Kennedy disease in two sisters with biallelic CAG expansions of the androgen receptor gene

AbstractCarcinomas with apocrine differentiation (CAD) of the breast are rare tumours typically presenting high immunohistochemical expression of androgen receptor (AR) which is a target molecule for personalised therapy. To date, no studies have evaluated the genetic changes that are associated with AR immunohistochemical expression in CADs. The present work aims to characterise AR status in CADs. Twenty CAD tumours were studied with immunohistochemistry, in situ fluorescence hybridization and DNA methylation analysis, to evaluate AR expression and its regulator status. All tumours demonstrated high AR immunohistochemical expression, with over 95% of the neoplastic cells showing AR positivity in 19/20 cases. CADs showed AR gene copy loss in a percentage of neoplastic cells ranging from 5 to 84% (mean 48.93%). AR regulator genes, including the MAGE family, UXT and FLNA, presented variable methylation levels, but were mainly hypomethylated and therefore all transcriptionally active. The results of this study indicate that CADs present AR monosomy, paralleled by higher transcriptional activity of the gene with potential to influence response to AR deprivation therapy.

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Analysis of the CAG tract length in the Androgen Receptor gene in Mexican patients with nonsyndromic cryptorchidism

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2020-0378 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Daniel A. Landero-Huerta ◽

Rosa M. Vigueras-Villaseñor ◽

Lucía Taja-Chayeb ◽

Fabiola García-Andrade ◽

Elena Aréchaga-Ocampo ◽

...

Keyword(s):

Androgen Receptor ◽

Germ Cell ◽

Receptor Gene ◽

Germ Cell Tumors ◽

Androgen Receptor Gene ◽

Testicular Descent ◽

Healthy Individuals ◽

Testicular Germ Cell ◽

Molecular Alteration ◽

Mexican Patients

Abstract Objectives Cryptorchidism is the most common genitourinary birth defect in live newborn males and is considered as an important risk factor for testicular germ cell tumors and infertility. The Androgen Receptor gene is important in this pathology due to its participation, mainly, in the inguinoscrotal phase of testicular descent. We determine the length of the CAG tract in the Androgen Receptor (AR) gene in Mexican patients with nonsyndromic cryptorchidism. Methods One hundred and 15 males were included; of these, 62 had nonsyndromic cryptorchidism and 53 were healthy volunteers. DNA was extracted from a peripheral blood samples, subsequently, the CAG tract in exon 1 of AR gene was amplified by PCR and sequenced. Results Mexican patients with nonsyndromic cryptorchidism presented 25.03 ± 2.58 repeats of CAG tract in the AR gene compared to 22.72 ± 3.17 repeats of CAG tract in Mexican healthy individuals (p≤0.0001; t value of 4.3). Furthermore, the deletion of codon 57 that corresponds to the deletion of a leucine residue at position 57 (Del L57) in the AR gene was found for the first time in a nonsyndromic cryptorchidism patient. This molecular alteration has been related previously to testicular germ cell tumor (TGCT). Conclusions The CAG tract in the AR gene is longer in patients with nonsyndromic cryptorchidism than in healthy individuals, supporting the association between this polymorphism of the AR gene and nonsyndromic cryptorchidism in the Mexican population.

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