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
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)
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
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)
Review
Biochemistry & Molecular Biology
Karpinski Pawel, Sasiadek Maria Malgorzata
Summary: The CpG island methylator phenotype (CIMP) is an important manifestation of epigenetic instability in cancer. It has been extensively studied in various tumor types, but its use as a diagnostic marker and therapeutic target in solid tumors is limited by the lack of generalizability and reproducibility of epigenetic markers, as well as its poor predictive value in clinical outcomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Lila Zhu, Xinyu Li, Ying Yuan, Caixia Dong, Mengyuan Yang
Summary: The APC gene, known as a tumor suppressor gene, has two promoters 1A and 1B. Research on APC has mainly focused on its loss-of-function variants causing familial adenomatous polyposis. However, hypermethylation of the APC CpG sequence is also associated with carcinogenesis in various cancers, especially in gastrointestinal tumors.
FRONTIERS IN ONCOLOGY
(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
Biology
Alexander Joschua Ohnmacht, Anantharamanan Rajamani, Goeksu Avar, Ginte Kutkaite, Emanuel Goncalves, Dieter Saur, Michael Patrick Menden
Summary: A comprehensive analysis of different types of cancer reveals epigenetic drug response biomarkers, including differentially methylated sites, genetic, epigenetic, and transcriptomic datasets. Aberrant DNA methylation is associated with genetic alterations and plays a role in cancer-related transcriptional deregulation. This study analyzes 721 cancer cell lines from 22 cancer types treated with 453 anti-cancer compounds, identifying 19 DNA methylation biomarkers across five cancer types and 17 drugs. DNA methylation acts as a predictive biomarker by regulating the expression of proximal genes, thereby enhancing biological signals across multi-omics data modalities. Notably, the study also uncovers the potential sensitivity of melanoma to a specific inhibitor through NEK9 promoter hypermethylation-induced downregulation of NEK9. Overall, epigenomics has the potential to improve patient stratification and facilitate precision oncology.
COMMUNICATIONS BIOLOGY
(2023)
Article
Oncology
Jennifer A. Karlow, Siddhartha Devarakonda, Xiaoyun Xing, Hyo Sik Jang, Ramaswamy Govindan, Mark Watson, Ting Wang
Summary: This study identified recurrent methylation patterns in brain metastases of non-small cell lung cancer (NSCLC), which may serve as prognostic biomarkers and contribute to disease progression. The altered DNA methylation was associated with the loss of EZH2 occupancy at developmental genes and changes in epigenetic regulation.
Article
Multidisciplinary Sciences
Buze Chen, Xiaojuan Ding, Ailing Wan, Xin Qi, Xiaoman Lin, Haihong Wang, Wenyu Mu, Gang Wang, Junnian Zheng
Summary: TLX2 plays an important role in multiple tumors and its abnormal expression is associated with a poor overall survival rate in several cancer types. The most common type of alteration in TLX2 is amplification, and it co-occurs with alterations in other genes. TLX2 has high methylation levels in various tumors. Its expression is related to immune infiltration, immune checkpoint genes, and chemoresistance.
SCIENTIFIC REPORTS
(2023)
Article
Oncology
Jaqueline Loaeza-Loaeza, Berenice Illades-Aguiar, Oscar del Moral-Hernandez, Yaneth Castro-Coronel, Marco A. Leyva-Vazquez, Roberto Dircio-Maldonado, Julio Ortiz-Ortiz, Daniel Hernandez-Sotelo
Summary: This study analyzed the methylation of 8 genes involved in maintaining cell normality and found that high CIMP is significantly associated with the risk of HSIL and CC.
CLINICAL EPIGENETICS
(2022)
Article
Dermatology
Kathleen Conway, Yihsuan S. Tsai, Sharon N. Edmiston, Joel S. Parker, Eloise A. Parrish, Honglin Hao, Pei Fen Kuan, Glynis A. Scott, Jill S. Frank, Paul Googe, David W. Ollila, Nancy E. Thomas
Summary: The study found that CIMP melanoma is associated with age, melanoma classification, and ulceration, and has a lower survival rate. CIMP melanoma exhibits hypermethylation of genes important in tumor progression and immunity, contradicting the fact that it occurs in early melanoma.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Oncology
Harumi Yamada, Hideyuki Takeshima, Ryoji Fujiki, Satoshi Yamashita, Shigeki Sekine, Takayuki Ando, Naoko Hattori, Atsushi Okabe, Takaki Yoshikawa, Kazutaka Obama, Hitoshi Katai, Atsushi Kaneda, Toshikazu Ushijima
Summary: The CpG island methylator phenotype (CIMP) is associated with prognosis and drug sensitivity in multiple cancer types. This study demonstrates that mutations in the SWI/SNF chromatin remodeling complex, particularly ARID1A, are associated with CIMP induction in gastric cancer, as well as in uterine endometrial and colorectal cancers. The loss of ARID1A function causes aberrant DNA methylation and is likely a potential mechanism for CIMP induction.
Article
Endocrinology & Metabolism
Pavlos Fanis, Maria Morrou, Marios Tomazou, Kyriaki Michailidou, George M. M. Spyrou, Meropi Toumba, Nicos Skordis, Vassos Neocleous, Leonidas A. A. Phylactou
Summary: Makorin RING finger protein 3 (MKRN3) is an important factor associated with Prader-Willi syndrome. It is expressed in the hypothalamus and mutations in the gene have been found in patients with central precocious puberty. The methylation status of the Mkrn3 promoter was investigated in female mice and differential methylation patterns were observed between pre-pubertal and pubertal/post-pubertal stages.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Multidisciplinary Sciences
Yu-Hsin Chu, Yi-Chen Huang, Pei-Yun Chiu, Wen-Hung Kuo, Yan-Ru Pan, Yuan-Ting Kuo, Rong-Hsuan Wang, Yu-Chin Kao, Yi-Hsiang Wang, Yi-Fan Lin, Kai-Ti Lin
Summary: Breast cancer is a leading cause of cancer-related death in women, and triple-negative breast cancer (TNBC) is a particularly aggressive subtype. Using bioinformatic approaches, researchers found that the microRNA-708 promoter is highly methylated in breast carcinomas, which is associated with a poor prognosis. By combining the hypomethylating agent decitabine with a synthetic glucocorticoid, they were able to increase the expression of microRNA-708 and suppress breast cancer cell proliferation, migration, and invasion in TNBC patients.
Article
Oncology
Sebastian Mondaca, Matthew Margolis, Francisco Sanchez-Vega, Philip Jonsson, Jamie C. Riches, Geoffrey Y. Ku, Jaclyn F. Hechtman, Yaelle Tuvy, Michael F. Berger, Manish A. Shah, David P. Kelsen, David H. Ilson, Kenneth Yu, Zoe Goldberg, Andrew S. Epstein, Avni Desai, Vincent Chung, Joanne F. Chou, Marinela Capanu, David B. Solit, Nikolaus Schultz, Yelena Y. Janjigian
Article
Oncology
Michael Offin, Hira Rizvi, Megan Tenet, Andy Ni, Francisco Sanchez-Vega, Bob T. Li, Alexander Drilon, Mark G. Kris, Charles M. Rudin, Nikolaus Schultz, Maria E. Arcila, Marc Ladanyi, Gregory J. Riely, Helena Yu, Matthew D. Hellmann
CLINICAL CANCER RESEARCH
(2019)
Article
Biochemistry & Molecular Biology
Di Huang, Hanna M. Petrykowska, Brendan F. Miller, Laura Elnitski, Ivan Ovcharenko
Editorial Material
Genetics & Heredity
Marc Ladanyi, Francisco Sanchez Vega, Marjorie Zauderer
Article
Genetics & Heredity
Valer Gotea, Gennady Margolin, Laura Elnitski
Article
Biology
Jianing Xu, Ed Reznik, Ho-Joon Lee, Gunes Gundem, Philip Jonsson, Judy Sarungbam, Anna Bialik, Francisco Sanchez-Vega, Chad J. Creighton, Jake Hoekstra, Li Zhang, Peter Sajjakulnukit, Daniel Kremer, Zachary Tolstyka, Jozefina Casuscelli, Steve Stirdivant, Jie Tang, Nikolaus Schultz, Paul Jeng, Yiyu Dong, Wenjing Su, Emily H. Cheng, Paul Russo, Jonathan A. Coleman, Elli Papaemmanuil, Ying-Bei Chen, Victor E. Reuter, Chris Sander, Scott R. Kennedy, James J. Hsieh, Costas A. Lyssiotis, Satish K. Tickoo, A. Ari Hakimi
Article
Genetics & Heredity
Stephen M. Mount, Ziga Avsec, Liran Carmel, Rita Casadio, Muhammed Hasan Celik, Ken Chen, Jun Cheng, Noa E. Cohen, William G. Fairbrother, Tzila Fenesh, Julien Gagneur, Valer Gotea, Tamar Holzer, Chiao-Feng Lin, Pier Luigi Martelli, Tatsuhiko Naito, Thi Yen Duong Nguyen, Castrense Savojardo, Ron Unger, Robert Warig, Yuedong Yang, Huiying Zhao
Article
Hematology
Andrew Dunbar, Kelly L. Bolton, Sean M. Devlin, Francisco Sanchez-Vega, Jianjiong Gao, Jodi Mones, Jonathan Wills, Daniel Kelly, Mirko Farina, Keith B. Cordner, Young Park, Sirish Kishore, Krishna Juluru, Neil M. Iyengar, Ross L. Levine, Ahmet Zehir, Wungki Park, Alok A. Khorana, Gerald A. Soff, Simon Mantha
Summary: This study identified that somatic tumor mutations of STK11, KRAS, CTNNB1, KEAP1, CDKN2B, and MET were associated with an increased risk of VTE in patients with solid tumors, highlighting the need for further validation and exploration of unique molecular signatures specific to individual tumor types.
Review
Oncology
Anisha Luthra, Brooke Mastrogiacomo, Shaleigh A. Smith, Debyani Chakravarty, Nikolaus Schultz, Francisco Sanchez-Vega
Summary: NGS technologies have been widely adopted in cancer research and clinical care in the past decade, enabling patient stratification, biomarker identification, heritable cancer risk assessment, and treatment monitoring. The development of novel algorithms, computational pipelines, and structured knowledge bases has been crucial for downstream data processing and interpretation. Collaborations across institutions have led to the creation of large pooled datasets that offer valuable insights into the genomics of rare cancers.
GENES CHROMOSOMES & CANCER
(2022)
Article
Biochemistry & Molecular Biology
Kinneret Shefer, Ayub Boulos, Valer Gotea, Maram Arafat, Yair Ben Chaim, Aya Muharram, Sara Isaac, Amir Eden, Joseph Sperling, Laura Elnitski, Ruth Sperling
Summary: This study reveals that latent splice sites are highly abundant in human introns, and their activation under stress and in cancer leads to the generation of numerous nonsense mRNAs. The previously proposed mechanism to suppress latent splicing was shown to be independent of protein translation and dependent on initiator-tRNA. The nuclear protein nucleolin (NCL) was identified as directly and specifically interacting with initiator-tRNA in the nucleus, and its association with pre-mRNA was also demonstrated. It was further revealed that nucleolin is essential for the recovery of suppression of latent splicing by initiator-tRNA. Knockdown of nucleolin led to the activation of latent splicing in coding transcripts with important cellular functions. Therefore, nucleolin, as a component of the endogenous spliceosome, is proposed as the first protein of a nuclear quality control mechanism that regulates splice site selection to prevent defective mRNA generation.
Article
Biochemical Research Methods
David O. Holland, Valer Gotea, Kevin Fedkenheuer, Sushil K. Jaiswal, Catherine Baugher, Hua Tan, Michael Fedkenheuer, Laura Elnitski
Summary: Mutations in the human kinome have a causal role in cancer, affecting cell processes such as growth, proliferation, differentiation, and apoptosis. This study compares gene expression and isoform ratios between metastatic melanoma and primary tumor cells, revealing significant differences in both. The findings show that different mutational subtypes respond differently to treatments, suggesting new driver events in cancer and highlighting the importance of therapeutic target identification.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Benjamin A. Nacev, Francisco Sanchez-Vega, Shaleigh A. Smith, Cristina R. Antonescu, Evan Rosenbaum, Hongyu Shi, Cerise Tang, Nicholas D. Socci, Satshil Rana, Rodrigo Gularte-Merida, Ahmet Zehir, Mrinal M. Gounder, Timothy G. Bowler, Anisha Luthra, Bhumika Jadeja, Azusa Okada, Jonathan A. Strong, Jake Stoller, Jason E. Chan, Ping Chi, Sandra P. D'Angelo, Mark A. Dickson, Ciara M. Kelly, Mary Louise Keohan, Sujana Movva, Katherine Thornton, Paul A. Meyers, Leonard H. Wexler, Emily K. Slotkin, Julia L. Glade Bender, Neerav N. Shukla, Martee L. Hensley, John H. Healey, Michael P. La Quaglia, Kaled M. Alektiar, Aimee M. Crago, Sam S. Yoon, Brian R. Untch, Sarah Chiang, Narasimhan P. Agaram, Meera R. Hameed, Michael F. Berger, David B. Solit, Nikolaus Schultz, Marc Ladanyi, Samuel Singer, William D. Tap
Summary: Sarcomas are rare tumors with diverse genetic features and clinical outcomes. This study analyzes over 2000 sarcomas across 45 subtypes and identifies distinct genomic groups that differ from histological subgroups. The complex genetic heterogeneity of sarcomas makes it challenging to identify therapeutic targets and advance patient care. The findings of this study provide valuable insights into subtype-specific genetic alterations and will contribute to the improvement of sarcoma models and further investigations of genetic factors and treatment responses.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Yuan Liu, Neel Chudgar, Brooke Mastrogiacomo, Di He, Manendra B. Lankadasari, Samhita Bapat, Gregory D. Jones, Francisco Sanchez-Vega, Kay See Tan, Nikolaus Schultz, Semanti Mukherjee, Kenneth Offit, Yongde Bao, Matthew J. Bott, Natasha Rekhtman, Prasad S. Adusumilli, Bob T. Li, Marty W. Mayo, David R. Jones
Summary: This study reveals the role of BRMS1 gene mutation in the metastasis of lung adenocarcinoma. The BRMS1v2(A273V/A273V) mutation activates c-fos-mediated gene transcriptional regulation, promoting tumor cell invasion and metastasis. This finding offers a potential therapeutic strategy for patients with lung adenocarcinoma.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Review
Oncology
Dana M. Omer, Hannah M. Thompson, Floris S. Verheij, Jonathan B. Yuval, Roni Rosen, Nathalie R. A. Beets, Anisha Luthra, Paul B. Romesser, Philip B. Paty, Julio Garcia-Aguilar, Francisco Sanchez-Vega
Summary: Radiation therapy for prostate cancer increases the risk of developing rectal cancer compared to surgery. Treating radiation-associated rectal cancer is challenging due to limited and contradictory evidence. This review discusses the unique considerations of treating rectal cancer patients after prostate radiotherapy.