingying Peng, Jakob Nikolas Kather
Summary: This study develops a new transformer-based pipeline for predicting prognostic biomarkers from colorectal cancer pathology slides. The results show that this approach significantly improves performance, generalizability, data efficiency, and interpretability compared to current algorithms. The method also solves a longstanding diagnostic problem by achieving clinical-grade performance on endoscopic biopsy tissue.
Article
Oncology
Muhammad G. Kibriya, Maruf Raza, Mohammed Kamal, Zahidul Haq, Rupash Paul, Andrew Mareczko, Brandon L. Pierce, Habibul Ahsan, Farzana Jasmine
Summary: In this study, we compared tumor and adjacent normal tissue samples from 165 colorectal carcinoma patients and found that the tumor tissue had shorter relative telomere length (RTL). This RTL shortening was observed regardless of age group, gender, tumor pathology, and microsatellite instability (MSI) status. Additionally, we discovered that RTL shortening was more pronounced in low-grade CRC and in the presence of MSI. Furthermore, our research revealed that RTL shortening in CRC was associated with the upregulation of DNA replication genes and cyclin dependent-kinase genes, as well as the downregulation of caspase executor, reducing apoptosis.
Article
Multidisciplinary Sciences
Olusegun Isaac Alatise, Gregory C. Knapp, Avinash Sharma, Walid K. Chatila, Olukayode A. Arowolo, Olalekan Olasehinde, Olusola C. Famurewa, Adeleye D. Omisore, Akinwumi O. Komolafe, Olaejinrinde O. Olaofe, Aba I. Katung, David E. Ibikunle, Adedeji A. Egberongbe, Samuel A. Olatoke, Sulaiman O. Agodirin, Olusola A. Adesiyun, Ademola Adeyeye, Oladapo A. Kolawole, Akinwumi O. Olakanmi, Kanika Arora, Jeremy Constable, Ronak Shah, Azfar Basunia, Brooke Sylvester, Chao Wu, Martin R. Weiser, Ken Seier, Mithat Gonen, Zsofia K. Stadler, Yelena Kemel, Efsevia Vakiani, Michael F. Berger, Timothy A. Chan, David B. Solit, Jinru Shia, Francisco Sanchez-Vega, Nikolaus Schultz, Murray Brennan, J. Joshua Smith, T. Peter Kingham
Summary: Understanding the molecular and phenotypic profile of colorectal cancer (CRC) in West Africa is crucial for addressing the rising burden of disease, as shown by a study comparing Nigerian CRC patients to those from TCGA and MSKCC. High microsatellite instability, differences in genetic mutations, and presentation characteristics suggest a unique biology of CRC in Nigeria that requires tailored diagnostic and treatment approaches.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Satoshi Fujii, Daisuke Kotani, Masahiro Hattori, Masato Nishihara, Toshihide Shikanai, Junji Hashimoto, Yuki Hama, Takuya Nishino, Mizuto Suzuki, Ayatoshi Yoshidumi, Makoto Ueno, Yoshito Komatsu, Toshiki Masuishi, Hiroki Hara, Taito Esaki, Yoshiaki Nakamura, Hideaki Bando, Tomoyuki Yamada, Takayuki Yoshino
Summary: This study utilized deep learning techniques to extract pathomorphologic features from tissue section images, enabling the accurate prediction of genetic abnormalities in cancer. The results demonstrated high accuracy of this method and its potential for predicting genetic abnormalities without the need for gene tests.
CLINICAL CANCER RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Marta Mendiola, Victoria Heredia-Soto, Ignacio Ruz-Caracuel, Amparo Baillo, Jorge Luis Ramon-Patino, Francisco Javier Escudero, Maria Miguel, Alberto Pelaez-Garcia, Alicia Hernandez, Jaime Feliu, David Hardisson, Andres Redondo
Summary: This study aimed to establish and compare different approaches for assessing the MMR status in endometrial carcinomas. A total of 126 early-stage EC samples were analyzed using immunohistochemistry, PCR-based MSI, methylation-specific multiplex ligation-dependent probe amplification, and targeted next-generation sequencing. The study found that approximately 53.2% of the samples were MMR deficient, while 46.8% were MMR proficient. Additionally, 44.3% of the samples showed genetic or epigenetic alterations, with MLH1 promoter methylation being the most common event.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pathology
Huu-Giao Nguyen, Oxana Lundstroem, Annika Blank, Heather Dawson, Alessandro Lugli, Maria Anisimova, Inti Zlobec
Summary: This study investigated the association between CMS classification and mucin-to-tumor area using a deep learning algorithm, and explored the expression of specific mucins in predicting CMS groups and clinical outcomes. The inter-observer agreement between pathologists' scores and the algorithm was excellent. The absence of mucin-expressing tumors in CMS2 provides an important phenotype-genotype correlation, and MUC5AC protein expression correlated with aggressive tumor features.
Review
Oncology
Nuria Mulet-Margalef, Jenniffer Linares, Jordi Badia-Ramentol, Mireya Jimeno, Carolina Sanz Monte, Jose Luis Manzano Mozo, Alexandre Calon
Summary: About 5-15% of colorectal cancers have deficiencies in mismatch repair machinery and high microsatellite instability (dMMR/MSI-H), rendering the tumor immune microenvironment more susceptible to immunotherapy. While immunomodulating drugs have improved treatment for dMMR/MSI-H CRC patients, there is a significant portion that shows resistance due to unknown molecular traits. This review discusses the current understanding of dMMR/MSI-H CRC and its therapeutic implications, as well as efforts to identify resistance mechanisms and predictive biomarkers.
Article
Oncology
Andrew Bakshi, Yin Cao, Suzanne G. Orchard, Prudence R. Carr, Amit D. Joshi, Alisa K. Manning, Daniel D. Buchanan, Asad Umar, Ingrid M. Winship, Peter Gibbs, John R. Zalcberg, Finlay Macrae, John J. McNeil, Paul Lacaze, Andrew T. Chan
Summary: Although aspirin has been considered a potential preventive agent for colorectal cancer, recent data suggest it may not be beneficial for older individuals. This study investigated the association between genetic susceptibility to colorectal cancer and aspirin use in a cohort of older individuals, and found that while genetic risk was associated with an increased risk of colorectal cancer, aspirin use did not reduce the incidence of the disease.
CANCER PREVENTION RESEARCH
(2022)
Article
Oncology
Sophia Harlid, Bethany Van Guelpen, Conghui Qu, Bjorn Gylling, Elom K. Aglago, Efrat L. Amitay, Hermann Brenner, Daniel D. Buchanan, Peter T. Campbell, Yin Cao, Andrew T. Chan, Jenny Chang-Claude, David A. Drew, Jane C. Figueiredo, Amy J. French, Steven Gallinger, Marios Giannakis, Graham G. Giles, Marc J. Gunter, Michael Hoffmeister, Li Hsu, Mark A. Jenkins, Yi Lin, Victor Moreno, Neil Murphy, Polly A. Newcomb, Christina C. Newton, Jonathan A. Nowak, Mireia Obon-Santacana, Shuji Ogino, John D. Potter, Mingyang Song, Robert S. Steinfelder, Wei Sun, Stephen N. Thibodeau, Amanda E. Toland, Tomotaka Ugai, Caroline Y. Um, Michael O. Woods, Amanda Phipps, Tabitha Harrison, Ulrike Peters
Summary: This study confirms the established association between diabetes and colorectal cancer risk, and suggests that it particularly increases the risk of BRAF-mutated tumors.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Article
Genetics & Heredity
Kathleen Anne Bell, Raymond Kim, Melyssa Aronson, Brittany Gillies, Arif Ali Awan, Kathy Chun, Jennifer Hart, Rachel Healey, Linda Kim, Goran Klaric, Karen Panabaker, Peter J. B. Sabatini, Bekim Sadikovic, Shamini Selvarajah, Amanda C. Smith, Tracy L. Stockley, Andrea K. Vaags, Andrea Eisen, Aaron Pollett, Harriet Feilotter
Summary: Ontario has achieved standardization and coordination of cancer genetic testing across the province through the development of a standardized cancer gene list and eligibility criteria for hereditary cancer testing.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Oncology
Pierre-Antoine Dugue, Chenglong Yu, Allison M. M. Hodge, Ee Ming Wong, JiHoon E. E. Joo, Chol-Hee Jung, Daniel Schmidt, Enes Makalic, Daniel D. D. Buchanan, Gianluca Severi, Dallas R. R. English, John L. L. Hopper, Roger L. L. Milne, Graham G. G. Giles, Melissa C. C. Southey
Summary: Methylation marks can be useful markers of cancer risk, capturing current and past exposures better than questionnaires and reflecting individual responses to exposure. This study used data from case-control studies to examine the association between blood DNA methylation and risk of various cancers. Methylation scores for smoking, BMI, and alcohol consumption were calculated and found to have independent associations with cancer risk, providing some improvements in risk prediction.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Oncology
John Lai, Chi Kuen Wong, Daniel F. Schmidt, Miroslaw K. Kapuscinski, Karen Alpen, Robert J. Macinnis, Daniel D. Buchanan, Aung K. Win, Jane C. Figueiredo, Andrew T. Chan, Tabitha A. Harrison, Michael Hoffmeister, Emily White, Loic Le Marchand, Rish K. Pai, Ulrike Peters, John L. Hopper, Mark A. Jenkins, Enes Makalic
Summary: The DEPTH analysis method can be used to identify candidate susceptibility regions for colorectal cancer, and it has identified regions that conventional analyses cannot detect in larger datasets. DEPTH identified many new candidate susceptibility regions in the CCFR and GECCO studies, and it found four reproducible regions.
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2023)
Article
Oncology
Andrei-Emil Constantinescu, Caroline J. Bull, Nicholas Jones, Ruth Mitchell, Kimberley Burrows, Niki Dimou, Stephane Bezieau, Hermann Brenner, Daniel D. Buchanan, Mauro D'Amato, Mark A. Jenkins, Victor Moreno, Rish K. Pai, Caroline Y. Um, Emily White, Neil Murphy, Marc Gunter, Nicholas J. Timpson, Jeroen R. Huyghe, Emma E. Vincent
Summary: Observational studies have shown that eosinophils may protect against colorectal cancer (CRC) development, while neutrophils may be implicated in its risk. This study used Mendelian randomisation (MR) to estimate the causal effect of circulating white blood cell (WBC) counts, specifically basophils, eosinophils, monocytes, lymphocytes, and neutrophils, on CRC risk. The results suggest that increased basophil and eosinophil counts are protective against CRC, and increased lymphocyte count may also have a protective effect.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Letter
Oncology
Pierre-Antoine Dugue, Chenglong Yu, Allison M. M. Hodge, Ee Ming Wong, JiHoon E. E. Joo, Chol-Hee Jung, Daniel Schmidt, Enes Makalic, Daniel D. D. Buchanan, Gianluca Severi, Dallas R. R. English, John L. L. Hopper, Roger L. L. Milne, Graham G. G. Giles, Melissa C. C. Southey
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Oncology
Romy Walker, Khalid Mahmood, Julia Como, Mark Clendenning, Jihoon E. Joo, Peter Georgeson, Sharelle Joseland, Susan G. Preston, Bernard J. Pope, James M. Chan, Rachel Austin, Jasmina Bojadzieva, Ainsley Campbell, Emma Edwards, Margaret Gleeson, Annabel Goodwin, Marion T. Harris, Emilia Ip, Judy Kirk, Julia Mansour, Helen Mar Fan, Cassandra Nichols, Nicholas Pachter, Abiramy Ragunathan, Allan Spigelman, Rachel Susman, Michael Christie, Mark A. Jenkins, Rish K. Pai, Christophe Rosty, Finlay A. Macrae, Ingrid M. Winship, Daniel D. Buchanan, ANGELS Study
Summary: This study examined the effectiveness of Lynch syndrome-specific tumor features in classifying MMR gene variants of uncertain clinical significance. The findings confirmed that identifying these features can improve the classification of MMR variants and enable optimal clinical care.
Letter
Gastroenterology & Hepatology
Khalid Mahmood, Minta Thomas, Conghui Qu, Li Hsu, Daniel D. Buchanan, Ulrike Peters
Article
Oncology
Essa Al-Mansor, Meghan Mahoney, Maxime Chenard-Poirier, Ravi Ramjeesingh, Vimoj Nair, Erin Kennedy, Gordon Locke, Stephen Welch, Scott Berry, Felix Couture, Elena Elimova, Aaron Pollett, Aamer Mahmud, Brooke Wilson, Dawn Armstrong, Conrad Falkson, Timothy Asmis, Michael Vickers, Rachel Goodwin
Summary: The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2023 aimed to develop consensus statements on emerging and evolving treatment paradigms. Participants included medical oncologists and surgical oncologists from Canada, who reviewed reports and literature to reach consensus opinions.
Meeting Abstract
Oncology
Soyoun Rachel Kim, Ilias Ettayebi, Gabrielle Trepanier, Lucy Zhao, Emily Van De laar, Espin-Garcia Osvaldo, Aaron Pollett, Lua Eiriksson, Kathy Han, Sarah Ferguson
INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
(2022)
Meeting Abstract
Oncology
Soyoun Rachel Kim, Ilias Ettayebi, Gabrielle Trepanier, Lucy Zhao, Emily Van de Laar, Osvaldo Espin-Garcia, Aaron Pollett, Lua Eiriksson, Kathy Han, Sarah Ferguson
GYNECOLOGIC ONCOLOGY
(2022)
Meeting Abstract
Oncology
Soyoun Rachel Kim, Leslie Oldfield, Osvaldo Espin-Garcia, Kathy Han, Danielle Vicus, Lua Eiriksson, Alicia Tone, Aaron Pollett, Emily Van de Laar, Stephanie Pedersen, Johanna Wellum, Marcus Bernardini, Trevor Pugh, Sarah Ferguson
GYNECOLOGIC ONCOLOGY
(2022)
Meeting Abstract
Medicine, Research & Experimental
Boris Virine, Aaron Pollett
LABORATORY INVESTIGATION
(2022)
Meeting Abstract
Pathology
Boris Virine, Aaron Pollett
