食管癌APC/MCC、DCC基因杂合丢失的研究

目的研究ＡＰＣ（ａｄｅｎｏｍａｔｏｕｓｐｏｌｙｐｏｓｉｓｃｏｌｉ）、ＭＣＣ（ｍｕｔａｔｉｏｎｉｎｃｏｌｏｒｅｃｔａｌｃａｎｃｅｒ）和ＤＣＣ（ｄｅｌｅｔｅｄｉｎｃｏｌｏｒｅｃｔａｌｃａｎｃｒ）基因在人食管癌组织中的变化。方法采用聚合酶链反应（ＰＣＲ）及限制性片段长度多态现象（ＲＦＬＰ）法检测了４６例食管癌组织中ＡＰＣ、ＭＣＣ和ＤＣＣ基因的杂合缺失。结果ＡＰＣ、ＭＣＣ和ＤＣＣ位点的杂合性丢失的发生频率分别为２９．０％（９／３１）、３３．３％（８／２４）和３２．４％（１２／３７）。然而,这些基因位点的杂合性丢失与肿瘤病理学类型、肿瘤的大小、浸润性及转移性无统计学的显著相关性（Ｐ＞０．０５）。结论ＡＰＣ、ＭＣＣ和ＤＣＣ基因位点的杂合性丢失在一定程度上是食管癌基因改变的普遍现象,并可能在肿瘤的发生中起作用。     

结直肠癌APC基因的PCR—SSCP检测研究进展

结直肠癌ＡＰＣ基因的ＰＣＲ－ＳＳＣＰ检测研究进展许洪卫关键词肿瘤抑制基因基因突变聚合酶链式反应大肠肿瘤中图号Ｒ７３５．３４结直肠癌（ｃｏｌｏｒｅｃｔａｌｃａｎｃｅｒ，ＣＲＣ）等肿瘤发生发展的分子生物学机理研究，近几年随着分子生物学技术的提高而深入。目...     

关于鼻咽癌TNM临床分期的修改建议

关于鼻咽癌ＴＮＭ临床分期的修改建议胡心传ＰＲＯＰＯＳＡＬＯＮＭＯＤＩＦＩＥＤＴＮＭＳＴＡＧＩＮＧＳＹＳＴＥＭＦＯＲＮＡＳＯＰＨＡＲＹＮＧＥＡＬＣＡＲＣＩＯＮＭＡ（ＮＰＣ）￥ＨｕＸｉｎ－ｃｈｕａｎ（ＨｕｂｅｉＰｒｏｖｉｎｃｉａｌＣａｎｃｅｒＨｏｓｐｉｔ...     

LRP,MRP,MDR1基因在非小细胞肺癌中的表达及其临床意义

目的 探讨肺耐药蛋白（ｌｕｎｇ ｒｅｓｉｓｔａｎｃｅ ｐｒｏｔｅｉｎ,ＬＲＰ）,多药耐药蛋白（ｍｕｌｔｉｄｒｕｇ ｒｅｓｉｓｔａｎｃｅａｓｓｏｃｉａｔｅｄ ｐｒｏｔｅｉｎ,ＭＲＰ）,和多药耐药基因（ｍｕｌｔｉｄｒｕｇ ｒｅｓｉｓｔａｎｅ,ＭＤＲ１）ｍＲＮＡ在非小细胞肺癌（ｎｏｎ－ｓｍａｌｌ ｃｅｌｌ ｃａｎｃｅｒ,ＮＳＣＬＣ）中的共表达及临床意义。方法 ＲＴ－ＰＣＲ检测ＮＳＣＬＣ冰冻组织中上述耐药     

A STUDY OF THE TNM STAGING SYSTEM FOR NASOPHARYNGEAL CARCINOMA (NPC)

ＡＳＴＵＤＹＯＦＴＨＥＴＮＭＳＴＡＧＩＮＧＳＹＳＴＥＭＦＯＲＮＡＳＯＰＨＡＲＹＮＧＥＡＬＣＡＲＣＩＮＯＭＡ（ＮＰＣ）ＬｉＣｈａｎｇｑｉｎｇ；李长青ＬｉａｏＬｉｎｇｘｉａ；廖玲霞（ＨｕｂｅｉＣａｎｃｅｒＨｏｓｐｉｔａｌ，Ｗｕｈａｎ，４３００７０）Ａｂｓ...     

遗传性非息肉病性大肠癌(附100例大肠癌病例临床分析)

遗传性非息肉病性大肠癌（ＨｅｒｅｄｉｔａｒｙＮｏｎ－ｐｏｌｙｐｏｓｉｓＣｏｌｏｒｅｃｔａｌＣａｎｃｅｒ简称ＨＮＰＣＣ）被发现至今已１００余年，起初称为癌症家庭综合症，后经Ｌｙｎｃｈ系统总结，日益引起人们的广泛注意，故一般又称Ｌｙｎｃｈ综合症。本病的诊...     

ADVANCES IN PRIMARY LIVER CANCER RESEARCH

ＡＤＶＡＮＣＥＳＩＮＰＲＩＭＡＲＹＬＩＶＥＲＣＡＮＣＥＲＲＥＳＥＡＲＣＨＰｒｉｍａｒｙｌｉｖｅｒｃａｎｃｅｒ（ＰＬＣ）ｉｓａｒｅｌａｔｉｖｅｌｙｒａｒｅｍａｌｉｇｎａｎｃｙｉｎｔｈｅＷｅｓｔｅｒｎｗｏｒｌｄ，ｂｕｔｏｎｅｏｆｔｈｅｍｏｓｔｆｒｅｑｕｅ...     

ｄｄＰＣＲ与 ＡＲＭＳ-ＰＣＲ检 测 ＮＳＣＬＣ患者ＥＧＦＲ基因Ｔ７９０Ｍ突变的比较研究

目的：通过对比微滴式数字 ＰＣＲ（ｄｒｏｐｌｅｔｄｉｇｉｔａｌＰＣＲ,ｄｄＰＣＲ）和突变扩增阻滞系统 ＰＣＲ（ａｍｐｌｉｆｉｃａｔｉｏｎｒｅｆｒａｃ ｔｏｒｙｍｕｔａｔｉｏｎｓｙｓｔｅｍＰＣＲ,ＡＲＭＳ ＰＣＲ）检测非小细胞肺癌（ｎｏｎ ｓｍａｌｌｃｅｌｌｌｕｎｇｃａｎｃｅｒ,ＮＳＣＬＣ）表皮生长因子受体（ｅｐｉ ｄｅｒｍａｌｇｒｏｗｔｈｆａｃｔｏｒｒｅｃｅｐｔｏｒ,ＥＧＦＲ）基因 Ｔ７９０Ｍ突变的检测效能,综合分析两种检测方法的优势及适用范围。方法： 回顾性收集 １１５例 ＮＳＣＬＣ患者的标本,同时使用 ｄｄＰＣＲ和 ＡＲＭＳ ＰＣＲ两种方法检测 ＥＧＦＲ基因 Ｔ７９０Ｍ突变状态, 比较两种方法的检测结果,并分析不同样本类型对 ｄｄＰＣＲ检测结果的影响。结果：ｄｄＰＣＲ检测 Ｔ７９０Ｍ阳性率为 ６５．２％,ＡＲＭＳ ＰＣＲ阳性率为 ２７．８％,ｄｄＰＣＲ检测敏感性显著高于 ＡＲＭＳ ＰＣＲ（Ｐ＜０．０５）,两种方法检测一致率为 ６２．６％。ｄｄＰＣＲ＋ＡＲＭＳ－样本的 Ｔ７９０Ｍ平均阳性微滴数和平均突变丰度（１１,０．３５％）均显著低于 ｄｄＰＣＲ＋ＡＲＭＳ ＋样本（６３２．３,１７．７％）。ｄｄＰＣＲ检测基因组 ＤＮＡ和外周血游离 ＤＮＡ阳性率分别为 ５５．９％和 ７８．７％,不同样本类 型 Ｔ７９０Ｍ突变阳性微滴数和突变丰度无显著差别。结论：ｄｄＰＣＲ和 ＡＲＭＳ ＰＣＲ均可用于 ＮＳＣＬＣ患者 ＥＧＦＲ基因 Ｔ７９０Ｍ突变检测,二者具有良好的一致性,ｄｄＰＣＲ具有更高的灵敏性,在检测突变丰度较低的样本方面具有优势。     

食管癌组织中抑癌基因APC,MCC突变的研究

应用聚合酶链反应（ＰＣＲ）扩增与直接测序方法，分析抑癌基因ＡＰＣ、ＭＣＣ在食管癌中的变化，应用ＰＣＲ扩增，发现１／１０的食管癌组织有ＡＰＣ基因第１１外显子缺失，１／１０的食管癌组织有ＭＣＣ基因第１２外显子缺失，并发现１例食管癌旁癌组织有ＭＣＣ基因基因第１２个外显子缺失。ＰＣＲ直接测序发现：２／１０的食管癌标本有ＡＰＣ基因第１１外显子突变，２／７的食管癌组织有ＭＣＣ基因第１２外显子突变。以上研究证实     

A CASE REPORT OF PRIMARY CARDIAC RHABDOMYOSARCOMA

ＡＣＡＳＥＲＥＰＯＲＴＯＦＰＲＩＭＡＲＹＣＡＲＤＩＡＣＲＨＡＢＤＯＭＹＯＳＡＲＣＯＭＡＺｈａｎｇＺｈｅｎｈｕａ张珍华；ＣｈｅｎＲｅｎ陈韧；（ＴｈｅＦｉｒｓｔＴｅａｃｈｉｎｇＨｏｓｐｉｔａｌ，Ｘｉ’ａｎＭｅｄｉｃａｌＵｎｉｖｅｒｓｉｔｙ，Ｘｉ’ａｎ７１...     

Primary Gastric Carcinoma Cells Frequently Lose Heterozygosity at the APC and MCC Genetic Loci

Loss of heterozygosity (LOH) at APC and MCC gene loci (both mapped to 5q21) was investigated in 24 surgical specimens of primary gastric carcinomas using the polymerase chain reaction after tumor cell enrichment by cell sorting based on differences in DNA content. LOH at APC and/or MCC was detected in 87% (13/15) of the cases; at the APC in 86% (12/14) and at the MCC locus in 100% (7/7). LOH at the APC locus was always accompanied by LOH at the MCC locus. LOH at the APC and/or MCC was found in both differentiated and undifferentiated types in both early and advanced stages of gastric carcinoma. Thus, LOH at APC and/or MCC is considered to be one of the most prevalent genetic alterations in human gastric carcinoma and occurs at an early stage of the carcinogenesis.     

Allele loss from 5q21 (APC/MCC) and 18q21 (DCC) and DCC mRNA expression in breast cancer.

Thirty-four primary, untreated sporadic breast cancers were examined for loss of heterozygosity (LOH) at tumour suppressor loci involved in colorectal cancer: APC/MCC at 5q21 and DCC at 18q21. LOH was identified in 28% informative patients at 5q21 and 31% at 18q21. LOH at 5q21 and 18q21 was compared with allele loss at 17p13 and concurrent LOH at two or more of the loci was noted in 24% of tumours. Expression of a 12 kb DCC mRNA was demonstrated in 14/34 (42%) of the cancers and in all five tumours with LOH at the DCC locus there was an additional 11 kb DCC mRNA. Abnormalities of three loci involved in colorectal cancer (5q21, 17p13 and 18q21) therefore also occur in sporadic breast cancer. The accumulation of such genetic abnormalities may confer a growth advantage important in the development of breast cancer.     

显微切割法对肝细胞癌抑癌基因杂合性缺失的研究

目的 通过对肝细胞癌（HCC）抑癌基因（tumor suppressor genes,TSGs)杂合性缺失（loss of heterozygosity,LOH)谱系特点的分析，进一步了解HCC发生过程中多基因变异的特点。方法 采用显微组织切割法从石蜡包埋的组织切片中提取基因组DNA直接测序，对33例信息性HCC进行了6种TSGs(APC、DCC、MCC、OGC1、p53和RBI1）的LOH检测。结果 LOH的总体发生率为36.4％,其中p53:80.0%、OGG1：50.0%、APC：41.7%、RB1:20.0%、DCC:0.0%、MCC:0.0%。结论 在HCC的发生和发展过程中有多基因变异的参与，其中p53、OGG1和APC基因在HCC的发生中起重要作用，RB1的作用次之，而DCC和MCC基因的作用可能较小。     

Loss of heterozygosity of the Mutated in Colorectal Cancer gene is not associated with promoter methylation in non-small cell lung cancer

'Mutated in Colorectal Cancer' (MCC) is emerging as a multifunctional protein that affects several cellular processes and pathways. Although the MCC gene is rarely mutated in colorectal cancer, it is frequently silenced through promoter methylation. Previous studies have reported loss of heterozygosity (LOH) of the closely linked MCC and APC loci in both colorectal and lung cancers. APC promoter methylation is a marker of poor survival in non-small cell lung cancer (NSCLC). However, MCC methylation has not been previously studied in lung cancer. Therefore, we wanted to determine if MCC is silenced through promoter methylation in lung cancer and whether this methylation is associated with LOH of the MCC locus or methylation of the APC gene. Three polymorphic markers for the APC/MCC locus were analysed for LOH in 64 NSCLC specimens and matching normal tissues. Promoter methylation of both genes was determined using methylation specific PCR in primary tumours. LOH of the three markers was found in 41-49% of the specimens. LOH within the MCC locus was less common in adenocarcinoma (ADC) (29%) than in squamous cell carcinoma (SCC) (72%; P=0.006) or large cell carcinoma (LCC) (75%; P=0.014). However, this LOH was not accompanied by MCC promoter methylation, which was found in only two cancers (3%). In contrast, 39% of the specimens showed APC methylation, which was more common in ADC (58%) than in SCC (13%). Western blotting revealed that MCC was expressed in a subset of lung tissue specimens but there was marked variation between patients rather than between cancer and matching non-cancer tissue specimens. In conclusion, we have shown that promoter methylation of the APC gene does not extend to the neighbouring MCC gene in lung cancer, but LOH is found at both loci. The variable levels of MCC expression were not associated with promoter methylation and may be regulated through other cellular mechanisms.     

Loss of heterozygosity involves multiple tumor suppressor genes in human esophageal cancers.

Loss of heterozygosity occurring on various chromosomes has been described in the majority of human tumors. The targets of frequent or consistent subchromosomal deletions are believed to be tumor suppressor genes. We examined 72 esophageal tumors (46 squamous cell carcinomas and 26 adenocarcinomas) for loss of heterozygosity at the p53, Rb, APC, MCC, and DCC loci. Inclusion of these tumor suppressor genes in the allelic deletions was directly ascertained by performing polymerase chain reaction at polymorphic sites within the genes. Loss of heterozygosity occurred in 55% of informative cases at p53, in 48% of informative cases at Rb, in 66% at APC, in 63% at MCC, and in 24% at DCC. Ninety-three % of tumors informative at all loci (fully informative) lost heterozygosity of at least one locus. A high percentage of fully informative tumors (71%) also lost heterozygosity at more than one locus. There were no significant differences among histological types in the prevalence of loss of heterozygosity at any locus. There were correlations of losses involving MCC versus DCC, Rb, and p53. These data suggest that (a) allelic deletions including these tumor suppressor genes are important in the formation and/or progression of most esophageal cancers; (b) allelic deletions involving MCC may not occur independently of deletions involving other tumor suppressor genes; and (c) the accumulation of multiple allelic deletions involving specific tumor suppressor genes may be important in most esophageal tumorigenesis or tumor evolution.     

High-frequency of loss of expression and allelic deletion of the apc and mcc genes in human prostate-cancer

Loss of heterozygosity (LOH) or allelic deletion at various loci has been reported in the majority of human tumors. The frequently deleted targets are believed to be tumor suppressor genes. Recent studies have identified the APC and MCC genes at 5q21, as putative tumor suppressor genes. The APC and MCC genes have been implicated in the development of familial adenomatous polyposis coli and cancers of the gastrointestinal tract, ovary, breast and lung. In the present study, we investigated a possible role of the APC and MCC genes in prostate cancer development. mRNA expression of the APC and MCC genes and LOH at the APC and MCC loci were determined in prostate cancer tissues from 28 patients and 5 human prostatic adenocarcinoma cell lines. Of the informative cases, the frequency of LOH at the APC and MCC loci was 63% (10/16) and 54% (7/13), respectively. Overall, 65% (15/23) of the informative cases showed LOH at the APC and/or MCC gene. All prostate cancer cell lines showed homozygosity at all APC and MCC polymorphic sites studied. Approximately half (57%) of the tumor tissues examined showed a decreased expression of APC and MCC mRNA. Our data suggest that the APC and MCC genes may be involved in the formation of human prostate cancer (HPC).     

Genetic alterations in ulcerative colitis-associated neoplasia focusing on APC, K-ras gene and microsatellite instability.

The status of genetic alterations in ulcerative colitis (UC)-associated neoplasia (UCAN) was investigated focusing on microsatellite instability (MSI) which is seen in a certain fraction of colorectal carcinomas, and adenomatous polyposis coli (APC) gene and K-ras gene, in which mutations occur in the early stage of sporadic colorectal tumorigenesis. Thirty-one UCAN from 15 UC patients who had undergone colorectal resection at our institution were investigated. There were 8 lesions of invasive carcinoma, 15 high-grade dysplasia (HGD) and 8 low-grade dysplasia (LGD). DNA was extracted from each neoplastic lesion and corresponding non-neoplastic tissue by a microdissection method. MSI status at 9 microsatellite loci, loss of heterozygosity (LOH) at the APC locus, and K-ras codon 12 point mutation were examined. As for MSI, 4/31 (13%) UCAN (carcinoma: 1/8 (13%), HGD: 2/15 (13%), LGD: 1/8 (13%)) were MSI-high (3 or more unstable loci) and 12/31 (39%) UCAN (carcinoma: 3/8 (38%), HGD: 6/15 (40%), LGD: 3/8 (38%)) were MSI-low (1 or 2 unstable loci). LOH at the APC locus was not found in 9 UCAN from 6 informative (heterozygous) cases. The K-ras mutation rate of UCAN was 3/31 (9.7%) (carcinoma: 2/8 (25%), HGD: 1/15 (7%) and LGD: 0/8). MSI is relatively common in UCAN and is present at the early stage of tumorigenesis of UCAN, while the involvement of genetic alterations of the APC gene and K-ras gene is small. MSI may be one of the mechanisms of the increased neoplastic risk in UC, and UCAN may develop through a different carcinogenic pathway from sporadic carcinomas.     

Genetic Alterations in Ulcerative Colitis-associated Neoplasia Focusing on APC, K-ras Gene and Microsatellite Instability

The status of genetic alterations in ulcerative colitis (UC)-associated neoplasia (UCAN) was investigated focusing on microsatellite instability (MSI) which is seen in a certain fraction of colorectal carcinomas, and adenomatous polyposis coli (APC) gene and K-ras gene, in which mutations occur in the early stage of sporadic colorectal tumorigenesis. Thirty-one UCAN from 15 UC patients who had undergone colorectal resection at our institution were investigated. There were 8 lesions of invasive carcinoma, 15 high-grade dysplasia (HGD) and 8 low-grade dysplasia (LGD). DNA was extracted from each neoplastic lesion and corresponding non-neoplastic tissue by a microdissection method. MSI status at 9 microsatellite loci, loss of heterozygosity (LOH) at the APC locus, and K-ras codon 12 point mutation were examined. As for MSI, 4/31 (13%) UCAN (carcinoma: 1/8 (13%), HGD: 2/15 (13%), LGD: 1/8 (13%)) were MSI-high (3 or more unstable loci) and 12/31 (39%) UCAN (carcinoma: 3/8 (38%), HGD: 6/15 (40%), LGD: 3/8 (38%)) were MSI-low (1 or 2 unstable loci). LOH at the APC locus was not found in 9 UCAN from 6 informative (heterozygous) cases. The K-ras mutation rate of UCAN was 3/31 (9.7%) (carcinoma: 2/8 (25%), HGD: 1/15 (7%) and LGD: 0/8). MSI is relatively common in UCAN and is present at the early stage of tumorigenesis of UCAN, while the involvement of genetic alterations of the APC gene and K-ras gene is small. MSI may be one of the mechanisms of the increased neoplastic risk in UC, and UCAN may develop through a different carcinogenic pathway from sporadic carcinomas.     

Allelic losses associated with the metastatic potential of colorectal-carcinoma

The aim of this study was to define the association of allelic losses with the metastatic potential of colorectal carcinoma and to determine whether allelic losses can be genetic markers for the prognosis of patients with colorectal carcinoma. Eighty primary colorectal tumors and 31 liver metastases from 95 patients were examined for loss of heterozygosity (LOH) at the APC, p53, RB, DCC and chromosome 14q loci by using polymerase chain reaction-single strand conformation polymorphism analysis and restriction fragment length polymorphism analysis. The incidence of LOH at the DCC and RB loci and on chromosome 14q in liver metastases was significantly higher than that in primary tumors. DCC and RB alterations were detected more frequently in primary tumors with higher metastatic potential. Although no statistically significant association was found between these losses and survival or distant metastasis, patients with DCC losses showed poorer survival by multivariate analysis (p=0.056). Thus, inactivation of the DCC and RB genes and gene(s) on chromosome 14q seem to be critical genetic events for the acquisition of metastatic potential in colorectal carcinoma. However, further studies will be required to utilize these genetic alterations as valuable prognostic markers.