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)
Review
Oncology
Evgeny Imyanitov, Ekaterina Kuligina
Summary: Molecular genetic analysis plays a crucial role in colorectal cancer management, guiding treatment choices such as targeted therapies and immune checkpoint inhibitors. The emerging technologies of liquid biopsy and next-generation sequencing are revolutionizing the landscape of CRC molecular diagnosis.
WORLD JOURNAL OF GASTROINTESTINAL ONCOLOGY
(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
Gastroenterology & Hepatology
Pooja Dharwadkar, Garrett Greenan, Elena M. Stoffel, Ezra Burstein, Sara Pirzadeh-Miller, Sayoni Lahiri, Caitlin Mauer, Amit G. Singal, Caitlin C. Murphy
Summary: Racial/ethnic differences exist in referral to and receipt of germline genetic testing among young-onset CRC patients. These findings underscore the importance of universal genetic testing to address racial/ethnic disparities in young-onset CRC.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(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)
Article
Radiology, Nuclear Medicine & Medical Imaging
Xiaobo Chen, Lan He, Qingshu Li, Liu Liu, Suyun Li, Yuan Zhang, Zaiyi Liu, Yanqi Huang, Yun Mao, Xin Chen
Summary: This study established a robust radiomics signature based on CT to predict the microsatellite instability (MSI) status of colorectal cancer (CRC) patients. The signature showed robust performance in both internal and external validation cohorts and outperformed the clinical model. Additionally, the signature could stratify patients with stage II CRC according to prognosis.
EUROPEAN RADIOLOGY
(2023)
Article
Oncology
David J. Papke Papke Jr, Neal I. Lindeman, Deborah Schrag, J. Bryan Lorgulescu
Summary: Utilization of MMR/MSI testing has increased for advanced colorectal cancer patients, but there is still room for improvement. Testing rates lagged for older patients, those from the poorest households, and those managed at community cancer programs.
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2022)
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
A. Guyot D'Asnieres De Salins, G. Tachon, R. Cohen, L. Karayan-Tapon, A. Junca, E. Frouin, J. Godet, C. Evrard, V Randrian, A. Duval, M. Svrcek, O. Lascols, S. Vignot, F. Coulet, T. Andre, J-F Flejou, P. Cervera, D. Tougeron
Summary: The study confirmed a high degree of concordance between MSI and MMR IHC tests, emphasizing the importance of reviewing discordant cases and analysis by expert teams.
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
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
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.
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
Gastroenterology & Hepatology
Nora D. Hallensleben, Hester C. Timmerhuis, Robbert A. Hollemans, Sabrina Pocornie, Janneke van Grinsven, Sandra van Brunschot, Olaf J. Bakker, Rogier van der Sluijs, Matthijs P. Schwartz, Peter van Duijvendijk, Tessa Romkens, Martijn W. J. Stommel, Robert C. Verdonk, Marc G. Besselink, Stefan A. W. Bouwense, Thomas L. Bollen, Hjalmar C. van Santvoort, Marco J. Bruno
Summary: Cholecystectomy is recommended after an episode of acute biliary pancreatitis to prevent recurrent biliary events. In patients with necrotizing biliary pancreatitis, the optimal timing for surgery is within 8 weeks after discharge.
Article
Genetics & Heredity
Jose Garcia-Pelaez, Rita Barbosa-Matos, Celina Sao Jose, Sonia Sousa, Irene Gullo, Nicoline Hoogerbrugge, Fatima Carneiro, Carla Oliveira
Summary: Tumour risk syndromes (TRS) involve an increased risk of early-onset cancers in familial contexts, with some predisposition to diffuse gastric cancer explained by specific genes, while others remain genetically unsolved. Identifying heritable causes helps define diagnostic testing criteria and classify families for clinical management. The missing heritability in GC-associated TRS may involve a diversity of genes predisposing to other syndromes.
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2022)
Correction
Gastroenterology & Hepatology
Giorgio Lisi, Michela Campanelli, Maria Rosaria Mastrangeli, Domenico Spoletini, Rosa Menditto, Simona Grande, Massimiliano Boccuzzi, Michele Grande
INTERNATIONAL JOURNAL OF COLORECTAL DISEASE
(2022)
Article
Pathology
Elisabeth M. P. Steeghs, Geraldine R. Vink, Marloes A. G. Elferink, Quirinus J. M. Voorham, Hans Gelderblom, Iris D. Nagtegaal, Katrien Grunberg, Marjolijn J. L. Ligtenberg
Summary: The study in the Netherlands showed an increase in mutation testing rates for CRC patients over time, with anti-EGFR therapy mainly used in KRAS/NRAS wild-type patients after the third treatment line. The national average mutation rate was 63.9%, and NGS-based approaches detected more potential biomarkers.
JOURNAL OF CLINICAL PATHOLOGY
(2022)
Article
Pathology
Valentyna Kryklyva, Lodewijk A. A. Brosens, Monica A. J. Marijnissen-van Zanten, Marjolijn J. L. Ligtenberg, Iris D. Nagtegaal
Summary: The prevalence of dMMR in early-onset duodenal, ampullary, and pancreatic carcinomas was explored, with duodenal carcinomas showing the highest prevalence and most being associated with hereditary cancer syndromes. Universal dMMR testing is recommended in all early-onset duodenal, ampullary, and pancreatic carcinomas to determine the underlying hereditary condition.
JOURNAL OF PATHOLOGY CLINICAL RESEARCH
(2022)
Correction
Oncology
Peter H. J. Slootbeek, Iris S. H. Kloots, Minke Smits, Inge M. van Oort, Winald R. Gerritsen, Jack A. Schalken, Marjolijn J. L. Ligtenberg, Katrien Grunberg, Leonie I. Kroeze, Haiko J. Bloemendal, Niven Mehra
BRITISH JOURNAL OF CANCER
(2022)
Review
Genetics & Heredity
Linda A. J. Hendricks, Janneke Schuurs-Hoeijmakers, Isabel Spier, Maaike L. Haadsma, Astrid Eijkelenboom, Kirsten Cremer, Arjen R. Mensenkamp, Stefan Aretz, Janet R. Vos, Nicoline Hoogerbrugge
Summary: This article describes two cases of PTEN mosaicism, suggesting that it may be more common than currently reported. Awareness of PTEN mosaicism is crucial for timely diagnosis and inclusion in cancer surveillance programs, ultimately improving prognosis and life expectancy for affected individuals.
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2022)
Article
Oncology
Vera M. Witjes, Joze C. C. Braspenning, Nicoline Hoogerbrugge, Yvonne H. C. M. Smolders, Dorien M. A. Hermkens, Marian J. E. Mourits, Marjolijn J. L. Ligtenberg, Margreet G. E. M. Ausems, Joanne A. de Hullu
Summary: Universal tumor DNA testing in epithelial ovarian cancer patients can serve as an efficient pre-screening tool for hereditary cancer testing and guide treatment choices. However, implementing the Tumor-First workflow requires optimal multidisciplinary collaboration and detailed standardization.
Article
Oncology
Linda A. J. Hendricks, Nicoline Hoogerbrugge, Arjen R. Mensenkamp, Joan Brunet, Roser Lleuger-Pujol, Hildegunn Hoberg-Vetti, Marianne Tveit Haavind, Giovanni Innella, Daniela Turchetti, Stefan Aretz, Isabel Spier, Marc Tischkowitz, Arne Jahn, Thera P. Links, Maran J. W. Olderode-Berends, Ana Blatnik, Edward M. Leter, D. Gareth Evans, Emma R. Woodward, Verena Steinke-Lange, Violetta C. Anastasiadou, Chrystelle Colas, Marie-Charlotte Villy, Patrick R. Benusiglio, Anna Gerasimenko, Valeria Barili, Maud Branchaud, Claude Houdayer, Bianca Tesi, M. Omer Yazicioglu, Rachel S. van der Post, Janneke H. M. Schuurs-Hoeijmakers, Janet R. Vos, Liselotte P. van Hest, Muriel A. Adank, Floor Duijkers, Maartje Nielsen, Katja C. J. Verbeek, Yvette van Ierland, Jacques C. Giltay
Summary: PTEN Hamartoma Tumor Syndrome (PHTS) is a rare syndrome with a broad phenotypic spectrum, including increased risks of breast, endometrial, and thyroid cancer. This study aimed to provide more accurate and personalized cancer risks. The results showed that PHTS patients, especially females, have a significantly higher risk of breast, endometrial, and thyroid cancer.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2023)
Article
Oncology
Gerben Lassche, Sjoerd van Helvert, Astrid Eijkelenboom, Martijn J. H. Tjan, Erik A. M. Jansen, Patricia H. J. van Cleef, Gerald W. Verhaegh, Eveline J. Kamping, Katrien Grunberg, Adriana C. H. van Engen-van Grunsven, Marjolijn J. L. Ligtenberg, Carla M. L. van Herpen
Summary: This research aimed to assess the prevalence of actionable aberrations in salivary gland cancer (SGC) and identified several new gene fusions. Targets for genetically matched therapies were found in different SGC subtypes. This highlights the potential importance of molecular diagnostics in selecting systemic treatment for SGC.
Article
Oncology
Lisa S. M. Hofste, Maartje J. Geerlings, Daniel von Rhein, Sofie H. Tolmeijer, Marjan M. Weiss, Christian Gilissen, Tom Hofste, Linda M. Garms, Marcel J. R. Janssen, Heidi Rutten, Camiel Rosman, Rachel S. van der Post, Bastiaan R. Klarenbeek, Marjolijn J. L. Ligtenberg
Summary: Ultradeep sequencing-based detection of circulating tumor DNA in preoperative plasma of patients with locally advanced esophageal cancer can predict which patients have a high risk of recurrence after neoadjuvant chemoradiotherapy and surgery.
Article
Oncology
Lisa Elze, Rachel S. van der Post, Janet R. Vos, Arjen R. Mensenkamp, Mirjam S. C. de Hullu, Iris D. Nagtegaal, Nicoline Hoogerbrugge, Richarda M. de Voer, Marjolijn J. L. Ligtenberg
Summary: This study aims to assess whether other tumor types in individuals with Lynch syndrome share characteristics similar to colorectal and endometrial carcinomas. Analysis of the tumor history of 1745 individuals with Lynch syndrome revealed that more than half of the malignant tumors, apart from colorectal and endometrial carcinomas, exhibit microsatellite instability (MSI-H) and mismatch repair-deficiency (dMMR). Therefore, MSI-H/dMMR testing should be conducted for all malignancies in patients with Lynch syndrome when considering therapy with immune checkpoint inhibitors.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2023)
Article
Oncology
Peter H. J. Slootbeek, Joanneke K. Overbeek, Marjolijn J. L. Ligtenberg, Nielka P. van Erp, Niven Mehra
Summary: PARP inhibitors have shown great potential in the treatment of metastatic castration-resistant prostate cancer, with superior responses observed in patients with BRCA1 or BRCA2 gene mutations. Combination therapy with androgen receptor signaling inhibitors can prolong progression-free survival in HRRm patients, but has limited efficacy in the non-HRRm subgroup.