Article
Biochemistry & Molecular Biology
Byungkyu Park, Jinho Im, Kyungsook Han
Summary: Breast cancer is a common and deadly cancer among females. Basal-like breast cancer, one of its subtypes, has the lowest survival rate with no effective treatments available. This study aimed to identify gene correlations and potential prognostic gene pairs for breast cancer patients. Comparative analysis revealed several new gene pairs with opposing correlations and prognostic genes for patients with a wild-type TP53 gene. Findings from this study provide important insights for prognosis and drug target selection in breast cancer, especially in basal-like breast cancer.
Article
Hematology
Mehrnoosh Tashakori, Tapan Kadia, Sanam Loghavi, Naval Daver, Rashmi Kanagal-Shamanna, Sherry Pierce, Dawen Sui, Peng Wei, Farnoosh Khodakarami, Zhenya Tang, Mark Routbort, Carol A. Bivins, Elias J. Jabbour, L. Jeffrey Medeiros, Kapil Bhalla, Hagop M. Kantarjian, Farhad Ravandi, Joseph D. Khoury
Summary: Mutant TP53 is a risk factor in AML, but there is limited analysis of TP53 alterations in AML patients. Our study analyzed TP53 mutational status, copy number, and protein expression in AML patients and identified different hotspots and novel pathogenic variants involving TP53 splice sites. We found TP53 CN loss in TP53-mutated AML cases and copy neutral loss of heterozygosity in AML patients with intact TP53 CN. We also demonstrated that mutant p53 protein expression patterns can provide a readout that integrates TP53 mutation and allelic states in AML patients, regardless of TP53 CN status. Additionally, genomic analysis of comutations in TP53-mutant AML showed mutations in genes involved in epigenetic regulation, RAS/MAPK signaling, and RNA splicing. This study provides insights for risk stratification of AML patients based on integrated molecular and protein-level TP53 analyses.
Article
Oncology
Karim H. Saba, Valeria Difilippo, Michal Kovac, Louise Cornmark, Linda Magnusson, Jenny Nilsson, Hilda van den Bos, Diana C. J. Spierings, Mahtab Bidgoli, Tord Jonson, Vaiyapuri P. Sumathi, Otte Brosjoe, Johan Staaf, Floris Foijer, Emelie Styring, Michaela Nathrath, Daniel Baumhoer, Karolin H. Nord
Summary: TP53 is a frequently mutated gene in human cancer. In the study of osteosarcoma, a primary bone malignancy, it was found that TP53 structural variants commonly result in loss of coding parts of the gene while simultaneously preserving and relocating the promoter region. The transferred TP53 promoter region is fused to genes previously implicated in cancer development, and paradoxically, these upregulated genes are significantly associated with the TP53 signalling pathway itself.
JOURNAL OF PATHOLOGY
(2023)
Article
Oncology
Dongmei Chen, Chenyang Zhang, Mengqi Yuan, Ying Zhang, Qing Liu, Donggui Wan
Summary: This article reports a case of a 14-year-old female with triple-negative breast cancer and a family history of malignant tumors. The case highlights the importance of genetic testing in early onset breast cancer to confirm inherited risk and recommends genetic testing for relatives.
FRONTIERS IN ONCOLOGY
(2022)
Article
Medicine, Research & Experimental
Xin Chen, Tianqi Liu, Jianqi Wu, Chen Zhu, Gefei Guan, Cunyi Zou, Qing Guo, Xiaolin Ren, Chen Li, Peng Cheng, Wen Cheng, Anhua Wu
Summary: This study extracted genetic and epigenetic features of TP53mut tumors and identified five different subtypes of TP53mut patients. These subtypes have distinct characteristics in terms of genomic alterations, clinical relevance, microenvironment dysregulation, and potential therapeutics. Among the subtypes, COCA3 was identified as having the worst prognosis, while olaparib showed promising therapeutic efficacy.
Article
Cell Biology
Ziwen Zhang, Ran Hao, Qiusheng Guo, Sheyu Zhang, Xiaojia Wang
Summary: The TP53 mutation is significantly associated with a shorter overall survival in patients with breast cancer, and is an independent predictive factor for overall survival. The TP53-mutant group exhibits higher tumor mutation burden, microsatellite instability, and tumor immune dysfunction and exclusion values for immunotherapy. In addition, TP53 mutation is related to increased ImmuneScore and StromalScore, and promotes the infiltration of Tregs, T helper cells, and M0-type macrophages in the tumor microenvironment.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Obstetrics & Gynecology
Sabine Grill, Juliane Ramser, Heide Hellebrand, Nicole Pfarr, Melanie Boxberg, Christine Brambs, Nina Ditsch, Alfons Meindl, Eva Gross, Thomas Meitinger, Marion Kiechle, Anne S. Quante
Summary: TP53germline mutations are rarely reported in the context of hereditary breast and ovarian cancer (HBOC). Through next-generation sequencing on 1876 breast cancer patients, it was found that (likely) pathogenic variants in the TP53 gene were present in 0.6% of the cohort, with higher occurrence in early-onset breast cancer and bilateral cases. Among the HBOC families, a clinical subgroup distinct from classic LFS families was identified, leading to potential for individualized screening efforts.
ARCHIVES OF GYNECOLOGY AND OBSTETRICS
(2021)
Article
Biotechnology & Applied Microbiology
Xiulei Zhang, Zhihao Fu, Xiao Zhang
Summary: This study investigates the landscape of genomic alterations and lncRNA prognosis markers related to TP53 mutation in Hepatocellular carcinoma (HCC). TP53 mutation is associated with poor clinical outcomes in Stage II and Stage III HCC patients, affecting pathways like DNA replication, cell cycle, and immune response. Two lncRNAs (RP4-736L20.3 and SNRK-AS1) are identified as significant prognosis markers for HCC patients with TP53 mutation.
ONCOTARGETS AND THERAPY
(2021)
Article
Cell Biology
Asmaa Y. Abuhamad, Nurul Nadia Mohamad Zamberi, Ling Sheen, Safaa M. Naes, Siti Nur Hasanah Mohd Yusuf, Asilah Ahmad Tajudin, M. Aiman Mohtar, Amir Syahir Amir Hamzah, Saiful Effendi Syafruddin
Summary: Breast cancer is often caused by genetic alterations, particularly missense mutations, in the TP53 gene. This study used CRISPR-based gene editing technology, specifically the prime editing tool, to revert and introduce a specific TP53 mutation in breast cancer cell lines. Sanger sequencing was initially used but proved to be less sensitive than amplicon target sequencing, which detected the expected substitutions. The overall editing efficiency was low, suggesting the need for workflow and efficiency improvements in future experiments.
Article
Radiology, Nuclear Medicine & Medical Imaging
Yunxia Huang, Yu Qiang, Le Jian, Zhou Jin, Qian Lang, Chen Sheng, Zhou Shichong, Chang Cai
Summary: This study aimed to predict mutations in TP53 and PIK3CA genes in breast cancer using ultrasound signatures and clinicopathology. The models combining ultrasound features and molecular subtypes have implications for predicting gene mutations and individual treatment planning.
ACADEMIC RADIOLOGY
(2022)
Article
Physics, Fluids & Plasmas
Moupriya Das, Holger Kantz
Summary: During processes like transcription, translation, or self-replication of DNA or RNA, information is transferred from predecessor to newly formed species. The accuracy of copying processes is essential, and there exists an optimum temperature range where mutation is most unlikely.
Article
Oncology
Binliang Liu, Zongbi Yi, Yanfang Guan, Quchang Ouyang, Chunxiao Li, Xiuwen Guan, Dan Lv, Lixi Li, Jingtong Zhai, Haili Qian, Binghe Xu, Fei Ma, Yixin Zeng
Summary: This study used targeted capture sequencing to analyze TP53-mutated ctDNA in metastatic breast cancer patients. It found that TP53 mutation can be used to predict the efficacy of anti-HER2 antibody treatment and has different prognostic implications in HER2+ and HER2-/mut patients.
Article
Oncology
Ji-Yeon Kim, Jaeyun Jung, Kyoung-Mee Kim, Jeeyun Lee, Young-Hyuck Im
Summary: This study aimed to explain the reason why the R175H mutation worsens the response to immunotherapy by analyzing the tumor immune microenvironment through the expression of immune cells and PD-1. The results showed that patients with TP53 R175H mutations had significantly worse overall survival following chemotherapy or immunotherapy compared to those with TP53 mutations in other loci.
Review
Oncology
Thierry Soussi
Summary: With the advancement of genotyping technology, a large number of uncommon SNPs have been discovered, but many resources are biased towards European populations. TP53 gene is the most frequently mutated gene in human cancer, and its SNPs must be rigorously evaluated to avoid misclassifications. The recent discovery of numerous benign SNPs within the coding region of TP53 highlights the importance of including populations of different ethnic origins in genetic studies.
Article
Oncology
Emilia Ip, Alison Luk Young, Tahlia Scheinberg, Michelle Harrison, Philip Beale, Annabel Goodwin
Summary: This study retrospectively reviewed a mainstream genetic testing program for ovarian cancer in Sydney. The results showed a successful uptake of the program by medical oncologists, with an increasing proportion of eligible patients accessing genetic testing over time. Pathogenic variants were detected in a significant number of patients through mainstream testing, leading to appropriate posttest counseling.
ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY
(2022)
Meeting Abstract
Hematology
Pragya Srivastava, Stephanie Tzetzo, Eduardo Cortes Gomez, Kevin Eng, Prashant K. Singh, Kitty De Jong, Sheila N. J. Sait, Kyle Wiatrowski, Miranda L. Lynch, Jennifer Peresie, Jianmin Wang, Elizabeth A. Griffiths, Michael J. Nemeth
Article
Oncology
Devalingam Mahalingam, Grey A. Wilkinson, Kevin H. Eng, Paul Fields, Patrick Raber, Jennifer L. Moseley, Karol Cheetham, Matt Coffey, Gerard Nuovo, Pawel Kalinski, Bin Zhang, Sukeshi Patel Arora, Christos Fountzilas
CLINICAL CANCER RESEARCH
(2020)
Article
Biochemistry & Molecular Biology
Swati Venkat, Arwen A. Tisdale, Johann R. Schwarz, Abdulrahman Alahmari, H. Carlo Maurer, Kenneth Olive, Kevin H. Eng, Michael E. Feigin
Article
Oncology
Anm Nazmul H. Khan, Tiffany R. Emmons, Jerry T. Wong, Emad Alqassim, Kelly L. Singel, Jaron Mark, Brandon E. Smith, Joseph D. Tario, Kevin H. Eng, Kirsten B. Moysich, Kunle Odunsi, Scott I. Abrams, Brahm H. Segal
CANCER IMMUNOLOGY RESEARCH
(2020)
Meeting Abstract
Oncology
S. Lynam, F. O. Recio, M. Roy, S. Belliotti, S. N. Akers, P. J. Frederick, S. B. Lele, E. Zsiros, K. H. Eng, K. Odunsi
GYNECOLOGIC ONCOLOGY
(2020)
Article
Oncology
Ashley Mussell, He Shen, Yanmin Chen, Michalis Mastri, Kevin H. Eng, Wiam Bshara, Costa Frangou, Jianmin Zhang
Article
Biology
Justin Zonneville, Moyi Wang, Mohammed M. Alruwaili, Brandon Smith, Megan Melnick, Kevin H. Eng, Thomas Melendy, Ben Ho Park, Renuka Iyer, Christos Fountzilas, Andrei Bakin
Summary: Zonneville et al. demonstrate that p53 mutant cancers with high replication activity and BER pathway expression can be targeted using a combination of fluorinated deoxyuridine analogues and PARP inhibitors, resulting in DNA damage induction and tumor growth suppression in mice. This study highlights a novel selective combination therapy strategy for p53 mutant cancers that shows a greater anti-neoplastic efficacy compared to monotherapy.
COMMUNICATIONS BIOLOGY
(2021)
Article
Oncology
James Ellegate, Michalis Mastri, Emily Isenhart, John J. Krolewski, Gurkamal Chatta, Eric Kauffman, Melissa Moffitt, Kevin H. Eng
Summary: The MAGEC3 gene is found to be lost in ovarian cancers, and its loss is associated with better survival rate. The MAGEC3 protein is also correlated with immune-related features and DNA repair pathway expression. Therefore, MAGEC3 is considered a prognostic biomarker in ovarian cancer.
Article
Oncology
Chetan C. Oturkar, Nishant Gandhi, Pramod Rao, Kevin H. Eng, Austin Miller, Prashant K. Singh, Emese Zsiros, Kunle O. Odunsi, Gokul M. Das
Summary: High grade serous ovarian cancer (HGSOC) is a common and deadly subtype of ovarian cancer with a high prevalence of mutant p53. This study investigated the interaction between estrogen receptor-beta (ER beta) and mutant p53 in HGSOC. The researchers found that ER beta 2 and mutant p53 co-dependently regulated the transcription of the FOXM1 gene, leading to increased cell proliferation and resistance to treatment. High levels of ER beta 2 and FOXM1 were correlated with worse patient survival. This suggests that targeting the ER beta 2-mutant p53-FOXM1 axis could be a novel therapeutic strategy for HGSOC.
Article
Oncology
Emmanuel B. Omole, Iqbal Aijaz, James Ellegate, Emily Isenhart, Mohamed M. Desouki, Michalis Mastri, Kristen Humphrey, Emily M. Dougherty, Spencer R. Rosario, Kent L. Nastiuk, Joyce E. Ohm, Kevin H. Eng
Summary: The study revealed a weak inverse correlation between the expression of MAGEC3 and BRCA2 in epithelial ovarian cancer, suggesting that the combined expression of MAGEC3 and BRCA2 may serve as a better predictor of prognosis than each marker alone.
Meeting Abstract
Immunology
Sora Suzuki, Thejaswini Giridharan, A. N. M. Nazmul Khan, Tiffany R. Emmons, Michael B. Yaffe, Kipp Weiskopf, Madhumita Das, Kevin H. Eng, Emese Zsiros, Brahm H. Segal
JOURNAL OF IMMUNOLOGY
(2022)
Meeting Abstract
Oncology
Justin Zonneville, Moyi Wang, Mohammed Alruwaili, Kevin Eng, Thomas Melendy, Ben Ho Park, Renuka Iyer, Christos Fountzilas, Andrei V. Bakin
Meeting Abstract
Oncology
Yuhao Shi, Melissa Dolan, Michalis Mastri, James W. Hill, Kevin Eng, John M. Ebos
Article
Medicine, Research & Experimental
Chunliu Pan, Neha Jaiswal Agrawal, Yanni Zulia, Shalini Singh, Kai Sha, James L. Mohler, Kevin H. Eng, Joe Chakkalakal, John J. Krolewski, Kent L. Nastiuk
Meeting Abstract
Oncology
H. Takahashi, W. He, L. Spokauskaite, K. H. Eng, A. Witkiewicz, F. Ito
ANNALS OF SURGICAL ONCOLOGY
(2019)
