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PubMed2005

Expression profile of malignant and non-malignant diseases of the thyroid gland reveals altered expression of a common set of genes in goiter and papillary carcinomas.

Using cDNA microarrays with 3800 cDNA fragments, we determined the expression profile of normal thyroid tissue, goiter, adenoma and papillary carcinoma (10 samples from each class). After background correction and statistical analysis, we identified a set of 160 genes as being differentially expressed in all pair-wise comparisons. Here we demonstrate that, at least on the basis of these differentially expressed genes, a positive correlation between goiter and papillary carcinomas could be observed. We identified a common set of genes whose expression is diminished in both goiter and papillary carcinomas as compared to normal thyroid tissue. Moreover, no genes with inverse correlation in samples from goiter and papillary carcinomas could be detected. Using Real-Time PCR and/or tissue microarrays, we confirmed the altered expression of some of the identified genes. Of notice, we demonstrate that the reduced mRNA levels of p27(kip1) observed in papillary carcinomas as compared to either goiter or normal thyroid tissues (P<0.001) is accompanied by an altered protein distribution within the cell. In papillary carcinomas, P27(KIP1) is preferentially cytoplasmic as opposed to goiter or normal thyroid tissue, where P27(KIP1) is preferentially located in the nucleus. The exploitation of the data presented here could contribute to the understanding of the molecular events related to thyroid diseases and gives support to the notion that common molecular events might be related to the frequent observation of areas of papillary carcinomas in the gland of patients with goiter.

Carcinoma, Papillary↗

PubMed2006

Multiple gene expression analyses in paraffin-embedded tissues by TaqMan low-density array: Application to hedgehog and Wnt pathway analysis in ovarian endometrioid adenocarcinoma.

Recent studies have shown the hedgehog and Wnt families of signaling proteins to be associated with tumor initiation, growth, and survival. However, these pathways remain unexplored in ovarian endometrioid adenocarcinoma (OEA). Here, we describe a novel TaqMan low-density array to examine the expression of 26 and 20 genes in the hedgehog and Wnt pathways, respectively, in six matched snap-frozen and formalin-fixed, paraffin-embedded (FPE) OEA specimens. Expression values were normalized to uninvolved ovarian epithelium. Gene expression in matched frozen and FPE tissues demonstrated significant concordance (r = 0.92, P < 0.0001). However, comparison of amplified and unamplified RNA from frozen OEA tissues revealed an altered molecular profile in amplified RNA. Amplification of RNA from FPE tissues was not successful. The expression of Desert hedgehog (DHH), Indian hedgehog (IHH), Hedge-hog interacting protein (HHIP), Wnt10B, Wnt9B, and Wnt inhibitory factor (WIF1) were tumor-specific with no detectable expression in normal ovarian epithelium. In addition, several genes were significantly (P < 0.025) down-regulated in OEA, including cyclin E2, Porcupine, c-Myc, and Axin 2 (4.8-, 3.6-, 2.9-, and 1.9-fold, respectively). TaqMan low-density array provides an effective multivariate technique for examining gene expression in RNA isolated from either snap-frozen or archival FPE tissues and can identify tumor-specific genes, possibly leading to novel treatments.

Animals↗

PubMed2003

Differential gene expression in leiomyosarcoma.

BACKGROUND: Leiomyosarcomas (LMS) are a common subtype of soft tissue sarcoma. The molecular causes of the disease remain unclear. METHODS: In the current study, gene expression in LMS, leiomyomas, and normal myometrium was examined. RNA was prepared and gene expression was determined using microarray analysis arrays containing approximately 12,000 known genes and 48,000 expressed sequence tags (ESTs). RESULTS: A number of genes were found to be differentially expressed in these sample sets, and six genes including cyclin-dependent kinase inhibitor 2A, diaphanous (Drosophila homolog) 3, doublecortin, calpain 6, interleukin-17B, and proteolipid 1 were found to be overexpressed in LMS compared with normal myometrium and 18 other tissues. Sets of genes were identified whose expression could be used to cluster samples with either LMS, leiomyomas, or normal myometrium. CONCLUSIONS: The authors concluded that differences in gene expression can be detected between LMS and leiomyomas, normal myometrium, and other tissues, and that these changes in gene expression may yield clues with regard to the pathophysiology of leiomyosarcoma.

Adult↗

PubMed2003

Revisiting ubiquity and tissue specificity of human calpains.

The abundance of mRNAs transcribed from human genes of the calpain superfamily was studied in 72 human tissues and cell types by the Human Multiple Tissue Expression (MTE) Array technique. The analysis included the large subunits of mu- and m-calpains, the small subunits, calpastatin and calpain 3 (p94). Besides specific data on transcriptional activity, two major conclusions emerged: (i) 'ubiquitous' calpains are not expressed in all cell types, and (ii) a 'tissue-specific' calpain may be expressed in many cell types apart from the one in which it is particularly abundant. Therefore, the categoric classification of 'ubiquitous' vs. 'tissue-specific' calpains is a simplification.

Calcium-Binding Proteins↗

PubMed2004

Post-genomic applications of tissue microarrays: basic research, prognostic oncology, clinical genomics and drug discovery.

Tissue microarrays (TMAs) are an ordered array of tissue cores on a glass slide. They permit immunohistochemical analysis of numerous tissue sections under identical experimental conditions. The arrays can contain samples of every organ in the human body, or a wide variety of common tumors and obscure clinical cases alongside normal controls. The arrays can also contain pellets of cultured tumor cell lines. These arrays may be used like any histological section for immunohistochemistry and in situ hybridization to detect protein and gene expression. This new technology will allow investigators to analyze numerous biomarkers over essentially identical samples, develop novel prognostic markers and validate potential drug targets. The ability to combine TMA technology with DNA microarrays and proteomics makes it a very attractive tool for analysis of gene expression in clinically stratified tumor specimens and relate expression of each particular protein with clinical outcome. Public domain software allows researchers to examine digital images of individual histological specimens from TMAs, evaluate and score them and store the quantitative data in a relational database. TMA technology may be specifically applied to the profiling of proteins of interest in other pathophysiological conditions such as congestive heart failure, renal disease, hypertension, diabetes, cystic fibrosis and neurodegenerative disorders. This review is intended to summarize the strengths and weaknesses of TMA technology which will have an increasingly important role in the laboratories of the post-genomic era.

Animals↗

PubMed2006

Identification of novel brain biomarkers.

BACKGROUND: The diagnosis of diseases leading to brain injury, such as stroke, Alzheimer disease, and Parkinson disease, can often be problematic. In this study, we pursued the discovery of biomarkers that might be specific and sensitive to brain injury. METHODS: We performed gene array analyses on a mouse model to look for biomarkers that are both preferentially and abundantly produced in the brain. Via bioinformatics databases, we identified the human homologs of genes that appeared abundant in brain but not in other tissues. We then confirmed protein production of the genes via Western blot of various tissue homogenates and assayed for one of the markers, visinin-like protein 1 (VLP-1), in plasma from patients after ischemic stroke. RESULTS: Twenty-nine genes that were preferentially and abundantly expressed in the mouse brain were identified; of these 29 genes, 26 had human homologs. We focused on 17 of these genes and their protein products on the basis of their molecular characteristics, novelty, and/or availability of antibodies. Western blot showed strong signals in brain homogenates for 13 of these proteins. Tissue specificity was tested by Western blot on a human tissue array, and a sensitive and quantitative sandwich immunoassay was developed for the most abundant gene product observed in our search, VLP-1. VLP-1 was detected in plasma of patients after stroke and in cerebrospinal fluid of a rat model of stroke. CONCLUSIONS: The use of relative mRNA production appears to be a valid method of identifying possible biomarkers of tissue injury. The tissue specificity suggested by gene expression was confirmed by Western blot. One of the biomarkers identified, VLP-1, was increased in a rat model of stroke and in plasma of patients after stroke. More extensive, prospective studies of the candidate biomarkers identified appear warranted.

Animals↗

PubMed2006

Early gene expression profile in mouse brain after exposure to ionizing radiation.

Acute changes in the gene expression profile in mouse brain after exposure to ionizing radiation were studied using microarray analysis. RNA was isolated at 0.25, 1, 5 and 24 h after exposure to 20 Gy and at 5 h after exposure of the whole brain of adult mice to 2 or 10 Gy. RNA was hybridized onto 15K cDNA microarrays, and data were analyzed using GeneSpring and Significant Analysis of Microarray. Radiation modulated the expression of 128, 334, 325 and 155 genes and ESTs at 0.25, 1, 5 and 24 h after 20 Gy and 60 and 168 at 5 h after 2 and 10 Gy, respectively. The expression profiles showed dose- and time-dependent changes in both expression levels and numbers of differentially modulated genes and ESTs. Seventy-eight genes were modulated at two or more times. Differentially modulated genes were associated with 12 different classes of molecular function and 24 different biological pathways and showed time- and dose-dependent changes. The change in expression of four genes (Jak3, Dffb, Nsep1 and Terf1) after irradiation was validated using quantitative real-time PCR. Up-regulation of Jak3 was observed in another mouse strain. In mouse brain, there was an increase of Jak3 immunoreactivity after irradiation. In conclusion, changes in the gene profile in the brain after irradiation are complex and are dependent on time and dose, and genes with diverse functions and pathways are modulated.

Animals↗

PubMed2004

Clinicopathologic analysis of esophageal and cardiac cancers and survey of molecular expression on tissue arrays in Chaoshan littoral of China.

AIM: To investigate clinical and pathologic data of esophageal carcinoma (EC) and cardiac carcinoma (CC) among residents in Chaoshan region of China. METHODS: Clinical and pathologic data of 9 650 patients with EC and 4 173 patients with CC in the Chaoshan population were collected and analyzed. Moreover, Chaoshan esophageal carcinoma tissue arrays were made for high-throughput study. RESULTS: Male to female ratio was 3:1 in patients with EC and 4.75:1 in CC. The average age of the occurrence of EC was 54.6 years, and of CC was 58.1 years. For both EC and CC, age at diagnosis was a little younger in Chaoshan region than in most other areas. The most commonly affected site of esophageal carcinoma was the middle third of esophagus (72.0%); the second was the lower third (15.3%). The main gross type of esophageal carcinoma was ulcerative type (41.50%); the medullary type was the second (39.6%). Squamous cell carcinoma accounted for the overwhelming majority of esophageal cancer (96.4%); adenocarcinoma accounted for the overwhelming majority of cardiac carcinoma (94.5%). Chaoshan esophageal carcinoma tissue arrays were easily for high-throughput study, and tissue cores with a diameter of 1.5 mm could better keep more structure for molecular expression study. CONCLUSION: Both EC and CC are common in males. The average occurrence age of EC and CC is younger in Chaoshan than in most other regions of China. The most commonly affected site of esophageal carcinoma was the middle third of esophagus (72.0%). Squamous cell carcinoma accounted for the overwhelming majority of esophageal cancer; adenocarcinoma accounted for the overwhelming majority of cardiac carcinoma. Tissue arrays technology is applicable for rapid molecular profiling of large numbers of cancers in a single experiment.

Adolescent↗

PubMed2003

Modulation of human luteinizing hormone beta gene transcription by MIP-2A.

MIP-2A was recently identified as a MBP-1 interacting cellular protein. We have shown previously that MBP-1 acts as a transcriptional repressor. Functional association between MIP-2A and MBP-1 suggests that MIP-2A can act as a cofactor and relieves MBP-1-mediated transcriptional repression. In this study, we report the tissue-specific expression of MIP-2A and its role in the regulation of gene transcription. RNA dot blot analysis of human multiple tissue expression array suggested that MIP-2A is highly abundant in right cerebellum, pituitary, adrenal, and testis but barely detectable in skeletal muscle. Predominant expression of MIP-2A in pituitary tissue led us to investigate whether MIP-2A can transcriptionally regulate luteinizing hormone beta (LHbeta), a pituitary-specific hormone synthesized and secreted from gonadotropic cells. The LHbeta promoter is regulated by the orphan nuclear receptor SF-1 and homeodomain protein Ptx1. Although each factor enhances the LHbeta promoter, coexpression of both results in a strong synergistic activation. Therefore, we examined whether MIP-2A can modulate SF-1- and Ptx1-mediated transcriptional activation. Our results suggested that MIP-2A expression inhibits SF-1- and Ptx1-mediated transactivation of LHbeta promoter. Subsequent analysis demonstrated that MIP-2A physically interacts with both SF-1 and Ptx1, thereby inhibiting transactivation of the LHbeta promoter. Taken together, our results indicate that MIP-2A preferentially expresses in certain tissues, including the pituitary gland, and negatively regulates the LHbeta gene transcription.

Binding Sites↗

PubMed2006

ADAM15 disintegrin is associated with aggressive prostate and breast cancer disease.

The aim of the current study was to evaluate the expression of ADAM15 disintegrin (ADAM15) in a broad spectrum of human tumors. The transcript for ADAM15 was found to be highly upregulated in a variety of tumor cDNA expression arrays. ADAM15 protein expression was examined in tissue microarrays (TMAs) consisting of 638 tissue cores. TMA analysis revealed that ADAM15 protein was significantly increased in multiple types of adenocarcinoma, specifically in prostate and breast cancer specimens. Statistical association was observed with disease progression within clinical parameters of predictive outcome for both prostate and breast cancers, pertaining to Gleason sum and angioinvasion, respectively. In this report, we also present data from a cDNA microarray of prostate cancer (PCa), where we compared transfected LNCaP cells that overexpress ADAM15 to vector control cells. In these experiments, we found that ADAM15 expression was associated with the induction of specific proteases and protease inhibitors, particularly tissue inhibitor of metalloproteinase 2, as validated in a separate PCa TMA. These results suggest that ADAM15 is generally overexpressed in adenocarcinoma and is highly associated with metastatic progression of prostate and breast cancers.

ADAM Proteins↗

PubMed2002

High pressure effects on cellular expression profile and mRNA stability. A cDNA array analysis.

Hydrostatic pressure has a profound effect on cartilage tissue and chondrocyte metabolism. Depending on the type and magnitude of pressure various responses can occur in the cells. The mechanisms of mechanotransduction at cellular level and the events leading to specific changes in gene expression are still poorly understood. We have previously shown that induction of stress response in immortalized chondrocytes exposed to high static hydrostatic pressure increases the stability of heat shock protein 70 mRNA. In this study, our aim was to examine the effect of high pressure on gene expression profile and to study whether stabilization of mRNA molecules is a general phenomenon under this condition. For this purpose a cDNA array analysis was used to compare mRNA expression profile in pressurized vs. non-pressurized human chondrosarcoma cells (HCS 2/8). mRNA stability was analyzed using actinomycin-treated and nontreated samples collected after pressure treatment. A number of immediate-early genes, and genes regulating cell cycle and growth were up-regulated due to high pressure. Decrease in osteonectin, fibronectin, and collagen types VI and XVI mRNAs was observed. Also bikunin, cdc37 homologue and Tiam1, genes linked with hyaluronan metabolism, were down-regulated. In general, stability of down-regulated mRNA species appeared to increase. However, no increase in mRNA above control level due to stabilization was noticed in the genes available in the array. On the other hand, mRNAs of certain immediate-early genes, like c-jun, jun-B and c-myc, became destabilized under pressure treatment. Increased accumulation of mRNA on account of stabilization under high pressure conditions seems to be a tightly regulated, specific phenomenon.

Cartilage, Articular↗

PubMed2006

Cytogenetic analysis of myxoid liposarcoma and myxofibrosarcoma by array-based comparative genomic hybridisation.

AIM: To investigate overall chromosomal alterations using array-based comparative genomic hybridisation (CGH) of myxoid liposarcomas (MLSs) and myxofibrosarcomas (MFSs). MATERIALS AND METHODS: Genomic DNA extracted from fresh-frozen tumour tissues was labelled with fluorochromes and then hybridised on to an array consisting of 1440 bacterial artificial chromosome clones representing regions throughout the entire human genome important in cytogenetics and oncology. RESULTS: DNA copy number aberrations (CNAs) were found in all the 8 MFSs, but no alterations were found in 7 (70%) of 10 MLSs. In MFSs, the most frequent CNAs were gains at 7p21.1-p22.1 and 12q15-q21.1 and a loss at 13q14.3-q34. The second most frequent CNAs were gains at 7q33-q35, 9q22.31-q22.33, 12p13.32-pter, 17q22-q23, Xp11.2 and Xq12 and losses at 10p13-p14, 10q25, 11p11-p14, 11q23.3-q25, 20p11-p12 and 21q22.13-q22.2, which were detected in 38% of the MFSs examined. In MLSs, only a few CNAs were found in two sarcomas with gains at 8p21.2-p23.3, 8q11.22-q12.2 and 8q23.1-q24.3, and in one with gains at 5p13.2-p14.3 and 5q11.2-5q35.2 and a loss at 21q22.2-qter. CONCLUSIONS: MFS has more frequent and diverse CNAs than MLS, which reinforces the hypothesis that MFS is genetically different from MLS. Out-array CGH analysis may also provide several entry points for the identification of candidate genes associated with oncogenesis and progression in MFS.

Adult↗

PubMed2002

Global and hormone-induced gene expression changes during shoot development in Arabidopsis.

A global analysis of gene expression events during shoot development in Arabidopsis was conducted using oligonucleotide array analysis. Shoots can be induced in tissue culture by preincubating root explants on an auxin-rich callus induction medium (CIM) and by transferring explants to a cytokinin-rich shoot induction medium (SIM), during which time explants become committed to shoot formation and ultimately form shoots. Oligonucleotide array data obtained during shoot development from approximately 8000 Arabidopsis genes were subjected to principal component analysis, which demonstrated that the major components of variation in gene expression during shoot development can be represented by groups of genes, each group of which is upregulated at only one developmental stage. Two percent to three percent of the approximately 8000 Arabidopsis genes monitored in this study were upregulated by fourfold or more at any one stage during shoot development. When upregulated and downregulated genes were categorized by function, it was observed that numerous hormone response genes were upregulated during preincubation on CIM. Groups of genes involved in signaling and/or transcription were induced at or before the time of shoot commitment, and genes that encode components of the photosynthetic apparatus were upregulated later in development before shoot emergence. Primary hormone response genes, such as Aux/IAA genes, were upregulated during preincubation on auxin-rich CIM, and cytokinin-responsive response regulator genes were upregulated during incubation on cytokinin-rich SIM. The expression of ARABIDOPSIS RESPONSE REGULATOR5, a type-A response regulator gene, was upregulated at the time of shoot commitment, and its expression was localized to sites of presumptive shoot formation. Two "hybrid" His kinases involved in cytokinin responses, CRE1, which encodes a cytokinin receptor, and CKI1, a gene that is capable of conferring cytokinin-independent shoot development, were upregulated during incubation on SIM.

Arabidopsis↗

PubMed2003

Gene expression analysis of human middle ear cholesteatoma using complementary DNA arrays.

OBJECTIVE: To identify genes regulated in human cholesteatoma compared with normal skin tissue using complementary DNA arrays. STUDY DESIGN: In vitro analysis. METHODS: Eight cholesteatoma and retroauricular skin samples were obtained from the same patients during surgery. Upregulated and downregulated genes were highlighted using complementary DNA arrays for screening. Reverse transcriptase-polymerase chain reaction and immunohistochemical staining were performed to confirm the results of the complementary DNA array. RESULTS: Twelve genes were found to be induced or upregulated in cholesteatoma compared with skin samples. These included genes involved in cell proliferation and differentiation (eg, calgranulin A, calgranulin B, psoriasin, thymosin beta-10) and cell invasion (eg, cathepsin C, cathepsin D, cathepsin H). Analyses by means of reverse transcription-polymerase chain reaction showed enhanced expression of several genes including calgranulin A, calgranulin B, psoriasin, thymosin beta-10, cathepsin C, cathepsin D, and cathepsin H in cholesteatoma, supporting the findings from the gene array. In addition, it was verified by immunohistochemical analysis that the expressions of Calgranulin A, Calgranulin B, and Cathepsin D were mainly located in cholesteatoma epithelium. CONCLUSION: The observed alteration in gene expression may play a role in various mechanisms of pathogenesis in cholesteatoma.

Actins↗

PubMed2004

Design, construction, and use of tissue microarrays.

Tissue microarrays are a platform for high-throughput analysis of tissue specimens in research. They are used for target verification of results from complementary deoxyribonucleic acid (cDNA) microarrays, expression profiling of tumors and tissues, as well as in epidemiology-based investigations. Tissue microarrays are a simple reagent that can be constructed from archival paraffin-embedded tissue for immunohistochemical staining, in situ hybridization, and other methodologies. The design and precision in execution of a tissue microarray is essential to obtain the desired results. Tissue microarrays are a powerful proteomic platform for research.

Animals↗

PubMed2004

Molecular profiling of mouse lung tumors: association with tumor progression, lung development, and human lung adenocarcinomas.

We have performed oligonucleotide array analysis on various murine lung tissues [normal lungs, lung adenomas, and lung adenocarcinomas (ACs)] using Affymetrix U74Av2 GeneChips to examine the complex genetic changes occurring during lung carcinogenesis. Analysis yielded 20 novel genes differentially expressed in both lung adenomas and ACs versus normal lungs, including the tumor suppressor APC2 and the oncogene Ros 1. In addition, 50 genes were found to be differentially expressed in lung adenomas versus lung ACs, including the differentiation factor Hox C6, the oncogene Ets 2, and the Ras nuclear transport factor, nuclear transport factor 2. To understand the potential relationship between genes expressed in murine lung tumors and its relationship to altered gene expression observed during embryogenesis and postnatal development, tissues from embryonic lungs and from lungs of mice up to 4 weeks following birth were examined using Affymetrix U74Av2 GeneChips. From this analysis, approximately 1300 genes were determined to exhibit differential expression in fetal lung versus postnatal lung. When we compared lung adenomas, lung ACs, and normal lung parenchyma, 24 developmentally regulated genes were found aberrantly expressed in lung tumors; these included the cell cycle control factor CDC5, the cellular differentiation factor TEA domain 4, and the proapoptotic factor BNIP 2. Finally, we compared the murine lung tumor gene expression data to the expression of genes in human lung cancer, in order to assess the relevance of murine lung cancer models in the study of human AC formation. When the 17 human lung ACs and six human lung large cell carcinomas were examined, it was found that 13 of the 17 human lung ACs clustered tightly together in a pattern that was different from the remaining four human lung ACs and six large cell carcinomas, which exhibited a different pattern. Interestingly, the mouse lung adenomas appeared similar to 13 clustered ACs, while mouse lung ACs appeared more similar in pattern to the group consisting of four ACs and six large-cell carcinomas (LCCs). Nevertheless, when compared with the combined human ACs, 39 genes with similar expression changes in murine lung tumors and human ACs/LCCs were identified, such as the oncogene-related BCL7B, the cell cycle regulator CDK4, and the proapoptotic Endophilin B1. Overall, we have determined, for the first time, the expression profiles during murine lung tumor progression and have established, at the molecular level, an association between murine lung tumorigenesis and lung development. We have also attempted to compare the expression profiles found in mouse lung cancers and those in human lung ACs.

Adenocarcinoma↗

PubMed2004

Deciphering a subgroup of breast carcinomas with putative progression of grade during carcinogenesis revealed by comparative genomic hybridisation (CGH) and immunohistochemistry.

Distinct parallel cytogenetic pathways in breast carcinogenesis could be identified in recent years. Nevertheless, it remained unclear as to which tumours may have progressed in grade or which patterns of cytogenetic alteration may define the switch from an in situ towards an invasive lesion. In order to gain more detailed insights into cytogenetic mechanisms of the pathogenesis of breast cancer, the chromosomal imbalances of 206 invasive breast cancer cases were characterised by means of comparative genomic hybridisation (CGH). CGH data were subjected to hierarchical cluster analysis and the results were further compared with immunohistochemical findings on tissue arrays from the same breast cancer cases. The combined analysis of immunohistochemical and cytogenetic data provided evidence that carcinomas with gains of 7p, and to a lesser extent losses of 9q and gains of 5p, are a distinct subgroup within the spectrum of ductal invasive grade 3 breast carcinomas. These aberrations were associated with a high degree of cytogenetic instability (16.6 alterations per case on average), 16q-losses in over 70% of these cases, strong oestrogen receptor expression and absence of strong expression of p53, c-erbB2 and Ck 5. These characteristics provide strong support for the hypothesis that these tumours may develop through stages of well- and perhaps intermediately differentiated breast cancers. Our results therefore underline the existence of several parallel and also stepwise progression pathways towards breast cancer.

Breast Neoplasms↗

PubMed1999

Gene expression relevant to Down syndrome: problems and approaches.

The long arm of human chromosome 21 likely contains several hundred genes. To determine which of these are responsible for specific aspects of the Down Syndrome phenotype, protein functional analysis coupled to phenotypic analysis of transgenic mice will be required. Because such experiments are both time consuming and expensive, prioritizing 21q genes for further studies would be advantageous. Here, we discuss expression analysis, specifically the use of Northern analysis, cDNA array screening and RNA tissue in situ hybridization to assess place and time of expression of forty-two genes. For a subset of these, over expression in normal versus trisomy cell lines and mouse tissues is discussed. Lastly, several examples of alternative processing and their potential for generation of brain specific proteins are described. Together, these experiments give information on time, place and level of expression of a number of 21q genes and suggest some interesting candidates worth further investigation for relevance to Down Syndrome. These data also illustrate the complexities and ambiguities inherent in interpretation and use of expression information.

Adult↗