Article
Biochemistry & Molecular Biology
Susu Zhang, Jing Wang, Qi Liu, W. Hayes McDonald, Monica L. Bomber, Hillary M. Layden, Jacob Ellis, Scott C. Borinstein, Scott W. Hiebert, Kristy R. Stengel
Summary: Transcriptional control is a dynamic process that is challenging to study using traditional genetic methods. In this study, we used a chemical-genetic approach to quickly degrade the transcriptional activator PAX3-FOXO1 and investigated its mechanism of action. Our findings revealed that PAX3-FOXO1 is involved in regulating gene expression and maintaining chromatin accessibility and enhancer architecture.
Article
Genetics & Heredity
Line J. Manceau, Julien E. Richard Albert, Pier-Luigi J. Lollini, Maxim V. C. E. Greenberg, Pascale J. Gilardi-Hebenstreit, Vanessa E. Ribes
Summary: The chimeric proteins PAX3-FOXO1 and PAX7-FOXO1, derived from chromosomal translocations, exhibit distinct genomic occupancy and transcriptional activity, leading to different pathological manifestations in alveolar rhabdomyosarcoma.
Article
Oncology
Christine M. Heske, Yueh-Yun Chi, Rajkumar Venkatramani, Minjie Li, Michael A. Arnold, Roshni Dasgupta, Susan M. Hiniker, Douglas S. Hawkins, Leo Mascarenhas
Summary: In patients with localized, FOXO1 fusion-positive RMS, clinical factors such as age at diagnosis and tumor size can impact survival outcomes, with older age and larger tumors being adverse prognostic factors for EFS. Patients with both older age and large tumor size experience significantly inferior outcomes.
Article
Biochemistry & Molecular Biology
Qiande Hu, Liang Zhu, Yuan Li, Jianjun Zhou, Jun Xu
Summary: The study revealed that PAX3-FOXO1 inhibits ACTA1 expression at transcription and protein levels through the RhoA-MKL1-SRF signaling pathway, which may contribute to the tumorigenesis and development of ARMS. Overexpression of ACTA1 in RH30 cells was shown to inhibit cell proliferation and migration in vitro and impair tumor growth in vivo compared to the control groups.
CELL AND BIOSCIENCE
(2021)
Article
Biology
Carla Regina, Ebrahem Hamed, Geoffroy Andrieux, Sina Angenendt, Michaela Schneider, Manching Ku, Marie Follo, Marco Wachtel, Eugene Ke, Ken Kikuchi, Anton G. Henssen, Beat W. Schafer, Melanie Boerries, Amy J. Wagers, Charles Keller, Simone Hettmer
Summary: The study shows that heterogeneous expression of PAX3:FOXO1 at the single cell level in rhabdomyosarcoma cells may provide a critical advantage during tumor progression.
LIFE SCIENCE ALLIANCE
(2021)
Article
Cell Biology
Shivendra Singh, Ahmed Abu-Zaid, Hongjian Jin, Jie Fang, Qiong Wu, Tingting Wang, Helin Feng, Waise Quarni, Ying Shao, Lily Maxham, Alireza Abdolvahabi, Mi-Kyung Yun, Sivaraja Vaithiyalingam, Haiyan Tan, John Bowling, Victoria Honnell, Brandon Young, Yian Guo, Richa Bajpai, Shondra M. Pruett-Miller, Gerard C. Grosveld, Mark Hatley, Beisi Xu, Yiping Fan, Gang Wu, Eleanor Y. Chen, Taosheng Chen, Peter W. Lewis, Zoran Rankovic, Yimei Li, Andrew J. Murphy, John Easton, Junmin Peng, Xiang Chen, Ruoning Wang, Stephen W. White, Andrew M. Davidoff, Jun Yang
Summary: This study identifies KDM4B as a therapeutic vulnerability for PAX3-FOXO1(+) RMS. Inhibition of KDM4B delays tumor growth and suppresses the expression of core oncogenic transcription factors, causing epigenetic alterations of PAX3-FOXO1-governed superenhancers.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Oncology
Daniela Di Carlo, Cyrus Chargari, Jean-Yves Scoazec, Sophie Cotteret, Arthur Felix, Salma Moalla, Stephane Temam, Veronique Minard-Colin
Summary: Alveolar rhabdomyosarcoma (ARMS) is commonly associated with PAX3/PAX7-FOXO1 fusion gene, but some tumors without this fusion may have new molecular alterations. A rare case of PAX3-NCOA1 ARMS in a two-year-old girl with tongue and nodal extension was treated with a combination of therapies to preserve oral function and minimize long-term effects. International collaboration is necessary to evaluate the prognostic value of this variant fusion in ARMS.
PEDIATRIC BLOOD & CANCER
(2021)
Article
Pathology
Xinyi Zhang, Shidan Wang, Erin R. Rudzinski, Saloni Agarwal, Ruichen Rong, Donald A. Barkauskas, Ovidiu Daescu, Lauren Furman Cline, Rajkumar Venkatramani, Yang Xie, Guanghua Xiao, Patrick Leavey
Summary: This study developed a computational algorithm for subtype classification and prognosis prediction of rhabdomyosarcoma (RMS) using pathology images. The algorithm achieved good performance in classification and prediction on the test dataset, providing assistance in pathology evaluation and risk stratification.
AMERICAN JOURNAL OF PATHOLOGY
(2022)
Article
Oncology
Thomas Raze, Eve Lapouble, Brigitte Lacour, Sandra Guissou, Anne-Sophie Defachelles, Nathalie Gaspar, Olivier Delattre, Gaelle Pierron, Emmanuel Desandes
Summary: This study aimed to evaluate the impact of PAX-FOXO1 gene alterations on clinical outcomes in childhood and adolescence patients with ARMS. The study found that patients with PAX3-FOXO1 positive expression were older, had higher metastasis rates, and lower 5-year survival rates. Compared to patients with PAX7-FOXO1 positive and PAX-FOXO1 negative tumors, patients with PAX3-FOXO1 positive tumors had a higher risk of death.
PEDIATRIC BLOOD & CANCER
(2023)
Article
Plant Sciences
Wei Jiang, Xiangrong Tian, Dongdong Wang, Heidi R. Bokesch, Cheryl L. Thomas, Girma M. Woldemichael, Berkley E. Gryder, Jun S. Wei, Young K. Song, Hsien-Chao Chou, Javed Khan, Barry R. O'Keefe, Kirk R. Gustafson
Summary: Chemical investigation of the marine hydroid Dentitheca habereri led to the discovery of eight new zoanthoxanthin alkaloids, which are the first to be reported from a hydroid. Some of these compounds show potential in inhibiting PAX3-FOXO1 transcriptional activity, making them potential candidates for drug development.
JOURNAL OF NATURAL PRODUCTS
(2022)
Article
Oncology
Elisa Fiorito, Patrycja Szybowska, Ellen M. Haugsten, Michal Kostas, Geir F. Oy, Antoni Wiedlocha, Sachin Singh, Sigve Nakken, Gunhild M. Maelandsmo, Jonathan A. Fletcher, Leonardo A. Meza-Zepeda, Jorgen Wesche
Summary: This study evaluated targeting strategies for the FGFR4 V550L activating mutation in rhabdomyosarcoma. The results showed that FGF401 effectively inhibited FGFR4 V550L-dependent signaling and cell proliferation. Additionally, RAS/MAPK and PI3K/AKT were identified as druggable pathways downstream of FGFR4 V550L. Furthermore, HSP90 inhibitors efficiently impeded RMS559 cell proliferation.
BRITISH JOURNAL OF CANCER
(2022)
Article
Oncology
Ryuma Tanaka, Kyohei Inoue, Yuji Yamada, Masanori Yoshida, Haruko Shima, Jumpei Ito, Hajime Okita, Tomoru Miwa, Motohiro Kato, Hiroyuki Shimada
Summary: Primary central nervous system rhabdomyosarcoma is a rare mesenchymal tumor predominantly affecting children, often with a poor prognosis. This study presents a case of primary CNS rhabdomyosarcoma with PAX3-NCOA2 fusion and a systematic meta-review to characterize this rare tumor. The findings suggest that primary CNS rhabdomyosarcoma shares similar features with non-CNS rhabdomyosarcoma and that a trimodal treatment approach with early radiation therapy may lead to improved survival outcomes.
JOURNAL OF NEURO-ONCOLOGY
(2021)
Review
Pathology
Lesi Xie, Wei Wang, Hong Zhou, Zhijiang Han, Jinghong Xu, Zhihong Xu, Jingjing Xiang
Summary: This article presents a rare case of central nervous system alveolar rhabdomyosarcoma located in the pineal gland of a 36-year-old Chinese male. It expands our knowledge of pineal gland tumors and highlights the importance of considering OLIG2-positive round-cell tumors in the differential diagnosis.
INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY
(2022)
Article
Multidisciplinary Sciences
Takuyo Kanayama, Mitsuru Miyachi, Yohei Sugimoto, Shigeki Yagyu, Ken Kikuchi, Kunihiko Tsuchiya, Tomoko Iehara, Hajime Hosoi
Summary: The study found that PAX3-FOXO1 is associated with B7-H3 in alveolar rhabdomyosarcoma, with PAX3-FOXO1 positively regulating B7-H3 expression. Both are involved in multiple pathways related to aggressiveness in ARMS, such as cell migration and myogenic differentiation.
SCIENTIFIC REPORTS
(2021)
Article
Pathology
David O. Azorsa, Peter K. Bode, Marco Wachtel, Adam Tai Chi Cheuk, Paul S. Meltzer, Christian Vokuhl, Ulrike Camenisch, Huy Leng Khov, Beata Bode, Beat W. Schaefer, Javed Khan
Summary: Monoclonal antibodies specific to the fusion oncoproteins PAX3-FOXO1 and PAX7-FOXO1 were developed for efficient subclassification of rhabdomyosarcoma. These antibodies can accurately detect fusion proteins, aiding in routine diagnostics for improved classification of tumors.
Article
Biochemistry & Molecular Biology
M. van Geldermalsen, Q. Wang, R. Nagarajah, A. D. Marshall, A. Thoeng, D. Gao, W. Ritchie, Y. Feng, C. G. Bailey, N. Deng, K. Harvey, J. M. Beith, C. I. Selinger, S. A. O'Toole, J. E. J. Rasko, J. Holst
Article
Oncology
Amy D. Marshall, Michelle van Geldermalsen, Nicholas J. Otte, Lyndal A. Anderson, Trina Lum, Melissa A. Vellozzi, Blake K. Zhang, Annora Thoeng, Qian Wang, John E. J. Rasko, Jeff Holst
INTERNATIONAL JOURNAL OF CANCER
(2016)
Letter
Oncology
Chau-To Kwok, Amy D. Marshall, John E. J. Rasko, Justin J. L. Wong
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2017)
Article
Biochemistry & Molecular Biology
A. D. Marshall, C. G. Bailey, K. Champ, M. Vellozzi, P. O'Young, C. Metierre, Y. Feng, A. Thoeng, A. M. Richards, U. Schmitz, M. Biro, R. Jayasinghe, L. Ding, L. Anderson, E. R. Mardis, J. E. J. Rasko
Article
Oncology
Amy D. Marshall, Irina Lagutina, Gerard C. Grosveld
Article
Cell Biology
Amy D. Marshall, Charles G. Bailey, John E. J. Rasko
CURRENT OPINION IN GENETICS & DEVELOPMENT
(2014)
Article
Oncology
Amy Marshall, Monica Senna Salerno, Mark Thomas, Todd Davies, Carole Berry, Kelly Dyer, Jeremy Bracegirdle, Trevor Watson, Marie Dziadek, Ravi Kambadur, Rob Bower, Mridula Sharma
EXPERIMENTAL CELL RESEARCH
(2008)
Article
Oncology
Jessamy C. Tiffen, Charles G. Bailey, Amy D. Marshall, Cynthia Metierre, Yue Feng, Qian Wang, Sarah L. Watson, Jeff Holst, John E. J. Rasko
INTERNATIONAL JOURNAL OF CANCER
(2013)
Article
Oncology
Amy D. Marshall, Fabrizio Picchione, Ramon I. Klein Geltink, Gerard C. Grosveld
Review
Cell Biology
Amy D. Marshall, Gerard C. Grosveld
Article
Biochemistry & Molecular Biology
Adel B. Alharbi, Ulf Schmitz, Amy D. Marshall, Darya Vanichkina, Rajini Nagarajah, Melissa Vellozzi, Justin J. L. Wong, Charles G. Bailey, John E. J. Rasko
Summary: CTCF acts as a master regulator of gene transcription and chromatin organisation, with haploinsufficiency linked to tumor development and hypermethylation. Reduced levels of CTCF in different tissues led to tissue-specific differences in gene expression and alternative splicing. In liver and kidney, CTCF haploinsufficiency resulted in increased intron retention, particularly affecting genes related to cytoskeletal organization, splicing, and metabolism.
Article
Biochemistry & Molecular Biology
B Langley, M Thomas, A Bishop, M Sharma, S Gilmour, R Kambadur
JOURNAL OF BIOLOGICAL CHEMISTRY
(2002)
Article
Cell Biology
D Forbes, M Jackman, A Bishop, M Thomas, R Kambadur, M Sharma
JOURNAL OF CELLULAR PHYSIOLOGY
(2006)
Review
Pharmacology & Pharmacy
A Bishop, R Kambadur, M Sharma
EXPERT OPINION ON INVESTIGATIONAL DRUGS
(2005)