TY - JOUR
T1 - Genetic alterations in hepatocellular carcinomas
T2 - Association between loss of chromosome 4q and p53 gene mutations
AU - Rashid, A.
AU - Wang, J. S.
AU - Qian, G. S.
AU - Lu, B. X.
AU - Hamilton, S. R.
AU - Groopman, J. D.
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
KW - Aflatoxin
KW - Hepatitis B virus
KW - Hepatocellular carcinomas
KW - Loss of heterozygosity
KW - p53 gene
UR - http://www.scopus.com/inward/record.url?scp=0142199720&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0142199720&partnerID=8YFLogxK
U2 - 10.1038/sj.bjc.6690321
DO - 10.1038/sj.bjc.6690321
M3 - Article
C2 - 10389978
AN - SCOPUS:0142199720
SN - 0007-0920
VL - 80
SP - 59
EP - 66
JO - British journal of cancer
JF - British journal of cancer
IS - 1-2
ER -