PMID- 10389978 OWN - NLM STAT- MEDLINE DCOM- 19990707 LR - 20181113 IS - 0007-0920 (Print) IS - 0007-0920 (Linking) VI - 80 IP - 1-2 DP - 1999 Apr TI - Genetic alterations in hepatocellular carcinomas: association between loss of chromosome 4q and p53 gene mutations. PG - 59-66 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. FAU - Rashid, A AU - Rashid A AD - Department of Pathology, The Johns Hopkins Oncology Center, The John Hopkins School of Medicine, Baltimore, MD 21205-2196, USA. FAU - Wang, J S AU - Wang JS FAU - Qian, G S AU - Qian GS FAU - Lu, B X AU - Lu BX FAU - Hamilton, S R AU - Hamilton SR FAU - Groopman, J D AU - Groopman JD LA - eng PT - Journal Article PL - England TA - Br J Cancer JT - British journal of cancer JID - 0370635 RN - 0 (Hepatitis B Antigens) RN - 0 (Hepatitis C Antigens) RN - 9007-49-2 (DNA) RN - EC 2.5.1.18 (Glutathione Transferase) RN - EC 2.5.1.18 (glutathione S-transferase M1) RN - EC 3.3.2.- (Epoxide Hydrolases) SB - IM MH - Carcinoma, Hepatocellular/*genetics/pathology/virology MH - China MH - Chromosomes, Human, Pair 17/genetics MH - Chromosomes, Human, Pair 4/*genetics MH - DNA/analysis MH - Epoxide Hydrolases/genetics MH - *Genes, p53/genetics MH - Glutathione Transferase/genetics MH - Hepatitis B/complications/diagnosis MH - Hepatitis B Antigens/isolation & purification MH - Hepatitis C Antigens/isolation & purification MH - Humans MH - Immunohistochemistry MH - Liver Neoplasms/*genetics/pathology/virology MH - *Loss of Heterozygosity MH - Microsatellite Repeats MH - Mutation MH - Polymerase Chain Reaction PMC - PMC2362990 EDAT- 1999/07/02 00:00 MHDA- 1999/07/02 00:01 CRDT- 1999/07/02 00:00 PHST- 1999/07/02 00:00 [pubmed] PHST- 1999/07/02 00:01 [medline] PHST- 1999/07/02 00:00 [entrez] AID - 10.1038/sj.bjc.6690321 [doi] PST - ppublish SO - Br J Cancer. 1999 Apr;80(1-2):59-66. doi: 10.1038/sj.bjc.6690321.