2010
DOI: 10.1158/1541-7786.mcr-10-0086
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Mutations in the Circadian Gene CLOCK in Colorectal Cancer

Abstract: The circadian clock regulates daily variations in physiologic processes. CLOCK acts as a regulator in the circadian apparatus controlling the expression of other clock genes, including PER1. Clock genes have been implicated in cancer-related functions; in this work, we investigated CLOCK as a possible target of somatic mutations in microsatellite unstable colorectal cancers. Combining microarray gene expression data and public gene sequence information, we identified CLOCK as 1 of 790 putative novel microsatel… Show more

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Cited by 75 publications
(61 citation statements)
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“…Because mutations in protein-coding genes are considered to be a causative factor in carcinogenesis (Ionov et al 1993;Markowitz et al 1995;Perucho 1996;Rampino et al 1997;Alhopuro et al 2010), we filtered MS mutations in gene regions (both coding sequences [CDSs] and UTRs) from the identified total deletions (Supplemental Table S2, S3). The number of deletion mutations in gene regions was four-to sixfold higher in MSI-H gastric cancer cell lines and primary tissues than MSS samples.…”
Section: Comprehensive Distribution Of Ms Mutations With Deletion Thrmentioning
confidence: 99%
“…Because mutations in protein-coding genes are considered to be a causative factor in carcinogenesis (Ionov et al 1993;Markowitz et al 1995;Perucho 1996;Rampino et al 1997;Alhopuro et al 2010), we filtered MS mutations in gene regions (both coding sequences [CDSs] and UTRs) from the identified total deletions (Supplemental Table S2, S3). The number of deletion mutations in gene regions was four-to sixfold higher in MSI-H gastric cancer cell lines and primary tissues than MSS samples.…”
Section: Comprehensive Distribution Of Ms Mutations With Deletion Thrmentioning
confidence: 99%
“…Furthermore, genetic disruption of the circadian signalling pathways may be a factor behind disease-development in humans (131)(132)(133). Particularly in cancer cells, which have an unstable genome, mutations in the circadian clock genes are not uncommon (133,134), and therefore the circadian clock could be locally Figure 2 Scheme indicating our hypothesis on how disruptions in circadian rhythmicity increase the risk of disease, alternatively poorer response to treatment. Various types of circadian disruption such as shift-work, jet-lag, sleep disorders or genetic polymorphisms negatively affect important physiological functions, including rhythm generation by the central pacemaker in the SCN, metabolism, immune function, physical activity, cardiovascular functions and intestinal functions.…”
Section: Discussionmentioning
confidence: 98%
“…Also other types of sleep disorders as well as stress and worries brought about increasing demands from the society on our personal performance may influence the circadian clock and cause disease (130). Furthermore, genetic disruption of the circadian signalling pathways may be a factor behind disease-development in humans (131)(132)(133). Particularly in cancer cells, which have an unstable genome, mutations in the circadian clock genes are not uncommon (133,134), and therefore the circadian clock could be locally Figure 2 Scheme indicating our hypothesis on how disruptions in circadian rhythmicity increase the risk of disease, alternatively poorer response to treatment.…”
Section: Discussionmentioning
confidence: 99%
“…13 Many of these genes also seem to contribute to the relationship between sleep and psychiatric conditions. For example, the transcription factor clock regulates the expression of numerous other circadian genes.…”
Section: Illuminating Sleep's Pathwaysmentioning
confidence: 99%
“…For example, the transcription factor clock regulates the expression of numerous other circadian genes. 13 Certain CLOCK variants seem to increase the risk of early, middle and late insomnia as well as influencing changes in sleep patterns during treatment with antidepressants. PER3 polymorphisms are associated with worse mood in the evening and DSPS.…”
Section: Illuminating Sleep's Pathwaysmentioning
confidence: 99%