Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/12496
Title: Role of p53 in the progression of gastric cancer.
Austin Authors: Busuttil, Rita A;Zapparoli, Giada V;Haupt, Sue;Fennell, Christina;Wong, Stephen Q;Pang, Jia-Min B;Takeno, Elena A;Mitchell, Catherine;Di Costanzo, Natasha;Fox, Stephen;Haupt, Ygal;Dobrovic, Alexander ;Boussioutas, Alex
Affiliation: Department of Gastroenterology, Royal Melbourne Hospital, Parkville, Victoria, Australia
Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia
Translational Genomics and Epigenomics Laboratory, Ludwig Institute for Cancer Research, Olivia Newton-John Cancer and Wellness Centre, Heidelberg, Victoria, Australia
Tumour Suppression Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia
Cancer Genetics and Genomics Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia
Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia
Department of Pathology, University of Melbourne, Parkville, Victoria, Australia
Molecular Pathology Research and Development Laboratory, Department of Pathology Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia
Issue Date: 15-Dec-2014
Publication information: Oncotarget; 5(23): 12016-26
Abstract: Intestinal metaplasia (IM) is a premalignant lesion associated with gastric cancer (GC) but is poorly described in terms of molecular changes. Here, we explored the role of TP53, a commonly mutated gene in GC, to determine if p53 protein expression and/or the presence of somatic mutations in TP53 can be used as a predictive marker for patients at risk of progressing to GC from IM. Immunohistochemistry and high resolution melting were used to determine p53 protein expression and TP53 mutation status respectively in normal gastric mucosa, IM without concurrent GC (IM-GC), IM with concurrent GC (IM+GC) and GC. This comparative study revealed an incremental increase in p53 expression levels with progression of disease from normal mucosa, via an IM intermediate to GC. TP53 mutations however, were not detected in IM but occurred frequently in GC. Further, we identified increased protein expression of Mdm2/x, both powerful regulators of p53, in 100% of the IM+GC cohort with these samples also exhibiting high levels of wild-type p53 protein. Our data suggests that TP53 mutations occur late in gastric carcinogenesis contributing to the final transition to cancer. We also demonstrated involvement of Mdmx in GC.
Gov't Doc #: 25427447
URI: http://ahro.austin.org.au/austinjspui/handle/1/12496
URL: https://pubmed.ncbi.nlm.nih.gov/25427447
Type: Journal Article
Appears in Collections:Journal articles

Show full item record

Page view(s)

8
checked on Dec 2, 2022

Google ScholarTM

Check


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.