应用M-FISH和CGH技术研究肺腺癌基因组变化

[目的]分析肺腺癌中染色体异常变化和基因改变，探讨肺腺癌细胞遗传物质的改变与肺腺癌发生发展之间的关系。[方法]应用M-FISH技术，检测3株肺腺癌细胞株的染色体数目及结构畸变情况．应用CCH技术对50例肺腺癌组织提取的全基因组DNA进行检测，以了解肺腺癌全基因组的变化。[结果]M-FISH结果显示肺腺癌细胞中存在许多复杂的染色体重排，5、6、11、12、17号染色体最频繁参与染色体间的易位。CGH发现，在50例肺腺癌标本基因组中，最常见的扩增区域是1q、2p、3q、5p、5q、7p、8q、11q、12q、14q、16p、17q、19q、20q、21q、22q。最常见的缺失区域是2q、3p、4p、5q、7q、8p、9p、13q、14q、17p。其中最常见的扩增位点是16p13，阳性率达50％，最常见的缺失位点是8p22，阳性率达38％。[结论]M-FISH和CGH技术是研究肺腺癌基因组变化的强有力工具，该实验中发现的基因可能代表了与肺腺癌的病理、诊断相关的候选基因。     

比较基因组杂交技术检测肝细胞癌染色体异常及其临床意义

目的探讨肝细胞癌染色体异常及其临床意义。方法运用比较基因组杂交技术检测25例肝细胞癌染色体DNA异常情况,并与临床指标作相关分析。结果 25例肝癌均存在不同程度的染色体DNA拷贝数的扩增或缺失,较为常见的染色体DNA异常是+1q(72%)、+1p(64%)、+2q(48%)、+2p(48%)、+5q(48%)、+Xq(48%)、+7q(44%)、-4q(48%)、-16p(48%)、-8p(40%)、-17p(36%);相关分析显示+17p、+18p、-8p、-13q、-11q、-8q染色体异常事件与临床指标部分相关。结论肝细胞癌存在明显的染色体异常,部分染色体异常事件是非随机性的,可能与肝癌的发生、发展有关,并与肿瘤的生物学行为和预后相关。     

卵巢癌顺铂耐药细胞系及其亲代细胞的比较基因组杂交研究

目的：探讨人卵巢癌顺铂耐药细胞株COC1/DDP及其药物敏感细胞株COC1在基因组DNA水平上可能存在的差异,以及这种差异在肿瘤耐药性产生中的意义.方法：采用比较基因组杂交技术分析COC1和COC1/DDP两组癌细胞间基因组的不平衡,即DNA丢失或扩增.结果：COC1细胞系具有广泛的染色体改变,染色体出现扩增的有1p21-31、2q14-24、3q25-29、8q22-24、12p11-12、19p12q12、20q12-13,出现缺失的染色体有4、13q22-31、18q12-21.COC1/DDP细胞系也有较广泛的染色体改变,出现扩增的有6q21-24、17q21-25、18q21-23,出现缺失的有10q11-22、16q12-22、17p11-12.结论：卵巢癌耐药及亲本细胞中存在着广泛的染色体变异,其中6q、17q、18q、10q、16q、17p中的一些已知或未知基因可能参与COC1/DDP耐药性的产生.     

采用比较基因组杂交方法分析原发性食管癌染色体异常

背景与目的:有研究表明原发性食管癌常有染色体的改变,包括染色体基因组异常扩增和缺失.比较基因组杂交技术可以显示这些染色体的异常变化.本实验采用比较基因组杂交技术研究和分析原发性食管癌染色体基因组的变化特点及其与预后的关系.方法:采用比较基因组杂交技术检测16例食管癌组织中染色体的异常改变,并分析染色体异常与预后的关系.研究的病例中7例食管癌术后2年内死亡(对照组),9例术后生存3年以上(生存组).结果:食管癌患者中多数染色体基因组发生改变,最常见的染色体基因组高扩增频率发生在1q/p,2q/p,3q,5q/p,8q/p,9q/p,11q/p,17和20q/p染色体区段上,在染色体1q/p,4p,9p,18q和xp中常见染色体基因缺失.染色体7q/p和19扩增频率和染色体4q/p和18q缺失频率,生存组与对照组间存在显著性差异.结论:食管癌患者染色体区段基因易发生异常扩增和缺失,生存组与对照组存在明显差异.     

广西地区乙肝病毒／黄曲霉毒素B1双暴露相关性肝细胞性肝癌微阵列比较基因组学的研究

目的研究乙肝病毒／黄曲霉毒素B1双暴露相关性肝细胞性肝癌（hepatocellularcarcinoma,HCC）染色体遗传学畸变的特点。方法将32例手术切除经病理证实为HCC的癌组织,按照乙肝病毒与黄曲霉毒素的暴露情况分为4个亚组：A组为HBV（＋）／AFB,（＋）10例;B组为HBV（＋）／AFB1（-）10例;C组为HBV（-）／AFB1（＋）6例;D组为HBV（-）／AFB1（-）6例。应用微阵列比较基因组杂交技术（ArrayCGH）检测分析其22对染色体DNA拷贝数的变化。结果32例HCC样本中,共发现573个染色体畸变区段（chromosomalaberrations,CNAs）。其中1q、4p、5p、6p、7p、8q、10p、17q、20p、20q和X主要表现为扩增区段;1p、2q、4q、8p、9p、10q、11q、13q、14q、16p、16q、17p、19p、19q、21q、22q和Y主要表现为缺失区段。同时,共检测出25个染色体发生高频畸变的区段（recurrentlyalteredregions,RARs）,其中lq21．1-q44、5p13．2-p15．3、6p12．1-p25．2、7q11．2-q35、8q11．2-q24．3、17q12-q25．2、18q12．3-q22．3和x为高频率扩增区段,而lp31．1-p36．2、2q23．2-q37．2、4q12-q35．2、6q14．1-q26、8p12-p23．2、9p21．1-p24．2、10q21.3-q26．2、13q12．1-q21．1、14q21．3-q32．2、16p12．1-p13．2、16q12．1-q24．1、17p12-p1313、19p13．1-p13．3、19q13．2-q13．4、21q21．3-q22．2、22q11．2-q13．2和Y染色体为高频缺失区段。8p12-p23．2缺失的发生率在进展期HCC（TNM分期为Ⅲ～Ⅳ期）中明显高于早期HCC（TNM分期为I～Ⅱ期）（仁0．038）。4q12-q35．2、13q12．1-q21．1的缺失及7q21．1-q35的扩增发生率在A组中最高。Cox模型分析结果示：在单因素分析中AFP水平、肿瘤大小、TNM分期、BCLC分期、侵袭与转移的发生、8p12-p23．2的缺失以及19p13．1-p13．3的缺失等为影响患者无瘤生存时间的危险因素（P〈0．05）.而在多因素分析中AFP水平、TNM分期以及8p12-p23．2的缺失等为影响患者无瘤生存时间的危险因素（P〈0．05o结论广西地区HCC染色体遗传学改变具有多样性,其中染色体19p13．1．p13-3的高频缺失可能为广西地区HCC特有的分子生物学特征之一。染色体8p12-p23．2的缺失可能为HCC的晚期事件,并且与患者的不良预后有关。染色体4q12-q35．2、13q12．1-q21．1缺失及7q21．1-q35扩增可能与HBV／AFB。双因素的协同致癌作用有关。     

原发性肺癌肿瘤组织染色体变异比较基因组杂交分析

目的：分析原发性肺癌肿瘤组织染色体异常变化，了解肺癌组织染色体畸变规律。方法：应用比较基因组杂交技术分析55例原发性肺癌患者肿瘤组织染色体结果：原发性肺鳞癌常见染色体扩增区是2q、5p、11q、22q，常见缺失区是1p、4q、5q、6q、8p、9p、10q、11p、13q、18q、21q。肺腺癌常见扩增区是5p、8q、11q，常见缺失区是10p、19。腺鳞癌、肺泡细胞癌、小细胞癌等染色体变化各有不同。结论：原发性肺癌存在广泛的遗传物质不平衡现象．不同病理分型的染色体基因扩增和缺失可能是其发生、发展的基础。     

利用比较基因组杂交技术分析腺泡状横纹肌肉瘤染色体的变化特征

目的 探讨腺泡状横纹肌肉瘤(ARMS)基因组DNA的变化特征.方法 采用一步法逆转录聚合酶链反应,检测10例原发性ARMS患者标本中PAX3-FKHR和PAX7-FKHR融合基因的mRNA表达.采用比较基因组杂交(CGH)技术,分析ARMS染色体基因组的变化特征.根据融合基因的表达情况以及患者的临床病理特征进行分组比较.同时收集ARMS细胞株A204作为对照.结果 10例原发性ARMS患者标本中,PAX3-FKHR融合基因表达6例,PAX7-FKHR融合基因表达2例,2例未检测到融合基因表达.CGH分析结果 显示,10例ARMS标本中,基因组DNA扩增频率最高的染色体臂为12q,占70.0%;其他依次为2p、6p、6q、10q、2q、4q、15q、1p、9q、14q和18q,均≥30.0%;其中常见的最小重叠扩增区段为12q13、2p24、6p21和2q31.基因组DNA缺失频率最高的染色体臂是3p、6p、20q和21q,均>30.0%;缺失部位比较分散,最小重叠缺失区段无集中趋势.伴有融合基因表达的8例ARMS标本中,基因组DNA扩增频率最高的染色体臂是12q,占87.5%;其他依次为10q、2p、2q、6p、6q、1p、4q、8q、11q、14q和15q,均>30.0%.基因组DNA缺失频率最高的染色体臂是3p、5q、6p、1q、8p、11p、20q和21q,均>30.0%.ARMS的染色体改变与组织学分级、临床分期、年龄和性别均无关(均P>0.05).结论 12q、2p、6p、6q、10q、2q、4q、15q、1p、9q、14q和18q的扩增以及3p、6p、20q和21q的缺失可能与ARMS的发病相关,12q的扩增还可能与PAX3-FKHR和PAX7-FKHR融合基因的表达相关.     

食管癌原发灶与淋巴结转移灶细胞染色体变化特征的比较

背景与目的:食管癌早期可发生局部淋巴或血行转移,这是导致复发和预后差的主要原因。但是,食管癌转移发生的分子机制尚不清楚。本研究旨在分析食管癌原发灶和淋巴结转移灶肿瘤细胞染色体变化的特征,寻找或定位与食管癌转移相关基因,加深对其转移机制的了解。方法:应用比较基因组杂交技术(comparativegenomichybridization,CGH)分析15例食管癌患者原发灶和其对应的淋巴结转移灶的染色体基因组改变。结果:最常见染色体DNA拷贝数增加的部位是3q,8q,6p,20p,5p,18p,2p,2q,1q;常见的染色体DNA拷贝数丢失的部位是10p,10q,17p,18q,4p,13q。其中,最有意义的发现是6p增加(原发灶:2/15,13%,转移灶:7/15,47%),20p增加(原发灶:5/15,33.3%,转移灶:11/15,73.3%)。第二个发现是10p丢失(原发灶:2/15,13.3%,转移灶:8/15,53%),10q丢失(原发灶:2/15,13.3%,转移灶:7/15,46.6%)。结论:食管癌原发灶和淋巴结转移灶细胞染色体基因组改变最显著的部位是6p,20p的增加和10p,10q的丢失;这些部位可能存在与食管癌细胞淋巴结转移相关的基因。     

比较基因组杂交技术检测肝细胞癌染色体异常及其临床意义

目的探讨肝细胞癌染色体异常及其临床意义。方法运用比较基因组杂交技术检测25例肝细胞癌染色体DNA异常情况,并与临床指标作相关分析。结果25例肝癌均存在不同程度的染色体DNA拷贝数的扩增或缺失,较为常见的染色体DNA异常是＋1q（72％）、＋1p（64％）、＋2q（、48％）、＋2p（48％）、＋5q（48％）、＋Xq（48％）、＋7q（44％）、-4q（48％）、-16p（48％）、-8p（40％）、-17p（36％）;相关分析显示＋17p、＋18p、-8p、-13q、-11q、-8q染色体异常事件与临床指标部分相关。结论肝细胞癌存在明显的染色体异常,部分染色体异常事件是非随机性的,可能与肝癌的发生、发展有关,并与肿瘤的生物学行为和预后相关。     

非小细胞肺癌分子病理学的研究

目的　探讨上海地区人肺癌发生及发展过程中的分子病理学模式。方法　采用DNAslotblot、PCR、PCR SSCP等方法 ,先后检测 2 0 0例NSCLC组织DNA标本中C erbB2、C myc、EGFR癌基因扩增 ,抑癌基因中p5 3基因外显子 5～ 8点突变、p15基因的纯合性丢失 ,以及某些与肺癌相关的染色体 3p及 17p13 .3位点的杂合性丢失 (LOH)。结果　多种癌基因共扩增率与肺癌TNM分期呈正相关 (P <0 .0 0 1)。p5 3基因外显子 5～8点突变率为 49.2 % ( 3 1/63 ) ,其中以外显子 8为主。肺癌组织中p15基因出现高频率纯合性丢失 ,并与肺癌TNM分期密切相关 (P <0 .0 0 5 )。 17p13 .3杂合性丢失率为 40 % ( 8/2 0 ) ,并与p5 3基因的点突变相关联。 3p14及 3p2 5位点处的杂合性总丢失率可高达 66.7% ( 10 8/162 ) ,其中肺腺癌中 3p14及 3p2 5二位点的共丢失率明显高于鳞癌 (P <0 .0 5 )。结论　根据上述结果 ,提出上海市区居民的非小细胞肺癌分子病理学的初步模式 :癌前期病变时已可出现 3p丢失 ,原位癌时以p5 3基因突变及 17p13 .3丢失为主 ,浸润癌及向转移性癌过渡时有多种癌基因C myc、C erbB2及EGFR癌基因共扩增 ,并出现p15基因纯合性丢失。     

Comparative genomic hybridization analysis on male breast cancer

The spectrum of genetic alterations in primary male breast cancer is not well established. We analyzed chromosomal imbalances in 39 tumor samples from primary male breast cancer by comparative genomic hybridization (CGH) and correlated CGH findings with clinicopathological factors. Chromosomal gains were most frequent at 1q (46%), 8q (46%), 16p (36%), 17q (36%), Xq (28%), 20q (26%) and Xp (18%). Losses were most commonly observed at 8p (36%), 16q (28%), 13q (28%), 6q (18%), 11q (18%) and 22q (18%). Gains at 16p, 20q and Xq and losses at 13q correlated significantly with higher degree of cytogenetic complexity. Significant associations with clinicopathological factors were observed for +8q and -16q with larger tumor size and -16q with lower proliferative activity and lower grade of malignancy. A comparison with reported CGH data from female breast cancer showed a similar pattern of chromosomal imbalances, including +1q, -8p, +8q, -13q, +16p, -16q, +17q and +20q. Our results indicate that male breast cancer shares a common pattern of imbalances with female breast cancer, suggesting that similar genetic events may underlie the development and progression of male and female breast cancer.     

Genetic analysis of head and neck squamous cell carcinoma using comparative genomic hybridisation identifies specific aberrations associated with laryngeal origin

Head and neck squamous cell carcinoma (HNSCC) demonstrates significant differences in the biological and clinical behaviour of tumours found at different sub-sites. We investigated the genetic profiles of 68 carcinomas (larynx n=35, hypopharynx n=19, oropharynx n=14) using chromosomal comparative genomic hybridisation in order to identify sub-site specific differences. Multiple genetic aberrations were found throughout the tumour genomes, including +3q (82%), -3p (75%), +8q (66%), +5p (49%), +7q (49%), +1q (47%), -4p (46%), -11q (46%), -13q (46%), -5q (44%), +11q (43%) and +12p (43%). The mean number of chromosomal arms with at least one aberration was 15. Laryngeal carcinomas (LSCC) were found to have significantly more aberrations on chromosomal arms than oropharyngeal carcinomas (OpSCC); (mean of 17 vs. 11, respectively (p=0.011). It was noted that -4p, +8q, +12q, and -18q were significantly associated with LSCC when compared with both hypopharyngeal SCC (HpSCC) and OpSCC. HpSCC was significantly associated with -2q whereas no aberrations were found to be significantly associated with OpSCC. In conclusion a large number of common chromosomal aberrations are associated with HNSCC however in addition further aberrations are significantly associated with individual sub-sites of head and neck cancer. These aberrations may be responsible for the diverse biological behaviour of these different tumour types. Further research is required to identify the specific genes associated with these chromosomal regions and evaluate their individual impact on disease progression.     

Chromosomal aberrations in human hepatocellular carcinomas associated with hepatitis C virus infection detected by comparative genomic hybridization.

Thirty-five hepatocellular carcinomas (HCCs) associated with hepatitis C virus (HCV) were analysed by comparative genomic hybridization (CGH), to screen for changes in copy-number of DNA sequences. Chromosomal losses were noted in 1p34-36 (37%), 4q12-21 (48%), 5q13-21 (35%), 6q13-16 (23%), 8p21-23 (28%), 13q (20%), 16q (33%) and 17p13 (37%). Gains were noted in 1q (46%), 6p (20%), 8q21-24 (31%) and 17q (43%). High level gains indicative of gene amplifications were found in 7q31 (3%), 11q13 (3%), 14q12 (6%) and 17q12 (3%); amplification at 14q12 may be characteristic for HCCs. No significant difference in chromosomal aberrations was noted between carcinomas associated with HCV-infection in our study and those reported earlier in HCCs infected with hepatitis B virus (HBV), indicating that both HBV- and HCV-related carcinomas may progress through a similar cascade of molecular events.     

Patterns of chromosomal imbalances defines subgroups of breast cancer with distinct clinical features and prognosis. A study of 305 tumors by comparative genomic hybridization

Chromosomal copy number aberrations (CNAs) are common in breast cancer and involve genomic regions in a frequency and combination, suggesting distinct routes of tumor development. We studied chromosomal gains (+) and losses (-) by comparative genomic hybridization from a series of 305 unselected primary invasive breast cancers. CNAs were observed in >90% of the tumors and involved all chromosomal arms in various frequencies, the most common being +1q (55%), +8q (41%), +16p (40%), +17q (28%), -13q (27%), -16q (22%), +20q (19%), -8p (18%), and +11q (16%). Eighteen pairs of CNAs were revealed as significantly associated using Fisher's exact test with Bonferroni correction, the most common pairs being -8p/+8q, +17q/+20q, and -4q/-13q. To study more complex relationships between individual CNAs, principal component analysis and distance-based tree modeling were performed independently. Three distinct patterns of CNAs were observed. Group A was defined by +1q, +16p, and -16q, group B by +11q, +20q, +17q, and -13q, and group C by -8p and +8q. Group A was correlated to positive estrogen receptor and progesterone receptor (PgR) status (P < 0.001 and P < 0.05, respectively). Groups B and C were correlated to DNA nondiploidy (P < 0.001 and P < 0.05), high histological grade and lymph node positivity (P < 0.05), and group B also to high proliferation rate, large primary tumor size (P < 0.001), and negative PgR status (P < 0.05). Patients with aberrations in group A only had a significantly higher breast cancer survival rate than all other patients. The worst survival was seen for patients with aberrations in group C only along with the patients displaying aberrations from all CNA pattern groups (ABC). The 5-year survival rates vary from 96% in group A to 56% in group C. These correlations were independent of node status, tumor size, and PgR status in a multivariate analysis. We conclude that patterns of copy number gains and losses define breast tumors with distinct clinicopathological features and patient prognosis.     

Comparative genomic hybridization analysis detected frequent overrepresentation of chromosome 3q in squamous cell carcinoma of the lung

The aim of this study was to provide cytogenetic data about squamous cell carcinomas of the lung and to evaluate their characteristic alterations and histogenetic relations. We analyzed 41 squamous cell lung carcinomas by comparative genomic hybridization (CGH) technique. CGH was performed using directly fluorochrome-conjugated DNA. Chromosomal regions where the mean ratio fell below 0.75 were therefore considered to reflect DNA copy number loss (underrepresentation), whereas regions where the mean ratio exceeded 1.25 were considered gains (overrepresentations) in the tumor genome. Overrepresentations were considered to be high-level amplification when the fluorescence ratio exceeded 1.5. Chromosomal imbalances were observed in every case. Copy number gains frequently were detected at 3q, 5p, 8q, 12p, and Xq. Losses were found at 16p, 4q, 5q, 3p, 17p, and 16q. DNA amplifications were observed at 12 regions: 3q26.1-27, 8q13-23.1, 12p12.3-pter, 12q15, 2p14-16, 4q28-31.2, 5p13.1-pter, 6q21-22.3, 7p11.2-13, 13q21.2-32, 18p11.2-pter, and 20p11.2-pter. Gains on 3q were frequently detected not only in the more than 3 cm group (79%) but also in the 3 cm or less group (77%). The mean frequency of gained or lost chromosomal regions was 7.2+/-4.7 in the 3 cm or less group (n=13) and 10.2+/-6.3 in the more than 3 cm group (n=28) (P=0.4503). The mean frequency of gained or lost chromosomal regions was significantly higher in the carcinoma with lymph node metastasis group (12.5+/-7.6 regions) (n=12) than in the carcinoma without lymph node metastasis group (7.9+/-4.6) (n=29) (P=0.0251). In conclusion, an increased copy number at 3q may contribute to the development of squamous cell carcinoma of the lung.     

Comparative genomic hybridization of esophageal squamous cell carcinoma: correlations between chromosomal aberrations and disease progression/prognosis.

BACKGROUND: Esophageal carcinoma is a major cause of cancer-related deaths among males in Taiwan. However, to date, the genetic alterations that accompany this lethal disease are not understood. METHODS: Chromosomal aberrations of 46 samples of esophageal squamous cell carcinoma (EC-SCC) were analyzed by comparative genomic hybridization (CGH), and their correlations with pathologic staging and prognosis were analyzed statistically. RESULTS: In total, 321 gains and 252 losses were found in 46 tumor samples; thus, the average gains and losses per patient were 6.98 and 5.47, respectively. Frequent gain abnormalities were found on chromosome arms 1q, 2q, 3q, 5p, 7p, 7q, 8q, 11q, 12p, 12q, 14q, 17q, 20q, and Xq. Frequent deletions were found on chromosome arms 1p, 3p, 4p, 5q, 8p, 9p, 9q, 11q, 13q, 16p, 17p, 18q, 19p, and 19q. It was found that deletions of 4p and 13q12-q14 and gain of 5p were significantly correlated with pathologic staging. Losses of 8p22-pter and 9p also were found more frequently in patients with advanced disease. Gain of 8q24-qter was seen more frequently in patients with Grade 3 tumors. A univariate analysis found that pathologic staging; gains of 5p and 7q; and deletions of 4p, 9p, and 11q were significant prognostic factors. However, pathologic staging became the only significant factor in a multivariate analysis. CONCLUSIONS: CGH not only revealed novel chromosomal aberrations in EC-SCC, but also found possible genotypic changes associated with disease progression. Despite all of the possible associations of chromosomal aberrations with disease progression, the most important prognostic factor for patients with EC-SCC was pathologic staging.     

Chromosomal alterations in lung adenocarcinoma from smokers and nonsmokers

The etiology of lung tumors arising in nonsmokers remains unclear. Although mutations in the K-ras and p53 genes have been reported to be significantly higher in smoking-related lung carcinomas, in the present study we performed a more comprehensive analysis in search of additional genetic changes between lung adenocarcinoma from tobacco- and non-tobacco-exposed patients. We selected a matched cohort of 18 lifetime nonsmoking and 27 smoking patients diagnosed with primary adenocarcinoma of the lung and searched for chromosomal alterations in each tumor by testing normal and tumor tissue with 54 highly polymorphic microsatellite markers located on 28 different chromosomal arms. Allelic losses or gains at chromosomal arms 3p (37 versus 6%), 6q (46 versus 12%), 9p (65 versus 22%), 16p (28 versus 0%), 17p (45 versus 11%), and 19p (58 versus 16%) were present significantly more often in adenocarcinomas from smokers than from nonsmokers. Chromosomal arms showing allelic imbalance in lung tumors from nonsmokers were rare but occurred more often at 19q (22%), 12p (22%), and 9p (22%). The FAL (fractional allelic loss or gain) is defined as the percentage of chromosomal arm losses/gains among the total informative chromosomal arms. Tumors from smokers harbored higher levels of FAL (13 (48%) of 27 showed FAL > or = 0.3) compared with the lung tumors from the nonsmoker patients (2 (11%) of 18 showed FAL > or = 0.3; P = 0.02; odds ratio, 0.13; 95% confidence interval, 0.01-0.79). Our data demonstrate that widespread chromosomal abnormalities are frequent in lung adenocarcinoma from smokers, whereas these abnormalities are infrequent in such tumors arising in nonsmokers. These observations support the notion that lung cancers in nonsmokers arise through genetic alterations distinct from the common events observed in tumors from smokers.     

Frequent gains and losses of specific chromosome segments in human ovarian carcinomas shown by comparative genomic hybridization

Total genomic DNA obtained from 24 ovarian carcinomas was examined for genomic imbalances by comparative genomic hybridization (CGH). A varying number of gains and losses (1 up to 31) of specific chromosomal segments was detected per tumor. Chromosomal segments which were most often present in increased copy numbers were (in decreasing order): 1q21, 8q24, 8q23, 3q26, 12p12-p13, 20q, 7q31, and 7q33-qter. Loss of material was found most frequently at 16q12, 13q13-q14, Xq, 8p21-p22, 5q13-q14, and 5q21. All these chromosomal segments involved in gains and losses may carry gene loci playing a more or less causal role in the process of ovarian malignancies. Based on these findings CGH can be regarded as a valuable tool for rapid screening of genomic imbalances in human tumors.     

Chromosomal changes during development and progression of prostate adenocarcinomas

Chromosomal copy number changes were investigated in 16 prostate carcinomas, 12 prostatic intraepithelial neoplasias (PIN; 4 low-grade and 8 high-grade) adjacent to the invasive tumour areas, and 5 regional lymph node metastases. For this purpose, comparative genomic hybridization (CGH) was performed and a copy number karyotype for each histomorphological entity was created. CGH on microdissected cells from non-neoplastic glands was carried out on 3 different cases to demonstrate the reliability of the overall procedure. None of the non-neoplastic tissue samples revealed chromosome copy number changes. In PIN areas, chromosomal imbalances were detected on chromosomes 7, 8q, Xq (gains), and on 4q, 5q, 8p, 13q and 18q (losses). In the primary tumours, recurrent (at least 25% of cases) gains on chromosomes 12q and 15q, and losses on 2q, 4q, 5q, Xq, 13q and 18q became apparent. Losses on 8p and 6q as well as gains on 8q and of chromosome 7 were also detected at lower frequencies than previously reported. The pooled CGH data from the primary carcinomas revealed a novel region of chromosomal loss on 4q which is also frequently affected in other tumour entities like oesophageal adenocarcinomas and is supposed to harbour a new tumour suppressor gene. Gains on chromosome 9q and of chromosome 16 and loss on chromosome 13q were observed as common aberrations in metastases and primary tumours. These CGH results indicate an accumulation of chromosomal imbalances during the PIN-carcinoma-metastasis sequence and an early origin of tumour-specific aberrations in PIN areas.