The role of previous infection of hepatitis B virus in Hbs antigen negative and anti-HCV negative Japanese patients with hepatocellular carcinoma: etiological and molecular biological study

The aim of this study is to elucidate the important role of the previous infection of HBV, and the relations among HBV genome integration and p53 gene mutation, telomerase activity and genetic instability in liver tissue with HBsAg-negative (NB) and anti-HCV negative (NC) hepatocellular carcinoma (HCC). We examined the backgrounds of 34 NB and NC (NBNC) Japanese patients with chronic liver disease (CLD) patients not associated with HCC and 26 NBNC CLD patients with HCC. HBV genome integration into host cell genome, p53 gene mutation telomerase activity and genetic instability were examined in 6 with NBNC HCC (NBNC-HCC) tumorous tissue (T) and non-tumorous tissues (NT). In the NBNC group, HBV-related antibody positive patients with HCC are significantly more than the patients without HCC. Moreover, concerning the stage of the coexisted liver diseases, in NBNC CLD, LC patients with HCC is 19 of 26 (73.1%) , on the other hand, LC patients without HCC is 16 of 34 (47.1%). LC patients with HCC group is significantly more than that without HCC. Three (50%) of 6 in T and 3 cases (50% ) in NT were found to integrated genome of HBV. p53 gene mutation was observed in 3 (50%) of T. Concerning the telomerase activity, 3 of 6 cases (50%) in T and 1 case in NT was recognized. There was no genetic instability (LOH or RER) of D2S123, D3S1067 and TP 53 in T and NT. Finally in T of NBNC HCC cases, TTVDNA was detected in 3 of 5. Even in the HBsAg-negative and anti-HCV negative HCC cases, CLD coexisting with LC, previous HBV infection and HBVDNA integration were observed. There were a few cases with HBVDNA integration, p53 gene mutation, telomerase activity and genetic instability, simultaneously in HCC tissue, and in some cases, the coexistence with TTVDNA were concurrently confirmed. It is speculated that the important role of the previous infection of HBV may have also been proposed for HCC oncogentic progression in NBNC CLD [corrected].     

Hepatitis B virus DNA integration frequently observed in the hepatocellular carcinoma DNA of hepatitis C virus-infected patients

Human hepatitis B virus (HBV) and hepatitis C virus (HCV) are two major etiologic agents of chronic hepatitis, which is closely related to the development of hepatocellular carcinoma (HCC). We investigated the role of HBV coinfection in ongoing HCV-related liver diseases in HCV-infected patients. We found a high prevalence of anti-HBc in anti-HCV-positive/HBsAg-negative HCC patients and also found a close correlation between anti-HBc positivity and integration of HBV DNA into HCC DNA of anti-HCV-positive/HBsAg-negative patients. The present data suggest that integrated HBV DNA may play an important role in the development of HCC in the anti-HCV-positive/HBsAg-negative patients carrying the anti-HBc antibody.     

p53 Gene mutation and genetic instability in superficial multifocal esophageal squamous cell carcinoma

Tumor multicentricity is occasionally observed in esophageal squamous cell carcinoma (SCC). We studied five surgically resected superficial multifocal esophageal SCCs for p53 gene mutation and genetic instability, using DNA extracted from microdissected areas. A total of 38 target areas (TAs) were analyzed in SCC, dysplasia, basal cell hyperplasia (BCH) and normal squamous epithelium. Analysis of the replication error (RER) at 10 microsatellite loci showed microsatellite instability in all TAs, as well as in normal squamous epithelium. p53 gene mutation was identified in 28.9% (11/38 TAs). All cases showed a common missense mutation in exon 8 at codon 273 (CGT-->CAT, Arg-->His), which was DNA contact mutation in the S10 beta strand. In association with microsatellite alterations, 7 of 9 TAs with p53 mutation in exon 8 at codon 273 also showed loss of heterozygosity (LOH) of p53 gene. LOH of p53 gene was detected in 83.8% (31/37 TAs). LOH at D2S123 on 2p16 near MSH2 gene and at D3S1611 on 3p22 near MLH1 gene was detected in 65.4% (17/26) and 71.4% (10/14) TAs, respectively. Frequencies of LOH at p53 and D2S123 were similar in non-cancerous areas and SCCs. LOH of p53 and D2S123 were found in 50% (5/10 TAs) of non-cancerous areas and 60% (9/15 TAs) of SCCs. Our results suggest that genetic instability induces esophageal tumor multicentricity, and that p53 gene contact mutation together with LOH are early events of the multistage carcinogenesis of multifocal primary esophageal SCC.     

宫颈癌患者基因组遗传不稳定性分析

目的 研究中国宫颈癌高发区宫颈癌患者基因组遗传不稳定性改变，为寻找宫颈癌相关内源因子提供依据。方法 从GenBank中选取8对微卫星DNA引物，采用PCR-变性PAGE-银染方法检测50例宫颈癌(来自高发区)活检组织及其对照(同病例血液)样品的杂合性丢失(LOH)和微卫星不稳定(MI)。结果 LOH总检出率为66％(33／50)，其中，D18S474(染色体18q21)LOH达40．5％；染色体3p21．2—3p21．3中微卫星位点D3S1478，LOH达31．7％；并且在原位癌与浸润癌中，LOH分布也有一定差异。MI在宫颈癌患者基因组中仅存在少数微卫星位点，总的发生率较低，为8％(4／50)。结论 除高危型人乳头瘤病毒(HPVhr)感染外，细胞内源基因的改变在宫颈癌发生发展过程中也起着重要作用。高频LOH位点18q21 D18S474、3p21．2-3p21．3 D3S1478可能存在潜在的宫颈癌抑癌基因。     

Microsatellite and chromosome instability in squamous cell laryngeal carcinoma.

Head-and neck squamous cell carcinoma (HNSCC) represents almost 5% of all malignancies in Europe. The aetiology of HNSCC is complex, with both genetic and mutagenic factors involved. The aim of the present study was to investigate the loss of heterozygosity (LOH), mainly at tumour suppressor loci (using markers D1S2883, D2S123, D3S1611, D5S346, D7S501, D8S254, TP53, NM23), microsatellite instability (BAT25, 26, 40) and (bleomycin test) in patients with squamous cell larynx cancer. In a group of 20 patients LOH was observed mainly at the loci 3p (64.7%), 8q (71.4%), 17q (M1-30.8%, M2-25%, M3-38.5%). Despite chromosomal instability detected by bleomycin no microsatellite instability was observed.     

Genetic heterogeneity of surgically resected prostate carcinomas and their biopsy specimens is related to their histologic differentiation

BACKGROUND: In human prostate carcinogenesis, many genetic analyses including conventional loss of heterozygosity (LOH) studies and microsatellite LOH analyses using the polymerase chain reaction method have revealed frequent LOH events at specific regions on chromosomes 3p, 7q, 8p, 10q, 16q, 17q, and 18q. METHODS: Using the laser-captured microdissection method, the authors extracted genomic DNA from 23 cases of prostate carcinomas including 59 different lesions and 8 biopsy specimens. Using (32)P-labeled primers, the authors analyzed six microsatellite loci (D3S647, D3S1228, D7S522, D8S137, NEFL, and D10S190) at which frequent LOH events have been reported. RESULTS: Of 10 cases in which the authors found LOH at any of the loci, 8 cases showed a heterogeneous LOH pattern. In four cases, the authors also found replication error (RER) at some of the loci examined. There was no significant relation between histologic differentiation and frequency of LOH or RER events. The overall LOH rate was found to be significantly lower in foci at classification pT2 (1 of 28 foci, 3%) compared with those at classification pT3 (13 of 44 foci, 30%). In pT3 samples, LOH events in extraglandular foci (9 of 23 foci, 39%) tended to be more frequent compared with those in intraglandular foci (8 of 41 foci, 20%). The patterns of LOH events in biopsy specimens correlated well with those in foci from surgical material showing the same histologic characteristics. CONCLUSIONS: Prostate carcinoma is a genetically multicentric carcinoma, and the genetic heterogeneity is well correlated with histologic differentiation. The frequency of LOH events increased according to the degree of tumor progression.     

Frequent microsatellite instability in lung cancer from chromate-exposed workers

Although chromium has been the most extensively investigated metal with respect to mutagenicity and carcinogenicity, its genetic effects in humans are only partly understood. Our previous study demonstrated that lung cancer from chromate-exposed workers infrequently (20%) displayed p53 gene mutations as well as a particular mutation pattern. In the present study, we examined the replication error (RER) and loss of heterozygosity (LOH) in 38 lung cancers from 28 chromate-exposed workers (chromate lung cancer group) and in 26 lung cancer patients without chromate exposure (non-chromate lung cancer group), using six microsatellite markers containing CA repeats: D3S647 (3p23), D3S966 (3p21.3), D3S1289 (3p21.1), D5S346 (5q21-q22), D9S161 (9p21), and TP53 (17p13.1). The RER phenotype was defined as the presence of microsatellite instability (MSI) at two or more loci. Thirty (78.9%) of 38 tumors in the chromate lung cancer group exhibited RER. In contrast, only four (15.4%) of 26 tumors in the non-chromate lung cancer group exhibited RER. The frequency of RER in the chromate lung cancer group was significantly higher than that in the non-chromate lung cancer group (P < 0.0001). By contrast, the frequency of LOH at 3p, 5q, 9p, and 17p loci in tumors with chromate exposure was not significantly different from that in tumors without chromate exposure. In the chromate lung cancer group, the period of chromate exposure in workers with RER (24.5 +/- 6.7 yr) was significantly longer than that in workers without RER (17.0 +/- 3.5 yr) (P = 0.0046). In addition, a longer period of chromate exposure was associated with a tendency toward a higher frequency of MSI. This finding suggests that MSI may play a role in chromium-induced carcinogenesis. In addition to our previous study of p53 mutations, the present findings suggest that the carcinogenic mechanism of chromate lung cancer may differ from that of non-chromate lung cancer.     

Prognostic value of replication errors on chromosomes 2p and 3p in non-small-cell lung cancer.

As chromosomes 2p and 3p are frequent targets for genomic instability in lung cancer, we have addressed whether alterations of simple (CA)n DNA repeats occur in non-small-cell lung cancer (NSCLC) at early stages. We have analysed by polymerase chain reaction (PCR) assay replication errors (RER) and loss of heterozygosity (LOH) at microsatellites mapped on chromosomes 2p and 3p in 64 paired tumour-normal DNA samples from consecutively resected stage I, II or IIIA NSCLC. DNA samples were also examined for K-ras and p53 gene mutations by PCR-single-stranded conformational polymorphism (PCR-SSCP) analysis and cyclic sequencing, as well as their relationship with clinical outcome. Forty-two of the 64 (66%) NSCLC patients showed RER at single or multiple loci. LOH was detected in 23 tumours (36%). Among patients with stage I disease, the 5-year survival rate was 80% in those whose tumours had no evidence of RER and 26% in those with RER (P = 0.005). No correlation was established between RER phenotype and LOH, K-ras or p53 mutations. RER remained a strong predictive factor (hazard ratio for death, 2.89; 95% confidence interval, 2.23-3.79; P = 0.002) after adjustment for all other evaluated factors, including p53, K-ras, LOH, histological type, tumour differentiation and TNM stage, suggesting that microsatellite instability on chromosomes 2p and 3p may play a role in NSCLC progression through a different pathway from the traditional tumour mechanisms of oncogene activation and/or tumour-suppressor gene inactivation.     

Hepatitis B Virus Genetic Variation and TP53 R249S Mutation in Patients with Hepatocellular Carcinoma in Thailand

Chronic hepatitis B virus (HBV) infection and dietary exposure to aflatoxin B1 (AFB1) are major risk factorsfor hepatocellular carcinoma (HCC). The aim of this study was to evaluate the role of HBV genetic variationand the R249S mutation of the p53 gene, a marker of AFB1-induced HCC, in Thai patients chronically infectedwith HBV. Sixty-five patients with and 89 patients without HCC were included. Viral mutations and R249Smutation were characterized by direct sequencing and restriction fragment length polymorphism (RFLP)in serum samples, respectively. The prevalences of T1753C/A/G and A1762T/G1764A mutations in the basalcore promotor (BCP) region were significantly higher in the HCC group compared to the non-HCC group.R249S mutation was detected in 6.2% and 3.4% of the HCC and non-HCC groups, respectively, which was notsignificantly different. By multiple logistic regression analysis, the presence of A1762T/G1764A mutations wasindependently associated with the risk of HCC in Thai patients.     

Loss of heterozygosity at chromosome 13q in hepatocellular carcinoma: identification of three independent regions

Loss of heterozygosity (LOH) on chromosome 13q is one of the most common genetic alterations in hepatocellular carcinoma (HCC) and might be involved in liver cancer development through inactivation of tumour suppressor genes. In order to narrow down the region of 13q loss, we examined the pattern of loss of heterozygosity (LOH) in tumours from 88 HCC patients, using 18 microsatellite markers on 13q. Thirty-eight of the 88 tumours (43%) showed LOH for at least one marker. Of these, two tumours (5%) showed 13q whole arm allelic loss, while the remaining 36 tumours (95%) had partial allelic loss. The LOH pattern defined by the 36 tumours suggested the existence of at least three different smallest common deleted regions which might be involved in the carcinogenesis of HCC. The first, the most centromeric in the 13q12.3 is, close to the BRCA2 gene, defined by D13S171; the second, the most telomeric region in the 13q31-32 band, is defined by D13S154 and D13S157; the third, the intermediate region at 13q14.3, which is near the RB gene, is defined by loci D13S268. The rate of LOH at 13q31-32 was significantly higher in Hepatitis B-surface antigen (HBsAg)-positive patients than HBsAg-negative HCC patients, pointing to a candidate gene related to the development of HBsAg-positive HCCs.     

No evidence of replication error phenotype in primary gastric lymphoma of mucosa-associated lymphoid tissue

Replication error (RER) phenotype, caused by deficiency of DNA mismatch repair genes and revealed by widespread microsatellite instability, has been detected in subsets of a wide variety of solid tumors, but rarely in lymphomas in general. So far, the involvement of RER phenotype in the pathogenesis of gastric lymphoma of mucosa-associated lymphoid tissue (MALT) type has not been conclusively established. We therefore examined 9 microsatellite loci on 5 chromosomes [D2S123, D3S11, D3S1261, D3S1262, D3S1265, D6S262, D18S59, a CTTT(T) repeat in intron 20 of RB1 gene and a CA repeat in p53 locus] in 33 cases of primary gastric MALT lymphoma for evidence of microsatellite instability by polymerase chain reaction using primers end-labeled with [γ-³³P] ATP. Although novel-length allele was observed in 7 of 33 cases (21.2%), none of these 7 cases showed changes in more than one locus. RER phenotype was scored as positive in a case when more than 1 of the 9 examined microsatellite loci showed length alterations. Accordingly, none of the 33 cases had a RER phenotype. This result suggests that the pathogenesis of gastric MALT lymphoma does not involve RER phenotype. It is consistent with the general observations in lymphomas, but is highly in contrast to a previous report showing more than 50% of MALT lymphomas with the RER phenotype. Int. J. Cancer 76:635–638, 1998.© 1998 Wiley-Liss, Inc.     

Fluorescent-based BAT-26 analysis for distinct screening of microsatellite instability in colorectal cancers

For easy screening of genetic instability in colorectal cancers, we tried BAT-26 and BAT-25 mononucleotide repeats using fluorescent analysis and evaluated their usefulness and problems compared with other markers: D5S346, D17S250, D2S123, and D2S391, D4S392 (located near BAT-26 and BAT-25 respectively). The high-frequency of MSI (MSI-H) tumours, defined as tumours having instability in more than two markers, were detected in 8/146 (5.5%). These MSI-H cases were younger ages at diagnosis, and showed significantly higher incidences of right side location, and poorly differentiated histology than other cases (p<0.05). Four cases (2.7%) showed a 1 bp size shift in BAT-26 and 2 of them showed loss of heterozygosity (LOH) at D2S391 near BAT-26 locus. Among 9 cases with a 1 bp size shift in BAT-25, 6 cases showed LOH at D4S392 near the BAT-25 locus (p=0.035). In all 4 cases, non-cancerous DNA had two analogous peaks of BAT-26, indicating the heterozygosity of BAT-26 in constitutional DNA. This phenomenon was also detected in the peaks of BAT-25 in some cases, in whose constitutional DNAs, 1 bp size shift was also detectable in three other markers. To elucidate the reasons for the alterations of the 1 bp size shift of peak of these markers, we examined by microsatellite analysis mixed samples of tumour DNA with complete loss of the one allele at the 1p loci and each constitutional DNA sample of neuroblastoma patients. One base shift of the peak signal of the microsatellite marker was clearly obtained in proportion to the ratio of cancerous DNA and constitutional DNA. Fluorescent-based analysis of BAT-26 or BAT-25 was easy and useful for detection of MSI-H in colorectal cancers without analyzing non-cancerous DNA. A 1 bp size shift in BAT-26 or BAT-25 was considered to be affected by LOH at these loci. Thus, it is important to distinguish MSI from LOH to evaluated MSI using these markers.     

肝细胞癌8号染色体微卫星变异的研究(英文)

目的探讨肝细胞癌(HCC)8号染色体微卫星变异的特点及其与临床病理的相关性。方法采用 MegaBACE 500型自动化 DNA 分析系统,对56例 HCC 中8号染色体上10个微卫星的杂合性缺失(LOH)、微卫旱不稳定性(MSI)和等位基因失衡(AI)3种变异特征进行检测。结果 56例 HCC 在8号染色体上10个基因座发生 LOH 的总频率为66.1%(37/56),MSI 的频率为12.5%(7/56),AI 的频率为19.6%(11/56)。LOH 以 D8S261最高为53.5%(23/43),其次为 D8S1721(52.5%)和 D8S1771(52.5%)。D8S277基因座,血清HBsAg 阳性患者的 LOH 频率显著高于 HBsAg 阴性者(P<0.01),D8S261、D8S298和 D8S1733基因座,血清 HBsAg 阴性患者的 LOH频率显著高于 HBsAg 阳性者(P<0.01);D8S298和 D8S1771基因座.肿瘤直径>3cm 的 LOH 率明显高于≤3cm 组(P<0.05和 P<0.01);在 D8S1721基因座,无包膜或包膜不完整的肿瘤的 LOH 显著高于包膜完整的肿瘤(P<0.01);D8S298和 D8S1771基因座,肝内转移者的 LOH 明显高于无肝内转移者(P<0.05)。MSI 和 AI 与 HCC 临床病理学特点无明显相关性。结论 HCC 的8号染色体上存在广泛的微卫星变异,其中以代表肿瘤抑制基因路径的 LOH 方式在 HCC 的发生和发展过程中起重要作用,代表错配修复基因路径的 MSI 的作用次之。特定基因座的 LOH 与临床和病理学参数有一定的相关性。     

肝细胞癌8号染色体微卫星变异的研究

目的　　探讨肝细胞癌(HCC)8号染色体微卫星变异的特点及其与临床病理的相关性。方法采用MegaBACE　500型自动化DNA分析系统,对56例HCC中8号染色体上10个微卫星的杂合性缺失(LOH)、微卫星不稳定性(MSI)和等位基因失衡(AI)3种变异特征进行检测。结果　　56 例HCC 在8 号染色体上10 个基因座发生LOH 的总频率为66.1%(37 /56),MSI 的频率为12.5%(7 /56),AI的频率为19.6%(11/56)。LOH以D8S261最高为53.5%(23/43),其次为D8S1721(52.5%)和D8S1771(52.5%)。D8S277基因座,血清HBsAg阳性患者的LOH频率显著高于HBsAg阴性者(P<0.01),D8S261、D8S298和D8S1733基因座,血清HBsAg阴性患者的LOH频率显著高于HBsAg阳性者(P<0.01);D8S298和D8S1771基因座,肿瘤直径>3cm的LOH率明显高于￣<3cm组(P<0.05和P<0.01);在D8S1721基因座,无包膜或包膜不完整的肿瘤的LOH显著高于包膜完整的肿瘤(P<0.01);D8S298和D8S1771基因座,肝内转移者的LOH明显高于无肝内转移者(P<0.05)。MSI和AI与HCC临床病理学特点无明显相关性。结论　　HCC的8号染色体上存在广泛的微卫星变异,其中以代表肿瘤抑制基因路径的LOH方式在HCC的发生和发展过程中起重要作用,代表错配修复基因路径的MSI的作用次之。特定基因座的LOH与临床和病理学参数有一定的相关性。     

肝癌染色体17p13.3区的杂合性缺失分析及缺失区连续克隆群的构建

目的　检测原发性肝癌在染色体 17p13.3区的杂合性缺失状况 ,确定其共同缺失范围和最小热点缺失范围 ,并获得缺失范围内基因组克隆和构建连续克隆群。方法　应用Southern杂交分析VNTR(variablenumberoftandemrepeat,VNTR)和RFLP标志在肝癌中杂合性缺失 (LOH)状况。应用PCR扩增微卫星标志 ,变性聚丙烯酰胺凝胶电泳分析各个微卫星标志的LOH状况。以微卫星标志为引物 ,经过 3轮PCR筛选阳性基因组克隆。通过检测各位点标志对基因组克隆的反应 ,构建连续克隆群。结果　检测了 5 4份原发性肝癌样品在染色体 17p13.3区 16个位点标志和染色体 17p13.1区的p5 3基因的TP5 3位点标志的LOH情况 ,发现从D17S5位点至D17S34位点间的各个标志都有较高LOH ,频率 >6 3%。而从D17S5位点起、近着丝粒方向的 3个标志LOH率都较低或无LOH。染色体17p13.1的TP5 3标志只有 31%的LOH ,低于染色体 17p13.3区的D17S5至D17S34位点间各标志的LOH率。有 2例肝癌样品在近端粒的D17S34、D17S186 6位点和近着丝粒的D17S5、D17S15 74位点均无LOH ,但在D17S849至D17S15 74间的各位点上均呈LOH或为纯合子。在缺失范围内 ,共筛选了 18个位点的基因组克隆 ,获得了相对应的阳性基因组克隆 ,经过检测各位点对基因组克隆的反应性 ,构建了覆盖 9个标     

肝癌染色体17p13.3区的杂合性缺失分析及缺失区连续克隆群？…

目的 检测原发性肝癌在染色体１７ｐ１３．３区的杂合性缺失状况,确定其共同缺失范围和最小热点缺失范围,并获得缺失范围内基因组克隆和构建连续克隆群。方法 应用Ｓｏｕｔｈｅｍ杂交分析ＶＮＴＲ（ｖａｒｉａｂｌｅ ｎｕｍｂｅｒ ｏｆ ｔａｎｄｅｍ ｒｅｐｅａｔ,ＶＮＴＲ）和ＲＦＬＰ标志在肝癌中杂合性缺失（ＬＯＨ）状况。应用ＰＣＲ扩增微卫星标志,变性聚丙烯酰胺凝胶电泳分析各个微卫星标志的ＬＯＨ状况。以微卫星标     

肝外胆管癌染色体3p21.3区段微卫星不稳定和杂合性缺失分析

目的:研究肝外胆管癌染色体3p21.3区段的微卫星不稳定性(MSI)及杂合性缺失(LOH),探讨染色体3p21.3区段遗传不稳定性与肝外胆管癌的发生发展的关系,定位该区段上肝外胆管癌相关肿瘤基因。方法:用PCR-SSCP方法检测24例肝外胆管癌染色体3p21.3区段上D3S1568,D3S1621,D3S1578和D3S1289四个微卫星位点的MSI和LOH发生率,分析其与临床病理因素之间的关系。结果:24例肝外胆管癌组织中,四个微卫星位点的MSI和LOH平均发生率分别为7.23%和15.63%。其中D3S1621位点的LOH最高(45.83%,11/24),并与TNM分期、是否伴有局部/淋巴结转移相关(p<0.05)。结论:染色体3p21.3区段D3S1621位点高频率杂合性缺失,提示3p21.3区段可能定位有肝外胆管癌的候选抑癌基因,并在肝外胆管癌的发生发展过程中发挥重要作用。     

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.     

原发性肝癌8号和16号染色体杂合子丢失的研究

目的:分析人肝细胞肝癌(HCC)组织中染色体8和16部分染色体片段的杂合子丢失及与临床病理关系,初步筛选HCC相关的抑癌基因,为HCC的早期诊断、预后预警提供可能的新分子标记物.方法:应用聚合酶链反应-变性聚丙烯酰胺凝胶-银染法分析45例HCC组织标本中分别位于染色体8和16上的具有高度多态性微卫星位点的杂合性丢失(LOH)状态.结果:发生LOH的总频率为68.89％ (31/45),其中D16S511位点的LOH发生率最高为53.33％ (24/45),其次是D8S261( 39.02％,16/41)和D8S499(34.88％,15/43).结论:染色体16q23、8p22-21.3及8p12区域的LOH发生频率高,可能存在与HCC发生发展相关的新的抑癌基因,特定位点的遗传变异可能与HBV感染、临床病理恶性程度等预后因素相关.