P73表达在人类肿瘤中的意义

原癌基因（proto-oncogene）的激活和/或抑癌基因（tumor suppressor gene）的缺失和灭活是恶性肿瘤发生、发展的分子生物学基础.P53基因是迄今为止发现的与人类肿瘤相关性最高的抑癌基因,其第一个被发现的家族成员P73基因作为候选的抑癌基因受到学者们的广泛关注.本文对P73基因在人类肿瘤中的表达及意义作一综述.     

肿瘤遗传学研究进展

对肿瘤遗传学富有成果的探索是从７０年代开始的，人们从细胞和分子遗传学水平对肿瘤的遗传物质－染色体和ＤＮＡ的分析，发现凡是肿瘤细胞都伴有染色体畸变。近年来研究发现人类正常细胞中存在癌基因和抗癌基因，二者的相互作用是癌发的关键。这一突破性研究进展，使肿瘤遗传学步入全新领域。     

癌组织中的遗传不稳定性的RAPD分析(简报)

肿瘤仍然是导致人类死亡的重要原因,由于缺乏深刻了解癌症的发生机制,尽管在过去25年中肿瘤的诊断和治疗都取得很大的进展,但肿瘤病人的存活率并没有显著的提高。目前有很多癌基因和抑癌基因如P16、P53、P73、ras、DCC和RB等     

一种高突变频率法发现候选癌基因的探究

近几年来,随着我国基因技术的不断发展,已对多种癌基因组进行了细胞突变检查,为候选癌基因的发现提供参考依据。当前,对候选癌基因的研究成果众多,但大多是发现突变频率较高的候选癌基因,而忽视了突变频率低的候选癌基因。为此,本文特提出一种新的方法发现候选癌基因,以望对后期的候选癌基因的发现工作提供技术借鉴。     

反义核酸在肿瘤研究中的应用

反义核酸研究已活跃于肿瘤研究及基因治疗领域,反义核酸通过碱基配对待异性地抑制基因表达,因此为研究肿瘤中癌基因和生长因子的功能及癌基因突变检测提供了更为有效的手段,并为肿瘤的基因治疗提供了可能途径.文章综述了反义核酸在基因治疗中所面临的问题及部分解决办法.     

分子细胞遗传学在软组织肿瘤中的应用

软组织肿瘤是发生于纤维组织、脂肪组织、平滑肌、骨骼肌、滑膜等间叶组织的一组病因复杂,组织形态各异,临床表现多样的肿瘤.软组织肉瘤是此类肿瘤中的一小部分,以独特的临床袁现和特异性的遗传学改变为特点,虽然占人类所有恶性肿瘤的比例不到1%[1],但它们同样严重威胁着人类的生命并具有重要的诊断和治疗意义.随着组织化学染色、电镜技术和免疫组化技术等辅助手段的广泛应用,人们对软组织肿瘤的发生、发展和分类、诊断等方面有了更深刻的认识,特别是对其分子水平的研究表明除癌基因和抑癌基因的点突变之外,染色体易位和缺失所致的基因重排和丢失也是软组织肿瘤发生的重要分子机制.这使得分子细胞遗传学在软组织肿瘤研究中具有了重要作用和特殊意义.本综述通过分析分子细胞遗传学技术在软组织肿瘤的分类、诊断及预后等方面的应用,客观评价了此技术的作用、优缺点及未来的发展方向.     

脆性组氨酸三联体（FHIT）基因

人类第３号染色体上的基因座在不同的肿瘤组织中出现高频率的杂合性丢失（ＬＯＨ），提示该部位可能是抑癌基因潜伏的位点。最近克隆的脆性组氨酸三联体基因（ＦＨＩＴ）可能是定位于染色体３ｐ１４．２的一个抑癌基因，该基因在肿瘤组织中广泛地缺失为研究肿瘤发生机制提供了新线索。     

P53肿瘤抑制基因的研究与进展

Ｐ５３肿瘤抑制基因的研究与进展徐清,汤雪明（上海第二医科大学细胞生物学实验室２０００２５）Ｐ５３基因是目前癌基因和抑癌基因研究中最引人注目的新星。１９８１年Ｗｅｉｎｂｅｒｙ等人首先报道人癌基因分离成功,癌基因的研究成为肿瘤研究的热点“’１１９８６年人...     

错配修复基因与涎腺肿瘤的关系

错配修复(mismatch repair,MMR)是DNA复制后的一种修复机制,对维持基因组稳定起重要作用.错配修复基因功能缺陷是继癌基因激活、抑癌基因失活之后又一肿瘤的发生、发展机制,错配修复基因的异常表达与全身多种肿瘤相关.涎腺肿瘤为口腔颌面部常见肿瘤之一,具有与其他系统肿瘤相似的组织学类型,多来源于肌上皮.近年来,有关涎腺肿瘤与错配修复基因的关系正逐步成为研究热点,本文就错配修复基因的组成、作用机制以及与涎腺肿瘤发生、发展的关系作一综述.     

人脑原发性肿瘤癌基因扩增和重排的研究

作者对52例人脑原发性肿瘤和5例正常人脑DNA中c-myc、L-myc、Nmyc、erbB、c-fos、sis及Ha-ras等七种癌基因的扩增和重排进行了研究,发现多数胶质瘤中有c-myc、L-myc、erbB及c-fos等癌基因的扩增,少数胶质瘤和脑膜瘤中发现myc家族癌基因的限制性酶切区带位置有多态性变化;同时还观察到原发性脑瘤中存在两种或两种以上癌基因的扩增和重排现象。作者对癌基因与人脑原发性肿瘤的关系进行了讨论。     

人类蛋白组学草图的肺癌分子标记物初探

传统的肺癌分子标记物探索通常基于基因组或者转录组研究,而基于蛋白质水平的肺癌分子标记物探索通常局限在低通量水平。质谱技术已经开始产生高通量的全局正常及癌症蛋白组。我们采用开源统计软件R对人类蛋白组学草图数据及已发表的肺癌蛋白质组学数据进行二次分析,筛选出91个潜在的候选肺癌分子标记物。基因注解分析显示候选肺癌基因富集了和代谢、TP53通路以及MicroRNA调控等相关的基因。最后,利用Human Protein Atlas数据库及Pubmed对前20候选标记物进行验证,结果显示大部分候选肺癌基因大多能够得到验证。可见数据挖掘在即将到来的质谱推动的组学大数据时代将发挥重要作用。     

Genes suppressed by DNA methylation in non-small cell lung cancer reveal the epigenetics of epithelial–mesenchymal transition

Background

DNA methylation is associated with aberrant gene expression in cancer, and has been shown to correlate with therapeutic response and disease prognosis in some types of cancer. We sought to investigate the biological significance of DNA methylation in lung cancer.

Results

We integrated the gene expression profiles and data of gene promoter methylation for a large panel of non-small cell lung cancer cell lines, and identified 578 candidate genes with expression levels that were inversely correlated to the degree of DNA methylation. We found these candidate genes to be differentially methylated in normal lung tissue versus non-small cell lung cancer tumors, and segregated by histologic and tumor subtypes. We used gene set enrichment analysis of the genes ranked by the degree of correlation between gene expression and DNA methylation to identify gene sets involved in cellular migration and metastasis. Our unsupervised hierarchical clustering of the candidate genes segregated cell lines according to the epithelial-to-mesenchymal transition phenotype. Genes related to the epithelial-to-mesenchymal transition, such as AXL, ESRP1, HoxB4, and SPINT1/2, were among the nearly 20% of the candidate genes that were differentially methylated between epithelial and mesenchymal cells. Greater numbers of genes were methylated in the mesenchymal cells and their expressions were upregulated by 5-azacytidine treatment. Methylation of the candidate genes was associated with erlotinib resistance in wild-type EGFR cell lines. The expression profiles of the candidate genes were associated with 8-week disease control in patients with wild-type EGFR who had unresectable non-small cell lung cancer treated with erlotinib, but not in patients treated with sorafenib.

Conclusions

Our results demonstrate that the underlying biology of genes regulated by DNA methylation may have predictive value in lung cancer that can be exploited therapeutically.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-1079) contains supplementary material, which is available to authorized users.     

Polygenic in vivo validation of cancer mutations using transposons

The in vivo validation of cancer mutations and genes identified in cancer genomics is resource-intensive because of the low throughput of animal experiments. We describe a mouse model that allows multiple cancer mutations to be validated in each animal line. Animal lines are generated with multiple candidate cancer mutations using transposons. The candidate cancer genes are tagged and randomly expressed in somatic cells, allowing easy identification of the cancer genes involved in the generated tumours. This system presents a useful, generalised and efficient means for animal validation of cancer genes.

Electronic supplementary material

The online version of this article (doi:10.1186/s13059-014-0455-6) contains supplementary material, which is available to authorized users.     

Similar Source of Differential Blood mRNAs in Lung Cancer and Pulmonary Inflammatory Diseases: Calls for Improved Strategy for Identifying Cancer-Specific Biomarkers

Background

Many studies try to identify cancer diagnostic biomarkers by comparing peripheral whole blood (PWB) of cancer samples and healthy controls, explicitly or implicitly assuming that such biomarkers are potential candidate biomarkers for distinguishing cancer from nonmalignant inflammation-associated diseases.

Methods

Multiple PWB gene expression profiles for lung cancer/inflammation-associated pulmonary diseases were used for differential mRNAs identification and comparison and for proportion estimation of PWB cell subtypes.

Results

The differentially expressed genes (DE genes) between lung cancer/inflammation-associated pulmonary patients and healthy controls were reproducibly identified in different datasets. For these DE genes observed in lung cancer/inflammation-associated pulmonary diseases, more than 90.2% were differentially expressed between myeloid cells and lymphoid cells, with at least 96.8% having consistent directions of regulation (up- or down-regulations) in myeloid cells compared to lymphoid cells, explainable by the shifted populations of PWB cell subtypes under the disease conditions. The comparison of DE genes for lung cancer and inflammation-associated pulmonary diseases showed that the overlapping genes were 100% consistent in the sense of direction of regulation.

Conclusions

The differential blood mRNAs observed in lung cancer and in inflammation-associated pulmonary diseases were similar, both mainly reflecting the difference between myeloid cells and lymphoid cells predominantly determined by PWB cell population shifts. Thus, the strategy of comparing cancer with healthy controls may provide little information of the ability of the identified candidate biomarkers in discriminating cancer from inflammation-associated pulmonary diseases.     

Integration of DNA copy number alterations and transcriptional expression analysis in human gastric cancer

Background

Genomic instability with frequent DNA copy number alterations is one of the key hallmarks of carcinogenesis. The chromosomal regions with frequent DNA copy number gain and loss in human gastric cancer are still poorly defined. It remains unknown how the DNA copy number variations contributes to the changes of gene expression profiles, especially on the global level.

Principal Findings

We analyzed DNA copy number alterations in 64 human gastric cancer samples and 8 gastric cancer cell lines using bacterial artificial chromosome (BAC) arrays based comparative genomic hybridization (aCGH). Statistical analysis was applied to correlate previously published gene expression data obtained from cDNA microarrays with corresponding DNA copy number variation data to identify candidate oncogenes and tumor suppressor genes. We found that gastric cancer samples showed recurrent DNA copy number variations, including gains at 5p, 8q, 20p, 20q, and losses at 4q, 9p, 18q, 21q. The most frequent regions of amplification were 20q12 (7/72), 20q12–20q13.1 (12/72), 20q13.1–20q13.2 (11/72) and 20q13.2–20q13.3 (6/72). The most frequent deleted region was 9p21 (8/72). Correlating gene expression array data with aCGH identified 321 candidate oncogenes, which were overexpressed and showed frequent DNA copy number gains; and 12 candidate tumor suppressor genes which were down-regulated and showed frequent DNA copy number losses in human gastric cancers. Three networks of significantly expressed genes in gastric cancer samples were identified by ingenuity pathway analysis.

Conclusions

This study provides insight into DNA copy number variations and their contribution to altered gene expression profiles during human gastric cancer development. It provides novel candidate driver oncogenes or tumor suppressor genes for human gastric cancer, useful pathway maps for the future understanding of the molecular pathogenesis of this malignancy, and the construction of new therapeutic targets.     

Construction of preferential cDNA microarray specialized for human colorectal carcinoma: molecular sketch of colorectal cancer

cDNA microarray analyses can be used to identify candidate genes that play important roles in human carcinogenesis. To gain insight into the molecular sketch of colorectal cancer, we have constructed cDNA microarrays specialized for colorectal cancer, which we named "Colonochip" by selecting genes that are expressed in colorectal cancer, normal colonic mucosa, and liver metastatic cancer tissues. This microarray contained 4608 nonredundant cDNA clones from over 30,000 cDNA clones derived from the three types of human cDNA libraries, as well as clones from 170 additional conventional major genes suspected to be involved in colorectal carcinogenesis, according to literatures. Using this "Colonochip," we were able to identify 59 genes showing twofold or more differential expression between primary cancer and normal colonic mucosa, potent candidates for diagnosis, and therapy of colorectal cancer for further studies.     

The identification of six risk genes for ovarian cancer platinum response based on global network algorithm and verification analysis

Ovarian cancer is the most lethal gynaecological cancer, and resistance of platinum‐based chemotherapy is the main reason for treatment failure. The aim of the present study was to identify candidate genes involved in ovarian cancer platinum response by analysing genes from homologous recombination and Fanconi anaemia pathways. Associations between these two functional genes were explored in the study, and we performed a random walk algorithm based on reconstructed gene‐gene network, including protein‐protein interaction and co‐expression relations. Following the random walk, all genes were ranked and GSEA analysis showed that the biological functions focused primarily on autophagy, histone modification and gluconeogenesis. Based on three types of seed nodes, the top two genes were utilized as examples. We selected a total of six candidate genes (FANCA, FANCG, POLD1, KDM1A, BLM and BRCA1) for subsequent verification. The validation results of the six candidate genes have significance in three independent ovarian cancer data sets with platinum‐resistant and platinum‐sensitive information. To explore the correlation between biomarkers and clinical prognostic factors, we performed differential analysis and multivariate clinical subgroup analysis for six candidate genes at both mRNA and protein levels. And each of the six candidate genes and their neighbouring genes with a mutation rate greater than 10% were also analysed by network construction and functional enrichment analysis. In the meanwhile, the survival analysis for platinum‐treated patients was performed in the current study. Finally, the RT‐qPCR assay was used to determine the performance of candidate genes in ovarian cancer platinum response. Taken together, this research demonstrated that comprehensive bioinformatics methods could help to understand the molecular mechanism of platinum response and provide new strategies for overcoming platinum resistance in ovarian cancer treatment.