结直肠癌非随机性染色性异常的研究

对１８例结直肠癌患者采用实体瘤短期体外悬浮细胞增减法进行染色体分析。结果：染色体结构重排涉及１７ｐ、５ｑ、６ｑ（７８％、６１％、５０％），染色体增加频率最高的是７号、３号（７２％、６６％），丢失则最常见于１７号、５号、１８号（５０％、４４％、３３％）。大量标记染色体、双微体及超倍体核型预示肿瘤易早期复发和转移。此结果提示：１７号、５号及１８号染色体畸变与结直肠癌发生发展有密切关系。非随机性染色体异     

睾丸肿瘤染色体杂合性丢失及微卫星不稳定性研究

目的　探讨睾丸肿瘤的发生、发展与微卫星不稳定性（ ＭＳＩ） 及染色体杂合性丢失（ＬＯＨ）的关系。　方法　利用ＰＣＲＭＩＡ技术,选用８ 种微卫星标记位点,分析２２ 例睾丸肿瘤ＬＯＨ及ＭＳＩ的变化。　结果　２２ 例中１４ 例出现ＬＯＨ（６４％ ）。定位于第９ 号染色体上的Ｄ９Ｓ６３ 位点的ＬＯＨ 发生率最高为４５％ ,次为第５ 号染色体上的ＡＰＣ位点（４３ ％） 及第１８ 号染色体上的ＤＣＣ位点（２５ ％） ;８ 例表现为ＭＳＩ（３６ ％） ,１７ 例表现为ＬＯＨ 或（ 和）ＭＳＩ,总阳性率为７７％ 。　结论　染色体９ｑ 及５ｑ 上存在的抑癌基因的失活以及微卫星不稳定性改变可能在睾丸肿瘤的发生发展中起重要作用。     

睾丸生殖细胞肿瘤12号染色体畸变及其临床意义

采用染色体Ｇ带的分析方法对３５例睾丸生殖细胞肿瘤进行了研究，初级细胞培养获得１０例异常核型。为观察，分析１２号染色体的畸变形式，将与１２号染色体畸变有关的核型及其临床资料进行比较，分析。结果表明，该染色体的畸变形式有：＋１２（７０％），ｉ（１２ｐ）（７０％），１２ｑ＾＋（５０％），１２ｑ＾－（２０％）。其中，非精原细胞瘤的＋１２，ｉ（１２ｐ）发生率明显高于精原细胞瘤（Ｐ＜０．０５，＜０．０１）。结     

结直肠癌合并腺瘤的处理

结直肠癌合并腺瘤者极为常见，临床上往往重视结直肠癌而忽视或遗漏了对腺瘤的处理，是影响结直肠癌术后疗效及结直肠重复癌发生率高的重要因素之一。我院１９９５年１月至２０００年１２月期间共收治结直肠癌合并腺瘤患者１３２例，占同期结直肠癌的１８％，分析如下。临床资料本组患者男７５例、女５７例，平均年龄６２岁。腺瘤分布于直肠５７例（４３．２％），乙状结肠２４例（１８．２％），其它部位５１例（３８．６％）。腺瘤单发７２例（５４．５％），多发６０例（４５．５％）。腺瘤直径小于１．０cm８０例（６０．６％），１～２…     

散发性结直肠癌患者18号染色体高频杂合缺失的研究

目的：探讨散发性结直肠癌患者18号染色体上抑癌基因相关的杂合缺失（LOH）情况，并探索新的抑癌基因位点。方法：对83例散发性结直肠癌患者基因组DNA用14个不同荧光标记的高度多态性微卫生引物，扩增相应的微卫星位点，平均距离为10厘摩（centi-morgan,cM）。用ABI PRISM377测序仪进行基因扫描，统计各位点杂合缺失率。结果：在12个获得有效数据的微卫星位点中，平均杂合缺失率为36．78％,18p中最高为D18S53（38．09％），18q中最高为D18S474（55．74％）。4位患者的18号染色体所有杂合位点都存在缺失，30位患者的杂合缺失位点不少于50％（平均6个／人）；缺失位点少于50％的有53人（平均1个／人）。结论：结直肠癌患者18号染色体存在高频的LOH，并以整体缺失为特点。存在高频LOH的区域定位有转化生长因子（TGF）信号传导相关基因、结直肠癌缺失基因（DCC）、Rb结合蛋白8(RbBP8），特别是TGF信号传导相关基因MADH2、4、转化生长因子－β1反应元件（TGF－β1）等的缺失可能对结直肠癌的发生有重要影响。18p也有存在未知抑癌基因的可能。     

131Ⅰ标记单克隆抗体CL3瘤内注射对荷人结肠癌裸鼠的放射免疫治疗

我们采用１３１Ⅰ标记单克隆抗体ＣＬ３瘤内注射治疗荷人结肠癌裸鼠移植瘤，与腹腔注射比较：大剂量组每鼠给药１８．５ＭＢｑ，观察３４天，１６天后前者的肿瘤生长抑制率高于后者，分别为５７．９％±１０．２％和４７．２％±１６．６％（Ｐ＜０．０５），肿瘤完全抑制率分别为６／１６和１／８；小剂量组每例５．３６ＭＢｑ，观察１７天，６天后，前者的肿瘤生长抑制率明显高于后者，分别为４９．６％±１７．５％和２６．１％±３．４％（Ｐ＜０．０１）．计算小剂量给药后五天的肿瘤累积吸收剂量，瘤内注射是腹腔注射组的３．３倍，分别为１８．７Ｇｙ和５．７Ｇｙ．结果提示在肿瘤放射免疫治疗中采用瘤内注射法给药，具有低毒高效的治疗作用，临床实用价值较高。     

多原发大肠癌67例临床分析

目的　探讨多原发大肠癌发病率、病理及临床特点、诊断及治疗方法。 方法　对６７ 例多原发大肠癌患者的临床资料进行回顾性分析。 结果　６００ 例结直肠癌中，有同时多原发癌４７ 例（７８ ％ ） ，异时多原发癌２０ 例（３３ ％ ） 。多原癌伴息肉者３１ 例（４６ ％ ） ，其中１７ 例为息肉癌变（１２ ％ ） ，本组手术根治切除５４ 例，姑息切除５ 例，造口５ 例，仅探查者３ 例。术后１０ 年生存率６２ ％ ，８ 年生存率７３ ％ ，５ 年生存率６７ ％ 。 结论　利用纤结镜作术前、后检查，术中注意仔细探查，是提高本病发现率的重要手段；首次手术彻底切除癌与癌前病变是提高术后生存率的重要因素。     

结直肠癌肝转移危险因素分析

近年,随着肿瘤生物学和外科技术进步,外科治疗结直肠癌肝转移已明显提高了生存率［１］。本文对近５年作者收治的经病理证实的４１例结直肠癌肝转移危险因素进行回顾性分析,对结直肠癌肝转移的病理特点和进一步提高肝转移早期诊断、早期治疗水平作一探讨。１　临床资料本组男３１例,女１０例,男女之比为３．１∶１。年龄平均５５岁（３３～７３岁）。发生部位：２４例（５８．５％）位于乙状结肠,１０例（２４．４％）位于直肠,位于结肠其它部位者７例（１７．１％）。无病间期〔结直肠癌手术至Ｂ超和（或）ＣＴ发现肝内转移病灶时间…     

^131I标记单克隆抗体CL3瘤内注射对荷人结肠癌裸鼠的放射…

我们采用＾１３１Ｉ标记单克隆抗体ＣＬ３瘤内注射治疗荷人结肠癌裸鼠移植瘤，与腹腔注射比较：大剂量组每鼠给药１８．５ＭＢｑ，观察３４天，１６天后前者的肿瘤生长抑制率高于手者，分别为５７．９％±１０．２％和４７．２％±１６．６％（Ｐ＜０．０５），肿瘤完全抑制率分别为６／１６和１／８；小剂量组每例５．３６ＭＢｑ观察１７天，６天后，前者的肿瘤生长抑制率明显高于后者，分别为４９．６％±１７．５％和２６．１％±     

结直肠癌发病风险与性激素间的关系

有文献报道，性激素可以影响结直肠癌的发生和发展。但是，尚未见有文献报道内源性的性激素水平与结直肠癌发病风险的关系。本研究通过健康研究中心机构，收集730名女性（293例结直肠癌患者及437名正常人）和1158名男性（439例结直肠癌患者及719名正常人）的相关资料，包括生活方式、病史、饮食及血样，检测其血浆中的雌激素酮、雌二醇、睾酮和性激素结合球蛋白及c-肽水平。结果显示，男性当中的总睾酮（95％CI：0．40～0．96）、性激素结合球蛋白（95％CI：0．42～0．99）及雌二醇／睾酮水平（95％CI：1．58～4．36）是发生结直肠癌的危险因素（P〈O．05）。在女性当中，雌二醇／睾酮水平（95％CI：0．22～0．84）是发生结直肠癌的危险因素。     

比较基因组杂交研究原发性胃癌的遗传学变异

目的研究原发性胃癌发生、发展过程中遗传学变异情况。方法采用比较基因组杂交分析23例原发性胃癌基因组DNA拷贝数变化情况。结果原发性胃癌患者平均每例肿瘤染色体臂变化数为7.52,扩增数要明显多于丢失数(5.38∶2.14)。DNA拷贝数扩增常见于8q(9/21,42.9%)、20q(9/21,42.9%)、17q(8/21,38.1%)、3q(7/21,33.3%)、7q(7/21,33.3%)、11q(6/21,28.6%)、13q(6/21,28.6%)、1q(5/21,23.8%)、20p(5/21,23.8%);DNA拷贝数缺失常见于17p(7/21,33.3%)、18q(6/21,28.6%)、5q(5/21,23.8%)、8p(5/21,23.8%)、9p(5/21,23.8%)。结论原发性胃癌中存在多条染色体拷贝数的变化,由此引起相应癌基因的扩增和抑癌基因的丢失可能参与了胃癌的发生和发展。     

Genetic aberrations in primary cutaneous large B-cell lymphoma: a fluorescence in situ hybridization study of 25 cases

In contrast to nodal large B-cell lymphomas, recurrent chromosomal aberrations have been studied only in a small number of cases of primary cutaneous diffuse large B-cell lymphoma (PCDLBCL). We investigated 25 PCDLBCLs (classified according to the WHO-EORTC classification into PCDLBCL, leg-type, 8; and PCDLBCL, other, 17), using an interphase fluorescence in situ hybridization technique. All cases were analyzed for chromosomal aberrations commonly observed in nodal large B-cell lymphomas, including structural aberrations of the genes BCL2, BCL6, and c-MYC, and numerical aberrations of the chromosomes/genes 3, 7, 8, 11, 12, 13, 17, 18q, RB1, and p53. We observed genetic aberrations in 19 (76%) of 25 patients. The most frequent numerical aberrations were gains of chromosome 12 (7 of 25, 28%), 7 (5 of 25, 20%), 3 (5 of 25, 20%), 18q (3 of 25, 12%), 11 (3 of 25, 12%), X (3 of 25, 12%), and losses of chromosome/gene 17/p53 (3 of 25, 12%). BCL2, c-MYC, and BCL6 were rearranged with the IGH gene in 4 (16%), 1 (4%), and none (0%) of 25 cases, respectively. Most aberrations were homogeneously distributed among cases of PCDLBCL, leg-type and of PCDLBCL, other, cases located on the leg or at other body sites, cases with round and cleaved cell morphology, and Bcl-2+ and Bcl-2- cases. These results suggest that PCDLBCLs show similar chromosomal aberrations irrespective of classification, anatomic site, cell morphology, and Bcl-2 expression, and that many similarities between primary cutaneous and nodal diffuse large B-cell lymphomas can be observed.     

Molecular cytogenetic analysis of medulloblastomas and supratentorial primitive neuroectodermal tumors by using conventional banding, comparative genomic hybridization, and spectral karyotyping

OBJECT: Medulloblastomas and related primitive neuroectodermal tumors (PNETs) of the central nervous system are malignant, invasive embryonal tumors with predominantly neuronal differentiation that comprise 20% of pediatric brain tumors. Cytogenetic analysis has shown that alterations in chromosome 17, particularly the loss of 17p and the formation of isochromosome 17q, as well as the gain of chromosome 7 are the most common changes among this group of tumors. Comparative genomic hybridization (CGH) studies have largely confirmed these cytogenetic findings and have also identified novel regions of gain, loss, and amplification. The advent of more sophisticated multicolored fluorescence in situ hybridization (FISH) procedures such as spectral karyotyping (SKY) now permits complete recognition of all aberrations including extremely complex rearrangements. The authors report a retrospective analysis of 19 medulloblastoma and five PNET cases studied using combinations of classic banding analysis, FISH, CGH, and SKY to examine comprehensively the chromosomal aberrations present in this tumor group and to attempt to identify common structural rearrangement(s). METHODS: The CGH data demonstrate gains of chromosomes 17q and 7 in 60% of the tumors studied, which confirms data reported in the current literature. However, the authors have also combined the results of all three molecular cytogenetic assays (Giemsa banding, CGH, and SKY) to reveal the frequency of chromosomal rearrangement (gained, lost, or involved in structural rearrangement). CONCLUSIONS: The combined results indicate that chromosomes 7 and 17 are the most frequently rearranged chromosomes (10.1% and 8.9%, respectively, in all rearrangements detected). Furthermore, chromosomes 3 (7.8%), 14 (7%), 10 (6.7%), and 22 (6.5%) were also found to be frequently rearranged, followed by chromosomes 6 (6.5%), 13 (6.2%), and 18 (6.2%). Eight (33%) of 24 tumors exhibited high-level gains or gene amplification. Amplification of MYCN was identified in four tumors, whereas amplification of MYCC was identified in one tumor. One tumor exhibited a high-level gain of chromosome 9p. Additionally, desmoplastic medulloblastomas and large-cell medulloblastomas exhibited higher karyotype heterogeneity, amplification, and aneusomy than classic medulloblastomas.     

Chromosomal changes in incidental prostatic carcinomas detected by comparative genomic hybridization

OBJECTIVES: The genetic changes underlying the development and progression of prostate cancer are poorly understood. To identify chromosomal regions in incidental prostatic carcinoma (T1a and T1b) was the primary aim of this study. MATERIALS AND METHODS: We used comparative genomic hybridization (CGH) to search for DNA sequence copy number changes on a series of 48 T1 prostate cancer diagnosed by transurethral resection (TURP) and by adenomectomy. Incidental prostatic carcinomas have not been studied by CGH previously. RESULTS: CGH analysis indicated that 14 cases (29.2%) of incidental prostatic carcinoma showed chromosome alterations. The most frequent alterations were chromosomal losses of 8p (10.4%), 13q (6.3%), 5q (4.2%) and 18q (4.2%), and gains of 17p (10.4%), 17q (10.4%), 9q (6.3%) and 7q (4.2%). Minimal overlapping chromosomal regions of loss, indicative for the presence of tumor suppressor genes (TSGs), were mapped to 8p22 and 13q14.1-q21.3, and minimal overlapping regions of gain, indicative for the presence of oncogenes, were found at 9q34.2-qter, 17p12 and 17q24-qter. The statistical analysis displayed a significant association between chromosomal aberration detected by CGH and high Gleason score (P < 0.005) as well as between tumor categories T1a and T1b and chromosomal imbalance (P = 0.041). CONCLUSIONS: Studies directed at incidental prostatic carcinomas allow discovery of chromosomal changes in small and highly malignant tumors. Our results suggest that loss or gain of DNA in these regions are important in prostate cancer. This is the first study, which documents the spectrum of chromosomal changes in incidental prostatic carcinomas.     

Mapping of metastasis suppressor genes for prostate cancer by microcell-mediated chromosome transfer

Aim: To identify the metastasis suppressor genes for prostate cancer. Methods: A copy of human chromosomes was introduced into the highly metastatic Dunning R-3327 rat prostate cancer cells by the use of microcell-mediated chromosome transfer. Relationships between the size of human chromosomes introduced into microcell hybrid clones and the number of lung metastases produced by the clones were analyzed to determine which part of human chromosomes contained the metastasis suppressor gene (s) for prostate cancer. To determine portions of human chromosomes introduced, G-banding chromosomal analysis, fluorescence in situ hybridization analysis, and polymerase chain reaction analysis were performed. Results: Each of microcell hybrid clones containing human chromosomes 7, 8, 10, 11, 12, or 17 showed decreased ability to metastasize to the lung without any loss of ttmaorigenicity. This demonstrates that these human chromosomes contain metastasis suppressor genes for prostate cancer. Spontaneous deletion of portions of human chromosomes was observed in the human chromosome 7, 10, 11, 12, and 17 studies. In the human chromosome 8 study, irradiated microcell-mediated chromosome transfer was performed to enrich chromosomal ann deletions of human chromosome 8. Molecular and cytogenetic analyses of microcell hybrid clones demonstrated that metastasis suppressor genes on human chromosomes were located on 7q21-22, 7q31.2-32, 8p21-12, 10q11-22, 11p13-11.2, 12p11-q13, 12q24-ter, and 17pter-q23. KAI1 and MKK4/SEKI were identified as metastasis suppressor genes from 11p11.2 and 17p12, respectively. Conclusion: This assay system is useful to identify metastasis suppressor gene (s) for prostate cancer.     

Review of allelic loss and gain in prostate cancer

Summary There are three nearly ubiquitous genomic imbalances in prostate cancer cells: 1) loss of sequences from the short arm of chromosomes 8, 2) loss of sequences from the long arm of chromosome 13q, and 3) gain of sequences on the long arm of chromosome 8, particularly in advanced disease. Candidate tumor suppressor genes and oncogenes affected by this trio of consistent changes include the c-myc gene on chromosome 8q24, the RB gene at 13q14, and potentially multiple novel genes on the short arm of chromosome 8, with a gene located more proximally potentially involved in tumor initiation and a gene or genes located more distally involved in tumor progression. Loss of regions of chromosomes 2q, 5q, 6q, 7p and 7q, 9p, 10p and 10q, 16q, 17p and 17q, and 18q, and gain of regions of 1q, 2p, 3p and 3q, 7p and 7q, 11p, 17q, and Xq have also been detected in the range of 25–50% of tumors studied. Analysis of candidate tumor suppressor genes in these regions is still in its early stages. Similarly, potential oncogenes on a series of chromosomal arms which undergo frequent amplification remain essentially uncharacterized. The basic outline of the chromosomal aberrations in prostate cancer has been well established; the details of the story remain to be filled in. This paper reviews the advantages and disadvantages of various techniques for detection of genomic loss and gain in prostate cancer cells, and reviews published reports of loss and gain in prostate cancer, focusing primarily on reports using microsatellite analysis, Southern analysis, and comparative genomic hybridization. Fluorescence in situ hybridization (FISH) based analyses of selected regions are also reviewed.     

Genetic changes in stage pT2N0 prostate cancer studied by comparative genomic hybridization

OBJECTIVE: To identify chromosomal regions important for progression in clinically organ-confined prostate cancer, as the genetic changes underlying the development and progression of prostate cancer are poorly understood. MATERIALS AND METHODS: Comparative genomic hybridization (CGH) was used to search for DNA sequence copy-number changes in a series of 50 primary organ-confined prostate adenocarcinomas (pT2N0) removed by radical prostatectomy. RESULTS: CGH analysis indicated that 23 (46%) of the primary prostate adenocarcinomas showed chromosome alterations. The percentage of tumours with losses (38%) was higher than with gains (28%). Losses of 13q (24%), 8p (18%), 6q (10%), 16q (8%), 18q (6%) and 5q (6%) and gains of 17q (12%), 20q (12%), 9q (10%), 17p (8%) and 8q (6%) were the most frequent alterations. Amplifications were found at 8q24-qter. Minimal overlapping regions of loss, indicative of the presence of tumour-suppressor genes, were mapped to 13q21.1-q21.3 and 8p21.2, and minimal overlapping regions of gain, indicative of the presence of oncogenes, were found at 9q34.4-qter, 17q25-qter and 20q13.3-qter. There was a significant association between Gleason score and losses and gains (P = 0.003), and an association between chromosomal imbalance and high histological grade (P = 0.008). CONCLUSION: These results suggest that losses or gains of DNA in these regions are important for prostate cancer progression, and document the spectrum of chromosomal alterations in stage pT2N0 of clinically organ-confined prostate cancer.     

Comparative genomic hybridization reveals DNA copy number gains to frequently occur in human prostate cancer

BACKGROUND: Despite intensive studies over many years, there is only limited knowledge on the genetic changes underlying the development and progression of prostate cancer. No specific prostate carcinoma-related genetic event has yet been identified. METHODS: In order to gain an overall view of regional chromosome gains and losses, comparative genomic hybridization (CGH) was used on a series of 16 prostate adenocarcinomas. Five benign prostate hyperplasia (BPH) samples were also evaluated. RESULTS: Using CGH, chromosome alterations were observed in 81% of the prostate carcinomas analyzed. Gains of DNA copy numbers were found as the predominant imbalance, with chromosomes 3q (56%), 12q (56%), 8q (50%), Xq (50%), 4 (44%), 6q (44%), 5 (38%), 7q (38%), 9p (38%), and 13q (31%) being most frequently involved. Whereas DNA copy number gains comprised the whole chromosome or almost a whole arm of chromosomes 4, 5, 6, 9, and 13, the minimal overlapping regions on the other chromosomes were mapped to 3q25-q26, 8q21-q22, 12q13-q21, 7q31, and Xq22-q25. High-level amplifications were not found. Other chromosomes with nonrandom gains or losses of DNA sequences were discovered. The five BPH samples were found to be normal. CONCLUSIONS: Amplification events at different chromosomal sites seem important in prostate cancer development. A new chromosome region with DNA copy number gains was identified on 12q, while other regions on 3q, 7q, 8q, and Xq were confirmed or narrowed down, indicating a possible role of known or putative protooncogenes in these regions for prostate cancer growth. Our low detection rate of DNA losses may to some part be explained by CGH immanent technical limitations.     

Contribution of known and unknown susceptibility genes to early-onset diabetes in scandinavia: evidence for heterogeneity

In an attempt to identify novel susceptibility genes predisposing to early-onset diabetes (EOD), we performed a genome-wide scan using 433 markers in 222 individuals (119 with diabetes) from 29 Scandinavian families with > or =2 members with onset of diabetes < or =45 years. The highest nonparametric linkage (NPL) score, 2.7 (P < 0.01), was observed on chromosome 1p (D1S473/D1S438). Six other regions on chromosomes 3p, 7q, 11q, 18q, 20q, and 21q showed a nominal P value <0.05. Of the EOD subjects in these 29 families, 20% were GAD antibody positive and 68% displayed type 1 diabetes HLA risk alleles (DQB*02 or 0302). Mutations in maturity-onset diabetes of the young (MODY) 1-5 genes and the A3243G mitochondrial DNA mutation were detected by single-strand conformation polymorphism and direct sequencing. To increase homogeneity, we analyzed a subsample of five families with autosomal dominant inheritance of EOD (greater than or equal to two members with age at diagnosis < or =35 years). The highest NPL scores were found on chromosome 1p (D1S438-D1S1665; NPL 3.0; P < 0.01) and 16q (D16S419; NPL 2.9; P < 0.01). After exclusion of three families with MODY1, MODY3, and mitochondrial mutations, the highest NPL scores were observed on chromosomes 1p (D1S438; NPL 2.6; P < 0.01), 3p (D3S1620; NPL 2.2; P < 0.03), 5q (D5S1465; NPL 2.1; P < 0.03), 7q (D7S820; NPL 2.0; P < 0.03), 18q (D18S535; NPL 1.9; P < 0.04), 20q (D20S195; NPL 2.5; P < 0.02), and 21q (D21S1446; NPL 2.2; P < 0.03). We conclude that considerable heterogeneity exists in Scandinavian subjects with EOD; 24% had MODY or maternally inherited diabetes and deafness, and approximately 60% were GAD antibody positive or had type 1 diabetes-associated HLA genotypes. Our data also point at putative chromosomal regions, which could harbor novel genes that contribute to EOD.