Frequency of KLK3 gene deletions in the general population

Background One of the kallikrein genes ( KLK3) encodes prostate-specific antigen, a key biomarker for prostate cancer. A number of factors, both genetic and non-genetic, determine variation of serum prostate-specific antigen concentrations in the population. We have recently found three KLK3 deletio...

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Vydáno v:Annals of clinical biochemistry Ročník 54; číslo 4; s. 472
Hlavní autoři: Rodriguez, Santiago, Al-Ghamdi, Osama A, Guthrie, Philip Ai, Shihab, Hashem A, McArdle, Wendy, Gaunt, Tom, Alharbi, Khalid K, Day, Ian Nm
Médium: Journal Article
Jazyk:angličtina
Vydáno: England 01.07.2017
Témata:
Biomarkers, Tumor - genetics
Cohort Studies
False Negative Reactions
Gene Deletion
Gene Expression
Heterozygote
Humans
Kallikreins - deficiency
Kallikreins - genetics
Male
Middle Aged
Monitoring, Physiologic
Mutation Rate
Prognosis
Prostate-Specific Antigen - deficiency
Prostate-Specific Antigen - genetics
Prostatic Neoplasms - diagnosis
Prostatic Neoplasms - genetics
Prostatic Neoplasms - pathology
KLK3
amplification ratiometry control system
PennCNV
deletions
prostate-specific antigen
ISSN:1758-1001, 1758-1001
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Shrnutí:Background One of the kallikrein genes ( KLK3) encodes prostate-specific antigen, a key biomarker for prostate cancer. A number of factors, both genetic and non-genetic, determine variation of serum prostate-specific antigen concentrations in the population. We have recently found three KLK3 deletions in individuals with very low prostate-specific antigen concentrations, suggesting a link between abnormally reduced KLK3 expression and deletions of KLK3. Here, we aim to determine the frequency of kallikrein gene 3 deletions in the general population. Methods The frequency of KLK3 deletions in the general population was estimated from the 1958 Birth Cohort sample ( n = 3815) using amplification ratiometry control system. In silico analyses using PennCNV were carried out in the same cohort and in NBS-WTCCC2 in order to provide an independent estimation of the frequency of KLK3 deletions in the general population. Results Amplification ratiometry control system results from the 1958 cohort indicated a frequency of KLK3 deletions of 0.81% (3.98% following a less stringent calling criterion). From in silico analyses, we found that potential deletions harbouring the KLK3 gene occurred at rates of 2.13% (1958 Cohort, n = 2867) and 0.99% (NBS-WTCCC2, n = 2737), respectively. These results are in good agreement with our in vitro experiments. All deletions found were in heterozygosis. Conclusions We conclude that a number of individuals from the general population present KLK3 deletions in heterozygosis. Further studies are required in order to know if interpretation of low serum prostate-specific antigen concentrations in individuals with KLK3 deletions may offer false-negative assurances with consequences for prostate cancer screening, diagnosis and monitoring.
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ISSN:1758-1001
1758-1001
DOI:10.1177/0004563216666999