Article
Oncology
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, Susan J. Clark
Summary: This study used methylome sequencing to investigate the DNA methylation patterns in prostate cancer patients, and identified methylation patterns associated with prostate cancer-specific mortality, as well as prognostic biomarkers. The combination of DNA methylation biomarkers and clinicopathological measures improved the prognostic models for prostate cancer mortality.
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Article
Oncology
Natascia Marino, Rana German, Ram Podicheti, Douglas B. Rusch, Pam Rockey, Jie Huang, George E. Sandusky, Constance J. Temm, Sandra Althouse, Kenneth P. Nephew, Harikrishna Nakshatri, Jun Liu, Ashley Vode, Sha Cao, Anna Maria Storniolo
Summary: This study found molecular aberrations in normal breast tissue of women at high risk for breast cancer, which may contribute to breast cancer susceptibility. This is also the first study to molecularly characterize true normal breast tissue.
CLINICAL EPIGENETICS
(2022)
Review
Oncology
Junyuan Xie, Li Gan, Bingjian Xue, Xinxing Wang, Xinhong Pei
Summary: Breast cancer remains the leading cause of cancer-related death in women worldwide. Non-coding RNAs, especially lncRNAs, have been found to play important roles in breast cancer. The study of epigenetic modifications has also contributed to the understanding of the role of ncRNAs in breast cancer.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Gulab Sher, Nadia Aziz Salman, Abdul Q. Khan, Kirti S. Prabhu, Afsheen Raza, Michal Kulinski, Said Dermime, Mohammad Haris, Kulsoom Junejo, Shahab Uddin
Summary: Epigenetic alterations play a crucial role in the pathogenesis of breast cancer, including drug resistance and stemness features. Understanding and utilizing these modifications for breast cancer management is challenging, but holds promise for providing novel diagnostic, prognostic markers, and therapeutic options.
SEMINARS IN CANCER BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Eshaan Patnaik, Chikezie Madu, Yi Lu
Summary: Epigenetics plays a crucial role in gene regulation and tumor development. DNA methylation inhibitors and histone deacetylase inhibitors can restore normal gene expression and be effective against cancer. Understanding epigenetic modifications and utilizing inhibitors offer new possibilities for cancer research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Sadaf Harandi-Zadeh, Cayla Boycott, Megan Beetch, Tony Yang, Benjamin J. E. Martin, Kevin Ren, Anna Kwasniak, John H. Dupuis, Katarzyna Lubecka, Rickey Y. Yada, LeAnn J. Howe, Barbara Stefanska
Summary: Epigenetic aberrations are associated with sporadic breast cancer, and dietary polyphenols such as pterostilbene have been shown to regulate gene expression by altering epigenetic patterns. The study reveals an impact of pterostilbene on enhancer regions in breast cancer cells, affecting DNMT3B binding, H3K36me3 levels, enhancer hypermethylation, and gene expression downregulation. Additionally, the research highlights the involvement of oncogenic transcription factor OCT1 in mediating the effects of pterostilbene on enhancers and gene expression in breast cancer cells.
Review
Biochemistry & Molecular Biology
Sarah S. Wang, Jihao Xu, Keely Y. Ji, Chang-Il Hwang
Summary: Pancreatic cancer, particularly pancreatic ductal adenocarcinoma (PDA), is a significant cause of cancer-related deaths in the United States. While genetic mutations driving PDA initiation and progression have been identified, the mechanisms underlying PDA metastasis remain elusive. It is suggested that epigenetic fluctuations may play a critical role in driving PDA metastasis.
Article
Oncology
Joana Dias Apolonio, Joao S. Dias, Monica Teotonio Fernandes, Martin Komosa, Tatiana Lipman, Cindy H. Zhang, Ricardo Leao, Donghyun Lee, Nuno Miguel Nunes, Ana-Teresa Maia, Jose L. Morera, Luis Vicioso, Uri Tabori, Pedro Castelo-Branco
Summary: THOR hypermethylation plays an important role in breast tumorigenesis and is associated with hTERT upregulation, making it a potential biomarker and therapeutic target for breast cancer.
CLINICAL EPIGENETICS
(2022)
Article
Biochemistry & Molecular Biology
Sara Monteiro-Reis, Vera Miranda-Goncalves, Catarina Guimaraes-Teixeira, Claudia Martins-Lima, Joao Lobo, Diana Montezuma, Paula C. Dias, Helene Neyret-Kahn, Isabelle Bernard-Pierrot, Rui Henrique, Carmen Jeronimo
Summary: In this study, we found that the VIM promoter is epigenetically regulated in normal and neoplastic urothelium, leading to a switch in VIM expression associated with EMT and the acquisition of invasive and metastatic properties. These findings might contribute to the development of novel therapeutic strategies for bladder cancer based on epigenetics.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Review
Oncology
Yuhao Zhao, Mao Yang, Shijia Wang, Sk Jahir Abbas, Junzhe Zhang, Yongsheng Li, Rong Shao, Yingbin Liu
Summary: This review focuses on the mechanistic insights of DNA, histone, and RNA methylation in regulating the progression of pancreatic cancer. The roles of methylation regulators in modulating gene expression associated with cell proliferation, invasion, and apoptosis are discussed. Recent clinical trials on methylation drug targeting are also explored. Understanding the novel regulatory mechanisms of methylation modification may offer alternative opportunities to improve therapeutic efficacy in combating this devastating disease.
FRONTIERS IN ONCOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Lirui Wang, Chunlei Zhang, Yuping Hong, Xinhong Li, Tangan Li, Ang Gao, Shaojun Pan, Bin Liu, Han Jin, Daxiang Cui
Summary: The study developed a method of combinatorial delivery of epigenetic modulatory drugs through self-assembly, effectively regulating DNA methylation and histone deacetylation, ultimately inhibiting tumor cell proliferation and promoting cell apoptosis.
Article
Oncology
Jamaji C. Nwanaji-Enwerem, Felicia Fei-Lei Chung, Lars Van der Laan, Alexei Novoloaca, Cyrille Cuenin, Harriet Johansson, Bernardo Bonanni, Alan E. Hubbard, Martyn T. Smith, Sheri J. Hartman, Andres Cardenas, Dorothy D. Sears, Zdenko Herceg
Summary: The study conducted a 6-month trial on breast cancer survivors and found limited effect of metformin on decelerating epigenetic age. Although there was a high correlation with chronological age, no significant association was observed between intervention arms and epigenetic age. Longer duration studies are needed to further characterize these relationships.
CLINICAL EPIGENETICS
(2021)
Review
Oncology
Vasiliki Zolota, Vasiliki Tzelepi, Zoi Piperigkou, Helen Kourea, Efthymia Papakonstantinou, Maria-Ioanna Argentou, Nikos K. Karamanos
Summary: Current data suggest that epigenetic alterations play a key role in the initiation and subclonal evolution of breast cancer, especially in the aggressive molecular subgroup of triple-negative breast cancer. The extracellular matrix undergoes significant structural alterations during cancer progression, which are closely linked with epigenetic modifiers. Targeting tumor microenvironment and epigenetic pathways may provide potential therapeutic strategies, particularly in triple-negative breast cancer where standard chemotherapy is limited.
Article
Biochemistry & Molecular Biology
Dong Zhang, Yingnan Wang, Qifeng Yang
Summary: The study identified and validated a 10-CpG-based prognostic signature in breast cancer patients, showing correlation with immune characteristics. High-risk patients exhibited upregulated immune-inhibited oncogenic pathways, higher TP53 mutations, and lower responsiveness to treatments.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Review
Biotechnology & Applied Microbiology
Deepa Ramasamy, Arunagiri Kuha Deva Magendhra Rao, Thangarajan Rajkumar, Samson Mani
Summary: Non-CpG methylation, a distinct epigenetic modification in DNA, plays a crucial role in gene regulation. Advances in technology have allowed for a better understanding of its genome-wide distribution, but its specific role in cancer development remains unclear. This review focuses on the mechanism of non-CpG methylation in embryos and tissues, particularly its relevance to cancer progression.
BRIEFINGS IN FUNCTIONAL GENOMICS
(2021)
Article
Oncology
Jiehui Deng, Aatish Thennavan, Suhagi Shah, Ece Bagdatlioglu, Natalie Klar, Adriana Heguy, Christian Marier, Peter Meyn, Yutong Zhang, Kristen Labbe, Christina Almonte, Michelle Krogsgaard, Charles M. Perou, Kwok-Kin Wong, Sylvia Adams
Summary: This study utilized single-cell RNA sequencing to analyze immune cell changes in two advanced TNBC patients undergoing different treatment stages, revealing heterogeneity in tumor-infiltrating immune cell populations and modulation of the tumor microenvironment by chemotherapy and immunotherapy. Notably, a responding patient showed a decrease in PD-1(high)-expressing T cells after chemo-immunotherapy, while a progressor demonstrated a prevalent and persistent myeloid compartment in the tumors.
BREAST CANCER RESEARCH AND TREATMENT
(2021)
Article
Medicine, General & Internal
Nuria Chic, Francesco Schettini, Fara Braso-Maristany, Esther Sanfeliu, Barbara Adamo, Maria Vidal, Debora Martinez, Patricia Galvan, Blanca Gonzalez-Farre, Javier Cortes, Joaquin Gavila, Cristina Saura, Mafalda Oliveira, Sonia Pernas, Olga Martinez-Saez, Jesus Soberino, Eva Ciruelos, Lisa A. Carey, Montserrat Munoz, Charles M. Perou, Tomas Pascual, Meritxell Bellet, Aleix Prat
Summary: Chemotherapy has different biological effects on patients with hormone receptor-positive breast cancer with different menopausal statuses. Specific estrogen-regulated genes exhibited varied expression levels under different treatment regimens in these patients.
Article
Oncology
Amber N. Hurson, Mustapha Abubakar, Alina M. Hamilton, Kathleen Conway, Katherine A. Hoadley, Michael Love, Andrew F. Olshan, Charles M. Perou, Montserrat Garcia-Closas, Melissa A. Troester
Summary: This study identified breast cancer risk factors associated with RNA-based TP53 and ER, providing a new etiologic schema of interest in breast cancer prevention research.
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2022)
Article
Oncology
Achal Patel, Montserrat Garcia-Closas, Andrew F. Olshan, Charles M. Perou, Melissa A. Troester, Michael Love, Arjun Bhattacharya
Summary: This study identifies race-specific genetic associations with breast cancer risk of recurrence scores and suggests mediation of these associations by PAM50 subtype and expression, with implications for clinical interpretation of these scores.
Article
Oncology
Carey K. Anders, Mark G. Woodcock, Amanda E. D. Van Swearingen, Dominic T. Moore, Maria J. Sambade, Sonia Laurie, Alexander Robeson, Oleg Kolupaev, Luz A. Cuaboy, Amy L. Garrett, Karen McKinnon, Kristen Cowens, Dante Bortone, Benjamin C. Calhoun, Alec D. Wilkinson, Lisa Carey, Trevor Jolly, Hyman Muss, Katherine Reeder-Hayes, Rebecca Kaltman, Rachel Jankowitz, Vinay Gudena, Oludamilola Olajide, Charles Perou, E. Claire Dees, Benjamin G. Vincent, Jonathan S. Serody
Summary: This study evaluated the efficacy of using a low dose of cyclophosphamide (Cy) to deplete regulatory T cells (T-regs) before initiating pembrolizumab in patients with triple negative breast cancer (TNBC). The results showed that Cy did not significantly decrease T-regs before pembrolizumab and there was a rapid recovery in T-regs after the first cycle of therapy. Baseline samples with increased B cell gene expression were associated with clinical response and immune-related toxicity (IRT).
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Alina M. Hamilton, Amber N. Hurson, Linnea T. Olsson, Andrea Walens, Joseph Nsonwu-Farley, Erin L. Kirk, Yara Abdou, Stephanie M. Downs-Canner, Jonathan S. Serody, Charles M. Perou, Benjamin C. Calhoun, Melissa A. Troester, Katherine A. Hoadley
Summary: The immune microenvironment in breast cancer is closely related to race, age, tumor subtype, and grade. Black and young women have higher immune response, which may be associated with higher recurrence risk.
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2022)
Article
Oncology
Sonam Bhatia, Melissa Kramer, Suzanne Russo, Payal Naik, Gayatri Arun, Kyle Brophy, Peter Andrews, Cheng Fan, Charles M. Perou, Jonathan Preall, Taehoon Ha, Dennis Plenker, David A. Tuveson, Arvind Rishi, John E. Wilkinson, W. Richard McCombie, Karen Kostroff, David L. Spector
Summary: This study developed a diverse biobank of patient-derived organoids of triple-negative breast cancer (TNBC) and provided comprehensive insights into TNBC biology and progression. The organoids successfully recapitulated patient tumor characteristics and identified potential mechanisms of tumorigenesis at the single-cell level.
Editorial Material
Oncology
Sarah Asad, Kathryn Kananen, Kurt R. Mueller, W. Fraser Symmans, Yujia Wen, Charles M. Perou, James S. Blachly, James Chen, Benjamin G. Vincent, Daniel G. Stover
JCO CLINICAL CANCER INFORMATICS
(2022)
Article
Biochemistry & Molecular Biology
Ryan L. Collins, Joseph T. Glessner, Eleonora Porcu, Maarja Lepamets, Rhonda Brandon, Christopher Lauricella, Lide Han, Theodore Morley, Lisa-Marie Niestroj, Jacob Ulirsch, Selin Everett, Daniel P. Howrigan, Philip M. Boone, Jack Fu, Konrad J. Karczewski, Georgios Kellaris, Chelsea Lowther, Diane Lucente, Kiana Mohajeri, Margit Noukas, Xander Nuttle, Kaitlin E. Samocha, Mi Trinh, Farid Ullah, Urmo Vosa, Matthew E. Hurles, Swaroop Aradhya, Erica E. Davis, Hilary Finucane, James F. Gusella, Aura Janze, Nicholas Katsanis, Ludmila Matyakhina, Benjamin M. Neale, David Sanders, Stephanie Warren, Jennelle C. Hodge, Dennis Lal, Douglas M. Ruderfer, Jeanne Meck, Reedik Magi, Tonu Esko, Alexandre Reymond, Zoltan Kutalik, Hakon Hakonarson, Shamil Sunyaev, Harrison Brand, Michael E. Talkowski
Summary: This study aims to quantify the properties of haploinsufficiency and triplosensitivity throughout the human genome and construct a genome-wide catalog of dosage sensitivity for 54 disorders. The study identified dosage sensitive segments and developed a machine-learning model to predict probabilities of dosage sensitivity for all autosomal genes.
Article
Oncology
Youli Xia, Xiaping He, Lorna Renshaw, Carlos Martinez-Perez, Charlene Kay, Mark Gray, James Meehan, Joel S. Parker, Charles M. Perou, Lisa A. Carey, J. Michael Dixon, Arran Turnbull
Summary: This study identified molecular mechanisms underlying endocrine therapy resistance (ETR) in hormone receptor-positive breast cancer through in-depth genomic analysis. The results showed that ETR involves diverse changes in somatic genetic and transcriptomic profiles, including mutations, gene expression changes, and activation of signaling pathways. Overcoming resistance will require an individualized approach utilizing genomic and genetic biomarkers and drugs tailored to each patient.
CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Audrey Y. Jung, Thomas U. Ahearn, Sabine Behrens, Pooja Middha, Manjeet K. Bolla, Qin Wang, Volker Arndt, Kristan J. Aronson, Annelie Augustinsson, Laura E. Beane Freeman, Heiko Becher, Hermann Brenner, Federico Canzian, Lisa A. Carey, Cts Consortium, Kamila Czene, A. Heather Eliassen, Mikael Eriksson, D. Gareth Evans, Jonine D. Figueroa, Lin Fritschi, Marike Gabrielson, Graham G. Giles, Pascal Guenel, Andreas Hadjisavvas, Christopher A. Haiman, Niclas Hakansson, Per Hall, Ute Hamann, Reiner Hoppe, John L. Hopper, Anthony Howell, David J. Hunter, Anika Huesing, Rudolf Kaaks, Veli-Matti Kosma, Stella Koutros, Peter Kraft, James Lacey, Loic Le Marchand, Jolanta Lissowska, Maria A. Loizidou, Arto Mannermaa, Tabea Maurer, Rachel A. Murphy, Andrew F. Olshan, Hakan Olsson, Alpa Patel, Charles M. Perou, Gad Rennert, Rana Shibli, Xiao-Ou Shu, Melissa C. Southey, Jennifer Stone, Rulla M. Tamimi, Lauren R. Teras, Melissa A. Troester, Therese Truong, Celine M. Vachon, Sophia S. Wang, Alicja Wolk, Anna H. Wu, Xiaohong R. Yang, Wei Zheng, Alison M. Dunning, Paul D. P. Pharoah, Douglas F. Easton, Roger L. Milne, Nilanjan Chatterjee, Marjanka K. Schmidt, Montserrat Garcia-Closas, Jenny Chang-Claude
Summary: Reproductive factors are differentially associated with risk of breast cancer subtypes, and triple-negative breast cancer has a distinct reproductive risk factor profile.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2022)
Article
Oncology
Aatish Thennavan, Susana Garcia-Recio, Siyao Liu, Xiaping He, Charles M. Perou
Summary: Ductal carcinoma in situ (DCIS) of the breast is a precursor of invasive ductal carcinoma (IDC). This study utilizes mouse models and human samples to identify features associated with DCIS progression. The analysis reveals malignant cells and tumor microenvironmental changes in DCIS and IDC, and suggests the existence of intrinsic subtype unique DCIS features. The findings may contribute to the identification and treatment of progression-prone DCIS in human basal-like breast cancers.
Article
Multidisciplinary Sciences
Petko P. Fiziev, Jeremy McRae, Jacob C. Ulirsch, Jacqueline S. Dron, Tobias Hamp, Yanshen Yang, Pierrick Wainschtein, Zijian Ni, Joshua G. Schraiber, Hong Gao, Dylan Cable, Yair Field, Francois Aguet, Marc Fasnacht, Ahmed Metwally, Jeffrey Rogers, Tomas Marques-Bonet, Heidi L. Rehm, Anne O'Donnell-Luria, Amit Khera, Kyle Kai-How Farh
Summary: We discovered that rare, penetrant mutations in genes associated with complex traits and common diseases have about 10-fold larger effects than common variants in the same genes. By identifying individuals at the phenotypic extreme and at risk for severe, early-onset disease through rare penetrant variants, rather than relying on many weak common variants, we greatly improve the clinical utility of genetic-based risk prediction. Our unified genetic risk model, combining rare variants across phenotype-associated genes, shows superior portability across diverse global populations compared to common-variant polygenic risk scores.
Article
Oncology
Frederick M. Howard, James Dolezal, Sara Kochanny, Galina Khramtsova, Jasmine Vickery, Andrew Srisuwananukorn, Anna Woodard, Nan Chen, Rita Nanda, Charles M. Perou, Olufunmilayo I. Olopade, Dezheng Huo, Alexander T. Pearson
Summary: Gene expression-based recurrence assays are recommended for guiding chemotherapy in hormone receptor-positive, HER2-negative breast cancer, but their high cost and limited availability pose challenges. This study presents a deep learning model that utilizes digital histology and clinical risk factors to predict recurrence assay results and the risk of recurrence, surpassing the performance of established clinical nomograms. The model can identify patients with excellent prognoses who may not require further genomic testing.
Article
Genetics & Heredity
Elle M. M. Weeks, Jacob C. C. Ulirsch, Nathan Y. Y. Cheng, Brian L. L. Trippe, Rebecca S. S. Fine, Jenkai Miao, Tejal A. A. Patwardhan, Masahiro Kanai, Joseph Nasser, Charles P. P. Fulco, Katherine C. C. Tashman, Francois Aguet, Taibo Li, Jose Ordovas-Montanes, Christopher S. S. Smillie, Moshe Biton, Alex K. K. Shalek, Ashwin N. N. Ananthakrishnan, Ramnik J. J. Xavier, Aviv Regev, Rajat M. M. Gupta, Kasper Lage, Kristin G. G. Ardlie, Joel N. N. Hirschhorn, Eric S. S. Lander, Jesse M. M. Engreitz, Hilary K. K. Finucane
Summary: Polygenic Priority Score (PoPS) integrates genome-wide association summary statistics with other data types to prioritize candidate effector genes at complex trait loci. Combining PoPS with methods that leverage local genetic signals improves performance. In this study, PoPS is introduced as a new method to prioritize genes at GWAS loci by learning trait-relevant gene features. By combining PoPS with orthogonal methods, 10,642 unique gene-trait pairs across 113 complex traits and diseases are prioritized with high precision, including both well-established gene-trait relationships and new genes at unresolved loci.