Comprehensive analysis of CTNNB1 in adrenocortical carcinomas [Elektronisk resurs] Identification of novel mutations and correlation to survival
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Maharjan, Rajani (författare)
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Backman, Samuel (författare)
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Åkerström, Tobias (författare)
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Hellman, Per (författare)
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Björklund, Peyman (författare)
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Experimental Surgery Group (medarbetare)
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Experimental Surgery Group (medarbetare)
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Experimental Surgery Group (medarbetare)
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Uppsala universitet Medicinska och farmaceutiska vetenskapsområdet (utgivare)
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Uppsala universitet Medicinska och farmaceutiska vetenskapsområdet (utgivare)
- Publicerad: 2018
- Engelska.
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Ingår i: Scientific Reports. - 2045-2322. ; 8
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Sammanfattning
Ämnesord
Stäng
- The Wnt/β-Catenin signaling pathway is one of the most frequently altered pathways in adrenocortical carcinomas (ACCs). The aim of this study was to investigate the status of Wnt/β-Catenin signaling pathway by analyzing the expression level of β-Catenin and the mutational status of APC , AXIN2 , CTNNB1 , and ZNRF3 in ACCs. Mutations in APC , CTNNB1 , ZNRF3 and homozygous deletions in ZNRF3 were observed in 3.8% (2/52), 11.5% (6/52), 1.9% (1/52) and 17.3% (9/52) of the cohort respectively. Novel interstitial deletions in CTNNB1 spanning intron 1 to exon 3/intron 3 were also found in 7.7% (4/52) of the tumours. All the observed alterations were mutually exclusive. Nuclear accumulation of β-Catenin, increased expression of Cyclin D1 and significantly higher expression of AXIN2 (p = 0.0039), ZNRF3 (p = 0.0032) and LEF1(p = 0.0090) observed in the tumours harbouring the deletion in comparison to tumours without CTNNB1 mutation demonstrates that the truncated β-Catenin is functionally active and erroneously activates the downstream targets. Significantly lower overall survival rate in patients with tumours harbouring alterations in APC / CTNNB1 / ZNRF3 in comparison to those without mutation was observed. In conclusion, the discovery of novel large deletions in addition to the point mutations in CTNNB1 infers that activation of Wnt/β-Catenin pathway via alterations in CTNNB1 occurs frequently in ACCs. We also confirm that alterations in Wnt/β-Catenin signaling pathway members have a negative effect on overall survival of patients.
Ämnesord
- Medical and Health Sciences (hsv)
- Basic Medicine (hsv)
- Cell and Molecular Biology (hsv)
- Medicin och hälsovetenskap (hsv)
- Medicinska och farmaceutiska grundvetenskaper (hsv)
- Cell- och molekylärbiologi (hsv)
- Medical and Health Sciences (hsv)
- Clinical Medicine (hsv)
- Cancer and Oncology (hsv)
- Medicin och hälsovetenskap (hsv)
- Klinisk medicin (hsv)
- Cancer och onkologi (hsv)
- Molekylär genetik (uu)
- Molecular Genetics (uu)
- Endocrinology and Diabetology (uu)
- Endokrinologi och Diabetologi (uu)
Indexterm och SAB-rubrik
- adrenocortical carcinomas
- CTNNB1
- mutation
- β-Catenin
- survival
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