Loss of heterozygosity and analysis of mutation of p53 in hepatocellular carcinoma

Abstract

Thirty-six hepatocellular carcinoma (HCC) tissues obtained from 34 patients were classified according to histological diagnosis into six well-differentiated HCC, 20 moderately differentiated HCC and 10 poorly differentiated HCC. High molecular weight DNA was prepared from each tumour and the corresponding non-tumour tissue. Loss of heterozygosity (LOH) on chromosomes 4q, 5q, 10q, 11p, 16q, 17p, mutation of the p53 gene and polymorphism of intron 25 of the retinoblastoma (RB) gene were simultaneously analysed. The patients were composed of three cases of small HCC (the diameter of which was < 3 cm) and 31 cases of advanced HCC. Twenty-nine of 34 (85.3%) patients analysed had been exposed to hepatitis B virus and/or hepatitis C virus. The frequencies of LOH on seven chromosomes were 57.9% in 17p13.3, 45.1% in 17p, 45.1% in 11p, 41.9% in 5q, 41.9% in 16q24, 29.0% in 4q, 25.8% in 10q in advanced HCC (four of well differentiated, 18 of moderately differentiated and nine of poorly differentiated carcinoma). In contrast, LOH was observed on 4q, 5q, 16q and 17p in 33% (1/3) of the small HCC (two of well differentiated and one of moderately differentiated carcinoma). The mutation of the p53 genes and polymorphism of the RB gene were present in 25.8% (8/31) and 12.9% (4/31) of the advanced tumours, respectively, but the mutation was not found in small HCC. LOH on every chromosome and the p53 mutation were observed more frequently in more advanced tumours, and the genetic changes accumulated with the increase of the histopathological grade.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of DNA copy number aberrations in hepatitis C virus-associated hepatocellular carcinomas by conventional CGH and array CGH

“…Although loss of p53 has been reported in HCC. [19][20][21] and other solid tumors, it was rare in the present series. Our results indicate that loss of p53 is not a primary factor in the development of HCV-HCC and that other genes on 17p are involved in hepatocellular carcinogenesis.…”

Deletion mapping of chromosome 16q in hepatocellular carcinoma

“…The association between allelic loss on chromosome 16q and the progression of human HCC has been proposed by several groups (Tsuda et al, 1990;Nishida et al, 1992;Yumoto et al, 1995). Tsuda et al (1990) reported that allelic loss between HP and CTRB loci occurred more frequently in HCCs of poor differentiation and large size, and with metastasis.…”

“…Twenty-four (58.5%) HCCs were detected in cirrhotic livers. Nine cases (22%) were small (≤ 3 cm) and 32 (78%) were advanced (> 3 cm) HCCs (Yumoto et al, 1995). Tumour differentiation was graded according to the criteria of Kanai et al (1987): seven (17%) HCCs were well-differentiated, 23 (56%) were moderately differentiated and 11 (27%) were poorly differentiated according to this grading system.…”

Failure to detect genetic alteration of the mannose-6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) gene in hepatocellular carcinomas in japan

“…5,6 Many studies on HCCs have shown LOH on chromosomes 1p, 1q, 4q, 5q, 8p, 11p, 13q, 16q, and 17p. 7 In particular, the LOH and mutations of the RB gene on chromosome 13q and the P53 gene on 17p are frequently found. 7,8,9 However, such genetic changes have been reported to occur mainly in the late stage of hepatocarcinogenesis.…”

“…7 In particular, the LOH and mutations of the RB gene on chromosome 13q and the P53 gene on 17p are frequently found. 7,8,9 However, such genetic changes have been reported to occur mainly in the late stage of hepatocarcinogenesis. If genetic changes of M6P/IGF2R gene occur in early hepatic neoplasms, they would be extremely important because they could serve as a useful marker for differential diagnosis of small hepatic lesions, especially with biopsy samples.…”