Abnormal nucleotide repeat sequence in the TGF-betaRII gene in hepatocellular carcinoma and in uninvolved liver tissue.
Replication error (RER)-related genetic alterations are associated with a subset of hepatocellular carcinomas (HCCs) with multiple primary cancers. This study investigated whether mutations in the nucleotide repeats of three putative target genes of RER are associated with hepatocarcinogenesis. The genes examined were those encoding transforming growth factor beta type II receptor (TGF-betaRII), BCL-2-associated X protein (BAX), and insulin-like growth factor II receptor (IGF-IIR). Tumour and non-tumour hepatic tissues were examined in 48 HCC patients, 34 with solitary HCC and 14 who had double cancer with gastric cancer. Four double-cancer cases showed an abnormal signal in the single nucleotide repeat (A)10 of the TGF-betaRII gene. These four were among the six RER-positive cases in this series. The genotypes of the poly A tract of the TGF-betaRII gene in the liver tumour tissue of the four cases with an abnormal signal were (A)9/10, (A)9/10, (A)9/10, and (A)9/9. Five uninvolved liver tissue specimens from these four patients showed (A)9/10 and (A)9/9, (A)9/10, (A)10/10 and (A)9/9, respectively. The genotype in the stomach cancer specimens of these four patients was (A)10/10, indicating no germline mutation of the TGF-betaRII gene. There were no mutations in the nucleotide repeats of the BAX and IGF-IIR genes in any of the liver tissue specimens. Abnormality of the nucleotide repeat in the TGF-betaRII gene occurred in the uninvolved liver tissue as well as the HCC tissue in some HCC patients. Such genetic instability may be gene-specific and tissue-specific in carcinogenesis.
Enomoto
A
A
Department of Pathology, Nihon University School of Medicine, Tokyo 173-8610, Japan.
Esumi
M
M
Yamashita
K
K
Takagi
K
K
Takano
S
S
Iwai
S
S
D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D018895:Microsatellite Repeats; D009154:Mutation; D009378:Neoplasms, Multiple Primary / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger / Q000032:analysis; D017527:Receptor, IGF Type 2 / Q000235:genetics; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D017527:Receptor, IGF Type 2; D018125:Receptors, Transforming Growth Factor beta; D051028:bcl-2-Associated X Protein; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II