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Prognostic signific...
Prognostic significance of homozygous deletions and multiple duplications at the CDKN2A (p16INK4a)/ARF (p14ARF) locus in urinary bladder cancer
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- Berggren de Verdier, P. J. (författare)
- Karolinska Institutet,Karolinska University Hospital
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- Kumar, R. (författare)
- Karolinska Institute
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- Adolfsson, J. (författare)
- Karolinska Institutet,Karolinska Institute
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- Larsson, P. (författare)
- Karolinska University Hospital
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- Norming, U. (författare)
- Karolinska Institutet,Stockholm South Hospital
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- Onelov, E. (författare)
- Karolinska Institutet,Karolinska University Hospital
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- Wijkstrom, H. (författare)
- Karolinska University Hospital
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- Steineck, Gunnar, 1952 (författare)
- Karolinska Institutet,Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper,Institute of Clinical Sciences,Karolinska University Hospital
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- Hemminki, K. (författare)
- Karolinska Institute
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(creator_code:org_t)
- Informa UK Limited, 2006
- 2006
- Engelska.
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Ingår i: Scand J Urol Nephrol. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 40:5, s. 363-9
- Relaterad länk:
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https://gup.ub.gu.se...
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http://kipublication...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- OBJECTIVE: The 9p21 locus is a major target in the pathogenesis of human urinary bladder cancer. This locus harbours the CDKN2A/ARF tumour suppressor gene, which encodes two cell-cycle regulatory proteins: p16INK4a and p14ARF. We studied how homozygous deletions and multiple duplications at this locus affect prognosis and survival in patients with bladder cancer. MATERIAL AND METHODS: Real-time quantitative polymerase chain reaction (QPCR), based on simultaneous amplification of ARF and a reference gene, glyceraldehyde-3-phosphate dehydrogenase, was used to measure homozygous deletions and multiple duplications in a population-based material consisting of 478 patients with urinary bladder cancer. Results from real-time QPCR were compared with clinico-pathological parameters and survival curves were generated using the Kaplan-Meier method. RESULTS: Real-time QPCR analysis showed 71 (15%) homozygous deletions and 8 (2%) multiple duplications. We were unable to find any association between either stage or grade and urinary neoplasms with homozygous deletions. However, although there were only a limited number of patients with multiple duplications, 7/8 of them had highly malignant tumours (G2b-G4 or > or = T1; p = 0.02). CONCLUSIONS: Urinary bladder cancers constitute a spectrum of neoplasms with varying clinical manifestations. We were unable to establish a prognostic relevance for patients with tumours harbouring homozygous deletions at the CDKN2A/ARF locus. However, our data did indicate that patients with multiple duplications at the CDKN2A/ARF locus had poor survival. This suggests that multiple duplications, in combination with other genetic changes, have cooperative effects which have a negative outcome on urinary bladder cancer prognosis.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- Carcinoma
- Transitional Cell/*genetics/mortality/pathology
- Chromosomes
- Human
- Pair 9/genetics
- Cohort Studies
- Cyclin-Dependent Kinase Inhibitor p16/*genetics
- Gene Deletion
- Gene Duplication
- Humans
- Loss of Heterozygosity/genetics
- Neoplasm Staging
- Polymerase Chain Reaction
- Prognosis
- Tumor Suppressor Protein p14ARF/*genetics
- Urinary Bladder Neoplasms/*genetics/mortality/pathology
- MEDICINE
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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