Genetic alterations in hepatocellular carcinomas: association between loss of chromosome 4q and p53 gene mutations.
The major risk factors for hepatocellular carcinomas (HCC) in high incidence areas include infection with hepatitis B and C viruses (HBV, HCV) and exposure to aflatoxin. Genetic alterations in 24 liver resection specimens from Shanghai and Qidong were studied. Hepatitis B virus was integrated in all patient samples, and a null phenotype for the GSTM1 enzyme was present in 63% of patients. Alteration of p53 was present in 95% (23/24) of cases: mutations of the p53 gene in 12 HCC, p53 overexpression in 13 and loss of heterozygosity (LOH) of chromosome 17p in 17. All seven HCCs with a p53 mutation from Qidong and three of five from Shanghai had the aflatoxin-associated point mutation with a G to T transversion at codon 249, position 3. No HCC had microsatellite instability. LOH of chromosome 4q, 1p, 16q and 13q was present in 50%, 46%, 42% and 38%, respectively, and 4q was preferentially lost in HCCs containing a p53 mutation: LOH of 4q was present in 75% (9/12) of HCC with, but only 25% (3/12) of HCC without, a p53 gene mutation (P = 0.01). These data indicate a possible interaction between p53 gene mutation and 4q loss in the pathogenesis of HCC.
Rashid
A
A
Department of Pathology, The Johns Hopkins Oncology Center, The John Hopkins School of Medicine, Baltimore, MD 21205-2196, USA.
Wang
J S
JS
Qian
G S
GS
Lu
B X
BX
Hamilton
S R
SR
Groopman
J D
JD
D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology / Q000821:virology; D002681:China; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D004247:DNA / Q000032:analysis; D004851:Epoxide Hydrolases / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D006509:Hepatitis B / Q000150:complications / Q000175:diagnosis; D006511:Hepatitis B Antigens / Q000302:isolation & purification; D018936:Hepatitis C Antigens / Q000302:isolation & purification; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D009154:Mutation; D016133:Polymerase Chain Reaction
D004247:DNA; D004851:Epoxide Hydrolases; D005982:Glutathione Transferase; D006511:Hepatitis B Antigens; D018936:Hepatitis C Antigens