The DOI matches its Crossref record; 55 of the 57 references it cites were found in a registry or an index.
Comprehensive Mapping of p53 Pathway Alterations Reveals an Apparent Role for Both SNP309 and MDM2 Amplification in Sarcomagenesis
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Abstract
Purpose: Reactivation of p53 tumor suppressor activity in diseases such as soft-tissue sarcoma is considered an attractive means of targeted therapy. By systematically assessing alterations affecting the p53 pathway, we aimed to (a) classify sarcoma subtypes, (b) define a potential role in malignancy, and (c) identify potential patient biomarkers in this heterogeneous disease. Experimental Design: We have mapped mutational events in a panel of 192 benign or malignant bone and soft-tissue sarcomas. Analyses included TP53 and CDKN2A mutational and SNP status, MDM2 and MDM4 amplification and MDM2 SNP309 status. Results: We found an inverse relationship between MDM2 amplification and TP53 mutations, with a predominantly wild-type CDKN2A background. A high rate of point mutations in TP53 was observed uniquely in leiomyosarcoma, osteosarcoma, and MFH. Both MDM2 and MDM4 were also amplified in a subtype-specific manner, which was frequently seen as a coamplification event. We have also analyzed the risk allele frequencies for MDM2 SNP309, and show that the G allele was strongly associated with both liposarcomas and MDM2 amplification. Conclusions: Our data emphasize the critical role of p53 inactivation in sarcomagenesis, whereby different pathway alterations may be related to the heterogeneity of the disease. Moreover, we observed a strong association of malignancy with TP53 mutation, or MDM2 amplification and the presence of a G allele in SNP309, especially in lipoma versus liposarcoma. We propose, therefore, that MDM2 markers along with TP53 sequencing should be considered as patient biomarkers in clinical trials of sarcomas using MDM2 antagonists. Clin Cancer Res; 17(3); 416–26. ©2010 AACR.
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“Amplification of MDM genes or altered expression of MDM proteins is a feature of many tumours3–10 (Table 1).”
From MDM2, MDMX and p53 in oncogenesis and cancer therapy (2013) · cites this paper as [8]
In the citing paper
“The MDM2 and MDMX (also known as HDMX and MDM4) proteins are deregulated in many human cancers and exert their oncogenic activity predominantly by inhibiting the p53 tumour suppressor.”
From MDM2, MDMX and p53 in oncogenesis and cancer therapy (2013) · cites this paper as [8]
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Putative Precursors of Uterine Sarcomas
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Impact of MDM2 309T>G polymorphism on sarcomagenesis.
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Hayashi, T., Horiuchi, A., Sano, K., Kanai, Y., Yaegashi, N., Aburatani, H., & Konishi, I. (2015)
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Hayashi, T., Horiuchi, A., Kanai, Y., Shiozawa, T., Zharhary, D., Yaegashi, N., Tonegawa, S., & Konishi, I. (2016)
Genomic Analysis of Sarcomagenesis
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Biological Analyses for Characterization of the Uterine Sarcoma Using Mouse Model
Hayashi, T., Ichimura, T., Kasai, M., Kanai, Y., & Ando, H. (2017) · Journal of Gynecological Research and Obstetrics · doi:10.17352/jgro.000040
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Metadata
- Authors
- Ito, M., Barys, L., O'Reilly, T., Young, S., Gorbatcheva, B., Monahan, J., Zumstein-Mecker, S., Choong, P. F., Dickinson, I., Crowe, P., Hemmings, C., Desai, J., Thomas, D. M., & Lisztwan, J.
- Affiliations
- Peter MacCallum Cancer Centre (AU)
- Authors' Affiliations: 1Novartis Institutes for Biomedical Research, Oncology Research, Basel, Switzerland; 2Peter MacCallum Cancer Centre, Melbourne, Australia; 3Novartis Institutes for Biomedical Research, Oncology Translational Medicine, Cambridge, Massachusetts; 4Wesley Research Institute, Brisbane, Australia; 5Prince of Wales Hospital, Sydney, Australia; and 6Canberra Hospital, Canberra, Australia
- Venue
- Clinical Cancer Research
- Published
- 2011-02-01
- Volume
- 17
- Issue
- 3
- Pages
- 416-426
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- OpenAlex
- W2056955003
- Cited by
- 115
- References
- 57
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 2 · 2023: 5 · 2022: 2 · 2021: 5 · 2020: 10 · 2019: 7 · 2018: 7 · 2017: 7 · 2016: 9 · 2015: 17 · 2014: 16 · 2013: 10 · 2012: 10
- FWCI
- 3.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- ANU Open Research (Australian National University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Health Sciences › Medicine › Oncology › Sarcoma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- p53 pathway, sarcomagenesis, soft tissue sarcoma, MDM2 amplification, TP53 mutation, CDKN2A, MDM2 SNP309, liposarcoma, lipoma, leiomyosarcoma, osteosarcoma, sarcoma subtypes, MDM2 inhibitors, tumor suppressor inactivation
- MeSH terms
- Bone Neoplasms, Chromosome Mapping, Gene Amplification, Humans, Mutation, Sarcoma, Soft Tissue Neoplasms, Biomarkers, Tumor, Genes, p53, Gene Dosage, Polymorphism, Single Nucleotide, Proto-Oncogene Proteins c-mdm2
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