Breast Cancer Patient Prognosis Is Determined by the Interplay between TP53 Mutation and Alternative Transcript Expression: Insights from TP53 Long Amplicon Digital PCR Assays

Simple item page
dc.citation.issue7
dc.citation.volume13
dc.contributor.authorLasham A
dc.contributor.authorKnowlton N
dc.contributor.authorMehta SY
dc.contributor.authorBraithwaite AW
dc.contributor.authorPrint CG
dc.coverage.spatialSwitzerland
dc.date.accessioned2025-03-19T00:15:49Z
dc.date.available2025-03-19T00:15:49Z
dc.date.issued2021-03-26
dc.description.abstractThe TP53 gene locus is capable of producing multiple RNA transcripts encoding the different p53 protein isoforms. We recently described multiplex long amplicon droplet digital PCR (ddPCR) assays to quantify seven of eight TP53 reference transcripts in human tumors. Here, we describe a new long amplicon ddPCR assay to quantify expression of the eighth TP53 reference transcript encoding ∆40p53α. We then applied these assays, alongside DNA sequencing of the TP53 gene locus, to tumors from a cohort of New Zealand (NZ) breast cancer patients. We found a high prevalence of mutations at TP53 splice sites in the NZ breast cancer cohort. Mutations at TP53 intron 4 splice sites were associated with overexpression of ∆133TP53 transcripts. Cox proportional hazards survival analysis showed that interplay between TP53 mutation status and expression of TP53 transcript variants was significantly associated with patient outcome, over and above standard clinical and pathological information. In particular, patients with no TP53 mutation and a low ratio of TP53 transcripts t2 to t1, which derive from alternative intron 1 acceptor splice sites, had a remarkably good outcome. We suggest that this type of analysis, integrating mutation and transcript expression, provides a step-change in our understanding of TP53 in cancer.
dc.description.confidentialfalse
dc.edition.editionApril 2021
dc.format.pagination1531-
dc.identifier.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/33810361
dc.identifier.citationLasham A, Knowlton N, Mehta SY, Braithwaite AW, Print CG. (2021). Breast Cancer Patient Prognosis Is Determined by the Interplay between TP53 Mutation and Alternative Transcript Expression: Insights from TP53 Long Amplicon Digital PCR Assays.. Cancers (Basel). 13. 7. (pp. 1531-).
dc.identifier.doi10.3390/cancers13071531
dc.identifier.eissn2072-6694
dc.identifier.elements-typejournal-article
dc.identifier.issn2072-6694
dc.identifier.number1531
dc.identifier.piicancers13071531
dc.identifier.urihttps://mro.massey.ac.nz/handle/10179/72672
dc.languageeng
dc.publisherMDPI (Basel, Switzerland)
dc.publisher.urihttps://www.mdpi.com/2072-6694/13/7/1531
dc.relation.isPartOfCancers (Basel)
dc.rights(c) 2021 The Author/s
dc.rightsCC BY 4.0
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectTP53 isoforms
dc.subjectalternative splicing
dc.subjectbreast cancer prognosis
dc.subjectlong amplicon digital PCR
dc.titleBreast Cancer Patient Prognosis Is Determined by the Interplay between TP53 Mutation and Alternative Transcript Expression: Insights from TP53 Long Amplicon Digital PCR Assays
dc.typeJournal article
pubs.elements-id500036
pubs.organisational-groupOther
Files
Original bundle
Now showing 1 - 3 of 3
Thumbnail Image
Name:
500036 PDF.pdf
Size:
3.52 MB
Format:
Adobe Portable Document Format
Description:
Evidence
Download
Thumbnail Image
Name:
Supp_Figures 500036.pdf
Size:
359.86 KB
Format:
Adobe Portable Document Format
Description:
Evidence
Download
Thumbnail Image
Name:
Supplementary Tables 500036.pdf
Size:
200.36 KB
Format:
Adobe Portable Document Format
Description:
Evidence
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
9.22 KB
Format:
Plain Text
Description:
Download
Collections
Journal Articles