Somatic mutations at the trinucleotide repeats of androgen receptor gene in male hepatocellular carcinoma
Journal
International Journal of Cancer
Journal Volume
120
Journal Issue
8
Pages
1610-1617
Date Issued
2007
Author(s)
Abstract
Androgen and androgen receptor (AR) have long been implicated in liver carcinogenesis, especially for the male dominance feature. However, whether AR gene could occur in somatic mutations that might contribute to this process has not yet been studied. DNA sequencing and genotyping were conducted for detecting the genetic aberrations of AR gene in 257 primary hepatocellular carcinomas (HCCs) and also the dysplastic nodules (DN) from another 11 patients. Twenty-one AR somatic mutations causing amino acid changes were identified in HCC and even in the pre-cancerous DN. The missense somatic mutations of AR were rare in HCC (2 cases) but the trinucleotide repeat (TNR) changes, both at (CAG)n and (GGC)n, was a more common one (19 cases). Notably, all these mutations occurred in male patients and most TNR changes belonged to the contraction type (15 out of 19 cases, 78.9%), which has been reported to associate with increased AR transcriptional activity. Most samples with TNR changes did not show microsatellite instability, suggesting a different cause for these TNR mutations. Although no significant correlation was identified between AR mutations and the clinicopathologic parameters, we found the (CAG)n length significantly shorter in hepatitis B virus (HBV)(+) HCCs than in HBV(-) HCCs and the (GGC)n length significantly correlates with the overall survival. In conclusion, the mis-sense somatic mutations of AR were rare in HCC but the TNR change was a more common one, which exclusively occurred in males. Moreover, the length of TNR carried clinical significance in special HCC group. ? 2007 Wiley-Liss, Inc.
SDGs
Other Subjects
androgen; androgen receptor; adult; article; controlled study; DNA sequence; female; genetic transcription; genotype; Hepatitis B virus; Hepatitis C virus; human; human cell; human tissue; liver carcinogenesis; liver cell carcinoma; major clinical study; male; microsatellite instability; missense mutation; nucleotide sequence; precancer; priority journal; receptor gene; sex difference; somatic mutation; trinucleotide repeat
Publisher
Wiley-Liss Inc.
Type
journal article