Article
Oncology
Xiaofan Lu, Yann Vano, Alexandra Helleux, Xiaoping Su, Veronique Lindner, Guillaume Davidson, Roger Mouawad, Jean-Philippe Spano, Morgan Roupre, Reza Elaidi, Eva Comperat, Virginie Verkarre, Chengming Sun, Christine Chevreau, Mostefa Bennamoun, Herve Lang, Thibault Tricard, Wenxuan Cheng, Li Xu, Irwin Davidson, Fangrong Yan, Wolf Herman Fridman, Catherine Sautes-Fridman, Stephane Oudard, Gabriel G. Malouf
Summary: This study identified a novel epigenetic phenotype associated with resistance to immune checkpoint inhibitors (ICIs) in clear-cell renal cell carcinomas (ccRCC). This phenotype, called TED, was found to be associated with sarcomatoid differentiation, poor clinical outcome and resistance to first-line ipilimumab-nivolumab combination therapy. TED exhibited specific epigenetic alterations, gene expression signatures and tumor microenvironment characteristics.
CLINICAL CANCER RESEARCH
(2023)
Article
Multidisciplinary Sciences
Elsie Cheruba, Ramya Viswanathan, Pui-Mun Wong, Howard John Womersley, Shuting Han, Brenda Tay, Yiting Lau, Anna Gan, Polly S. Y. Poon, Anders Skanderup, Sarah B. Ng, Aik Yong Chok, Dawn Qingqing Chong, Iain Beehuat Tan, Lih Feng Cheow
Summary: Genome-wide analysis of cell-free DNA methylation profile is a promising approach for sensitive and specific detection of many cancers. However, the high cost of whole-genome bisulfite sequencing makes it impractical for clinical translation. In this study, we developed a heat enrichment of CpG-rich regions for bisulfite sequencing (Heatrich-BS) platform, which allows for focused methylation profiling at a reduced sequencing cost suitable for frequent monitoring. Our method also enables tumor epigenetic subtyping and patient stratification. Heatrich-BS holds great potential for highly scalable screening and monitoring of cancer using liquid biopsy.
Article
Cell Biology
Junnan Liang, Tongtong Liu, Jingyu Liao, Lu Zhang, Mi Zhou, Weiqi Xu, Yi He, Guangzhen Cai, Guannan Jin, Jia Song, Ganxun Li, Huifang Liang, Zeyang Ding, Bixiang Zhang
Summary: The study identified a CIMP-related methylation signature specific for CCA (CMSC) that can classify patients into different risk groups and predict patient outcomes. Additionally, a subset of patients with an unfavorable prognosis correlated with CIMP-H was identified. Gene enrichment analysis suggested a potential mechanism of CIMP as a promoter of carcinogenesis by regulating proliferation.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Endocrinology & Metabolism
Pengfei Gu, Yu Zeng, Weike Ma, Wei Zhang, Yu Liu, Fengli Guo, Xianhui Ruan, Jiadong Chi, Xiangqian Zheng, Ming Gao
Summary: CpG island methylator phenotype (CIMP) plays an important role in papillary thyroid carcinomas (PTCs), being associated with higher malignancy and poor prognosis.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Biochemical Research Methods
Josephine Yates, Valentina Boeva
Summary: This study utilized a pan-cancer approach to define and explore CpG island methylator phenotype (CIMP) in 26 cancer types. The results confirmed the existence of CIMP in 19 cancers, showed its association with survival differences in eight cancer types, and identified potential drivers of CIMP. The study also found that CIMP was strongly correlated with tumor microenvironment characteristics.
BRIEFINGS IN BIOINFORMATICS
(2022)
Review
Oncology
Xiaofei Zhang, Wenjun Zhang, Pingan Cao
Summary: As the population ages in China, the incidence of colorectal cancer is on the rise, with CpG island methylator phenotype (CIMP) playing an important role in its development. Recent studies have shown a close relationship between CIMP and specific clinicopathological phenotypes and multiple molecular phenotypes in colorectal cancer. This paper introduces the latest progress on CIMP colorectal cancer in terms of chemotherapeutic drugs, targeted agents, and small molecular methylation inhibitors, aiming to provide potential clinical treatment strategies for personalized and precise treatment of colorectal cancer patients.
FRONTIERS IN ONCOLOGY
(2021)
Article
Gastroenterology & Hepatology
Rossella Tricarico, Jozef Madzo, Gabrielle Scher, Maya Cohen, Jaroslav Jelinek, Shinji Maegawa, Rajeswari Nagarathinam, Carly Scher, Wen-Chi Chang, Emmanuelle Nicolas, Michael Slifker, Yan Zhou, Karthik Devarajan, Kathy Q. Cai, Tim Kwok, Pamela Nakajima, Jinfei Xu, Pietro Mancuso, Valentina Doneddu, Luigi Bagella, Riley Williams, Siddharth Balachandran, Nicholas Maskalenko, Kerry Campbell, Xueying Ma, Israel Canadas, Julen Viana-Errasti, Victor Moreno, Laura Valle, Sergei Grivennikov, Iuliia Peshkova, Natalia Kurilenko, Aleksandra Mazitova, Ekaterina Koltsova, Hayan Lee, Martin Walsh, Reuben Duttweiler, Johnathan R. Whetstine, Timothy J. Yen, Jean-Pierre Issa, Alfonso Bellacosa
Summary: Aberrant DNA methylation is common in colorectal cancer (CRC), but the underlying mechanisms and pathological consequences are not well understood. In this study, disruption of the Tet1 and/or Tdg genes in mice resulted in increased size and invasive features of colonic adenomas. Furthermore, Tet1 and Tdg mutations led to global DNA hypomethylation and CpG island hypermethylation in colonic adenomas. The mutations also upregulated inflammatory, immune, and interferon response genes.
Article
Pathology
Lina Irshaid, Danielle C. Costigan, Fei Dong, Ursula A. Matulonis, Marisa R. Nucci, David L. Kolin
Summary: This study aimed to characterize the genetic landscape of Mullerian clear cell carcinoma (CCC) and correlate these findings with clinicopathologic features. The results showed that the genetic landscape of CCC is complex, with ARID1A and PIK3CA being the most frequently mutated genes. Furthermore, CCC can be classified into different molecular subgroups, which have different prognostic implications.
Article
Oncology
Laura Libera, Giorgia Ottini, Nora Sahnane, Fabiana Pettenon, Mario Turri-Zanoni, Alessia Lambertoni, Anna Maria Chiaravalli, Federico Leone, Paolo Battaglia, Paolo Castelnuovo, Silvia Uccella, Daniela Furlan, Carla Facco, Fausto Sessa
Summary: This study performed histopathological, immunohistochemical, and molecular analyses on PDSNCs, revealing a correlation between SWI/SNF complex and IDH2 defects and abnormal methylation levels, which were associated with a worse prognosis.
Article
Oncology
Claudia Manini, Estibaliz Lopez-Fernandez, Jose Lopez
Summary: Intratumor heterogeneity (ITH) is a common event in malignant tumors and is a major cause of therapeutic failures in modern oncology. Clear cell renal cell carcinoma (CCRCC) exemplifies ITH. To accurately detect ITH, appropriate tumor sampling is necessary. We propose a personalized multisite tumor sampling (pMSTS) strategy based on the regionalization patterns of ITH, with a focus on sampling the high-ITH peripheral zones of the tumor.
Article
Psychiatry
Sheila T. Nagamatsu, Gregory Rompala, Yasmin L. Hurd, Diana L. Nunez-Rios, Janitza L. Montalvo-Ortiz
Summary: This study investigates the role of mCpHs in OUD and identifies important biological pathways and drug targets associated with the disorder in the human postmortem orbital frontal cortex.
FRONTIERS IN PSYCHIATRY
(2023)
Article
Multidisciplinary Sciences
Sujun Chen, Jessica Petricca, Wenbin Ye, Jiansheng Guan, Yong Zeng, Nicholas Cheng, Linsey Gong, Shu Yi Shen, Junjie T. Hua, Megan Crumbaker, Michael Fraser, Stanley Liu, Scott Bratman, Theodorus van der Kwast, Trevor Pugh, Anthony M. Joshua, Daniel D. De Carvalho, Kim N. Chi, Philip Awadalla, Guoli Ji, Felix Feng, Alexander W. Wyatt, Housheng Hansen He
Summary: The authors used cell-free DNA methylation analysis to demonstrate changes in hypermethylation in metastatic prostate cancer, and its impact on immune features and clinical outcomes. The results showed that the cell-free DNA methylome can capture variations beyond the tumor, and has a high accuracy in predicting disease types.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Ian S. Hagemann, Wei Deng, Richard J. Zaino, Matthew A. Powell, Camille Gunderson Jackson, Casey Cosgrove, Cara Mathews, Michael L. Pearl, Steven Waggoner, Rahel Ghebre, Shashikant Lele, Saketh Guntupalli, Angeles Alvarez Secord, Olga Ioffe, Golnar Rasty, Meenakshi Singh, Robert Soslow, William Creasman, David G. Mutch
Summary: This study aimed to investigate the differences in stage at diagnosis, initial pattern of spread, and patient survival between mixed clear cell carcinoma and pure clear cell carcinoma. The results showed that the presence of mixed endometrioid or serous components in clear cell carcinoma did not correlate with a significant difference in prognosis. Patients with indeterminate clear cell/endometrioid features had better prognosis.
GYNECOLOGIC ONCOLOGY
(2023)
Article
Gastroenterology & Hepatology
Li Lu, Jiao Fan, Weijue Xu, Xiaoming Cui, Shaohua Hu, Ting Guo, Zhibao Lv
Summary: Epigenetic changes in the form of DNA methylation were found in intestinal tissue of human NEC patients, with a significant reduction in DNMT3A expression. Genome-wide DNA methylation analysis revealed lower CG methylation levels in unique regions of NEC compared with controls. Differential methylated regions (DMRs) associated with intestinal permeability, platelet aggregation, and lymphocyte proliferation were identified, with specific genes involved in lymphocyte regulation showing hypermethylation and downregulation. These findings suggest a potential link between epigenetic changes and lymphocyte regulation in human NEC, with implications for potential diagnostics and therapies.
DIGESTIVE DISEASES AND SCIENCES
(2022)
Article
Genetics & Heredity
Xiangyu Che, Jianyi Li, Yingkun Xu, Qifei Wang, Guangzhen Wu
Summary: This study reveals the association between clear cell renal cell carcinoma (ccRCC) and changes in the TGF-beta signaling pathway. Transcriptome analysis identified several genes related to ccRCC prognosis and established a prognostic model. Grouping ccRCC patients based on TGF-beta scores is crucial for evaluating prognosis, selecting targeted drugs, and identifying new therapeutic targets.
FRONTIERS IN GENETICS
(2022)