Journal article
Biallelic TP53 gain of function mutations in rapidly progressing solid tumors
Cancer genetics, Vol.222-223, pp.20-24
04/2018
DOI: 10.1016/j.cancergen.2018.02.001
PMID: 29666004
Abstract
•Two cases with biallelic gain of function TP53 mutations as the sole abnormality.•The GOF mutations were associated with nuclear accumulation of the p53 protein.•Implementation of TP53 mutation analysis clinically may predict patient outcome.
Recent studies are discovering TP53 mutations with gain of function (GOF) properties that promote tumorigenesis via a variety of mechanisms. To our knowledge, all reported compound mutations are allelic. We identified two patients with biallelic GOF TP53 mutations in their tumors and a third with allelic compound variants. The correlation with p53 expression was also examined. Genomic DNA was extracted from formalin-fixed, paraffin-embedded tissue and mutational analysis was performed using Ion AmpliSeq™Cancer HotSpot Panel V2. Biallelic GOF mutations (p.R273H and p.R273C) were identified in a 19-year-old male with glioblastoma (allele frequencies 94% and 48%) and a 54-year-old with pT3 penile squamous cell carcinoma (allele frequencies 19% and 27%). Immunohistochemistry showed nuclear accumulation of p53. The third patient, a 62-year-old female with metastatic lung adenocarcinoma, had allelic p.P278S (GOF) and p.R283L (non-GOF) variants at frequencies of 61% but with null staining for p53. Germline testing for Patient 1 confirmed wildtype TP53. No other variants were discovered among the genes tested in these cases. All patients succumbed within two years of diagnosis despite aggressive treatment. In conclusion, implementation of TP53 mutation analysis in clinical practice may predict patient outcome, and inhibition of GOF p53 could represent an attractive target for therapy.
Details
- Title: Subtitle
- Biallelic TP53 gain of function mutations in rapidly progressing solid tumors
- Creators
- Christopher M Sande - Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City 52241, IA, USABrian Chang - Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City 52241, IA, USAVarun Monga - Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City 52241, IA, USAAaron D Bossler - Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City 52241, IA, USADeqin Ma - Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City 52241, IA, USA
- Resource Type
- Journal article
- Publication Details
- Cancer genetics, Vol.222-223, pp.20-24
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.cancergen.2018.02.001
- PMID
- 29666004
- ISSN
- 2210-7762
- eISSN
- 2210-7770
- Language
- English
- Date published
- 04/2018
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Pathology; Internal Medicine
- Record Identifier
- 9984047861802771
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