Mutations in the E2-PePHD region of hepatitis C virus type 1b in patients with hepatocellular carcinoma.
An interaction between the protein kinase (PKR)-eIF2-alpha phosphorylation homology domain (PePHD) within the E2 protein of hepatitis C virus (HCV) and cell protein kinase (PKR) may affect the control of protein synthesis and cell growth. In an attempt to investigate the genetic variability of the E2-PePHD domain in hepatocellular carcinoma (HCC), we studied sera and liver tissues from HCC patients. The partial E2-PePHD region was analysed by direct sequencing of the sera of 47 HCCs in cirrhotic livers and 31 cases of chronic active hepatitis (CAH), and tumoral and non-tumoral liver tissues from 13 HCC patients. A similar number of mutations was detected within the E2 domain in the HCC and CAH cases, but nine of the 47 HCCs (19%) showed an amino acid (aa) mutation at position 660, eight of which involved a change in the same aa (alanine instead of serine; A/S). No such mutation was detected in any of the PePHD sequences from the CAH patients: this difference was statistically significant (P = 0.008). The aa change at position 660 was also found in two sequences from tumoral but not non-tumoral tissue from the same liver. The analysis of 461 sequences obtained from GenBank supports the conclusion that the observed aa change is an infrequent event in HCV-infected patients, thus suggesting that it could be associated with HCC.
Bagaglio
S
S
Department of Infectious Diseases, San Raffaele, Scientific Institute, 20127 Milan, Italy.
De Mitri
M S
MS
Lodrini
S
S
Paties
C
C
Cassini
R
R
Bianchi
G
G
Bernardi
M
M
Lazzarin
A
A
Morsica
G
G
D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000821:virology; D036388:Ephrin-B2 / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000821:virology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011336:Probability; D012367:RNA, Viral / Q000032:analysis; D012680:Sensitivity and Specificity; D046509:Tissue Culture Techniques; D017361:Viral Nonstructural Proteins / Q000235:genetics
D036388:Ephrin-B2; D005819:Genetic Markers; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins