Somatic Mosaicism of Androgen Receptor CAG Repeats in Colorectal Carcinoma Epithelial Cells From Men

Fabio, Francesco Di; Alvarado, Carlos; Gologan, Adrian; Youssef, Emad; Voda, Linda; Mitmaker, Elliot J.; Beitel, Lenore K.; Gordon, Philip H.; Trifiro, Mark

doi:10.1016/j.jss.2008.05.013

Cited by 6 publications

(5 citation statements)

References 27 publications

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“…Table S2). These include female breast cancer (MIM# 114480), CaP, uterine and endometrial cancer (MIM# 608089), all of which have been reviewed by Rajender et al (2007); colorectal cancer [Di Fabio et al, 2009; Ferro et al, 2002]; esophageal cancer (MIM# 133239) [Dietzsch et al, 2003]; and head and neck cancers (MIM# 275355) [dos Santo et al, 2004]. Other noncancer diseases include male infertility, bone and mineral density, reviewed by Rajender et al (2007)]; acne, hirsutism, and alopecia [Sawaya and Shalita, 1998]; endometriosis (MIM# 131200) [Shaik et al, 2009] and uterine leiomyoma (MIM# 150699) [Shaik et al, 2009]; Alzheimer's disease (MIM# 104300) [Lehman et al, 2003]; arthritis (MIM# 180300) [Kawasaki et al, 1999]; platelet reactivity [Kuliczkowski et al, 2010]; hypertension (MIM# 145500) [Pausova et al, 2010]; muscle and adipose tissue changes [Nielsen et al, 2010]; autism (MIM# 209850) [Henningsson et al, 2009]; personality traits [Westberg et al, 2009]; and violent criminal behavior [Rajender et al, 2008].…”

Section: Database Informationmentioning

confidence: 99%

The androgen receptor gene mutations database: 2012 update

et al. 2012

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Section: Database Informationmentioning

confidence: 99%

The androgen receptor gene mutations database: 2012 update

et al. 2012

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“…The AR gene contains polymorphic trinucleotide CAG repeats demonstrated to inversely affect receptor transcriptional activity [ 31 , 32 ]. Multiple somatic mutations of AR CAG repeats in colorectal carcinoma and adjacent normal mucosa, independent of MSI status, have been reported [ 33 ]. In a case-control study, the absence of AR expression and increasing length CAG repeats was associated with reduced 5-year overall survival in patients with CRC [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Spatial expression of IKK-alpha is associated with a differential mutational landscape and survival in primary colorectal cancer

et al. 2022

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Background To understand the relationship between key non-canonical NF-κB kinase IKK-alpha(α), tumour mutational profile and survival in primary colorectal cancer. Methods Immunohistochemical expression of IKKα was assessed in a cohort of 1030 patients who had undergone surgery for colorectal cancer using immunohistochemistry. Mutational tumour profile was examined using a customised gene panel. Immunofluorescence was used to identify the cellular location of punctate IKKα expression. Results Two patterns of IKKα expression were observed; firstly, in the tumour cell cytoplasm and secondly as discrete ‘punctate’ areas in a juxtanuclear position. Although cytoplasmic expression of IKKα was not associated with survival, high ‘punctate’ IKKα expression was associated with significantly reduced cancer-specific survival on multivariate analysis. High punctate expression of IKKα was associated with mutations in KRAS and PDGFRA. Dual immunofluorescence suggested punctate IKKα expression was co-located with the Golgi apparatus. Conclusions These results suggest the spatial expression of IKKα is a potential biomarker in colorectal cancer. This is associated with a differential mutational profile highlighting possible distinct signalling roles for IKKα in the context of colorectal cancer as well as potential implications for future treatment strategies using IKKα inhibitors.

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“…In line with previous studies addressing the relationship between FT, the CAG-RL, and depression severity [e.g., ( 11 – 13 )], the analysis of the AR was based on whole blood samples. Interestingly, in certain neurodegenerative diseases ( 44 , 45 ), in colorectal cancer ( 46 ) as well as in a transgenic animal models to study Huntington's disease ( 47 ), somatic mosaicism of CAG repeat length variation has been found. However, we are not aware that a CAG-RL mosaicism has been described in human blood DNA outside the named, specific diseases and animal disease models.…”

Section: Discussionmentioning

confidence: 99%

Size Matters: The CAG Repeat Length of the Androgen Receptor Gene, Testosterone, and Male Adolescent Depression Severity

et al. 2021

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There is a distinct increase in the prevalence of depression with the onset of puberty. The role of peripubertal testosterone levels in boys in this context is insufficiently understood and may be modulated by a functional polymorphism of the androgen receptor gene (AR), a variable number of CAG repeats. Moreover, there is preliminary evidence that the relationship between testosterone, CAG repeat length, and the severity of depressive symptoms may differ between subclinical and overt depression, but this has neither been studied in a clinical sample of adolescents with depression nor compared between subclinical and overt depression in an adequately powered study. To investigate the relationship between free testosterone, CAG repeat length of the AR, depression status (subclinical vs. overt), and the severity of depressive symptoms, 118 boys treated as in- or daycare patients at a single psychiatric hospital were studied. Of these, 73 boys had at least mild depressive symptoms according to the Beck Depression Inventory-II (BDI-II > 13). Higher-order moderation analysis in the multiple regression framework revealed a constant relationship between free testosterone and depression severity irrespective of the number of CAG repeats in adolescents with a BDI-II score ≤ 13. In adolescents with a BDI-II score > 13, however, there was a significant negative relationship between free testosterone and BDI-II score in patients with <19 CAG repeats and a significant positive relationship regarding free testosterone and BDI-II score in those with more than 28 CAG repeats, even when considering important covariates. These results suggest that the effects of testosterone on mood in male adolescents with depression depend on the genetic make-up of the AR as well as on depression status. This complex relationship should be considered by future studies addressing mental health issues against an endocrine background and may, moreover, contribute to tailored treatment concepts in psychiatric medicine, especially in adults.

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Somatic Mosaicism of Androgen Receptor CAG Repeats in Colorectal Carcinoma Epithelial Cells From Men

Cited by 6 publications

References 27 publications

The androgen receptor gene mutations database: 2012 update

The androgen receptor gene mutations database: 2012 update

Spatial expression of IKK-alpha is associated with a differential mutational landscape and survival in primary colorectal cancer

Size Matters: The CAG Repeat Length of the Androgen Receptor Gene, Testosterone, and Male Adolescent Depression Severity

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