Distribution of a single nucleotide polymorphism on codon 211 of the androgen receptor gene and its correlation with human renal cell cancer in Japanese patients

Complete androgen insensitivity syndrome is caused by X chromosome linked disorder resulting in a target organ insensitivity to androgen. Two variants have been described in this syndrome. In the first, the binding of [3H] dihydrotestosterone(17β-hydroxy-5α-androstan-3-one) to the androgen receptor is undetectable (receptor-negative), whereas in the second variant normal levels of androgen receptor are detectable but the binding of [3H] dihydrotesterone to the androgen receptor is significantly thermolabile under certain conditions (receptor-positive). In receptor-negative cases, genetic disorders of the androgen receptor gene have been demonstrated. On the other hand, the genetic disorder of androgen receptor in receptor-positive cases is little known. In this study, the gene structure of androgen receptor in a receptor-positive case using a polymerase chain reaction technique is studied in the fibroblasts cultured from genital skin. The results demonstrate that the substitution of nucleotide (guanine→cytosine) in exon G of the androgen receptor causes the replacement of an amino acid in position 820 (glycine→alanine) which occurs in the hormone-binding domain of the androgen receptor. The substitution of nucleotide may explain the thermolability of the androgen receptor in a case with receptor-positive androgen insensitivity syndrome.

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Validation of the Correlation Between Single Nucleotide Polymorphism rs307826 in VEGFR3 and Outcome in Metastatic Clear-Cell Renal Cell Carcinoma Patients Treated with Sunitinib

Kidney Cancer ◽

10.3233/kca-200086 ◽

2020 ◽

Vol 4 (3) ◽

pp. 139-149

Author(s):

Benoit Beuselinck ◽

Thomas Van Brussel ◽

Annelies Verbiest ◽

Maxime Vanmechelen ◽

Gabrielle Couchy ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Single Nucleotide Polymorphism ◽

Cell Carcinoma ◽

Renal Cell ◽

Validation Cohort ◽

Clear Cell ◽

Nucleotide Polymorphism ◽

Discovery Cohort ◽

Cell Renal Cell Carcinoma ◽

Single Nucleotide

BACKGROUND: Previously, we have shown a correlation between single nucleotide polymorphism (SNP) rs307826 in vascular endothelial growth factor receptor-3 (VEGFR3) and outcome in metastatic clear-cell renal cell carcinoma (m-ccRCC) patients treated with sunitinib. OBJECTIVE: We aimed to validate this finding in an independent patient series. METHODS: m-ccRCC patients receiving sunitinib as first-line targeted therapy were included in a validation cohort. Endpoints were response rate (RR), progression-free survival (PFS) and overall survival (OS). We also updated survival data of our discovery cohort as described previously. RESULTS: Eighty-four patients were included in the validation cohort. rs307826 AG/GG-carriers had a shorter PFS (8 versus 12 months, p = 0.04) and a trend towards a shorter OS (18 versus 27 months, p = 0.22) compared to AA-carriers. In the total series of 168 patients (from the discovery cohort, as described previously, and the validation cohort), rs307826 AG/GG-carriers had a poorer RR (29% versus 53%, p = 0.008), PFS (8 versus 15 months, p = 0.0002) and OS (22 versus 31 months, p = 0.004) compared to AA-carriers. rs307826 was independently associated with PFS and OS on multivariate analysis. CONCLUSION: VEGFR3 rs307826 seems to be associated with outcome on sunitinib in m-ccRCC. Its impact highlights the role of VEGFR3 in ccRCC pathogenesis and as a target of sunitinib.

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