Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Genomic profiling”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources
PubMed2004

Fetal cell carcinogenesis of the thyroid: a hypothesis for better understanding of gene expression profile and genomic alternation in thyroid carcinoma.

Since the 1980s, cancer cells have been considered to be generated from well-differentiated benign cells by transformation caused by accumulating damage in their genomes. However, recent progress in gene expression analysis in thyroid malignancies has raised the possibility of another model of thyroid carcinogenesis. We propose a novel hypothesis of thyroid carcinogenesis, the fetal cell carcinogenesis hypothesis, in which cancer cells are derived from the remnants of fetal thyroid cells, instead of from normal thyroid follicular cells. This hypothesis explains well the clinical and biological features and recent molecular evidence of thyroid carcinoma. It suggests the importance of clarifying the molecular mechanism of thyroid development and the identification of fetal thyroid cells such as thyroid stem cells (TSCs), since such data will lead to a better understanding of thyroid carcinogenesis and thyroid regeneration.

Carcinoma, Papillary, Follicular↗
PubMed2026

Long-Term Outcomes and Paired Immune and Genomic Exploratory Analyses After Neoadjuvant Dose-Dense MVAC in Muscle-Invasive Bladder Cancer: A Single-Centre Case Series.

Background/Objectives: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy has been the standard of care for muscle-invasive bladder cancer (MIBC) for two decades, yet a substantial proportion of patients derive no benefit. As antibody-drug conjugates and immune checkpoint inhibitors reshape perioperative treatment, it is unclear which patients retain meaningful benefit from platinum. We describe long-term outcomes and exploratory paired immune and genomic analyses in a single-centre cohort treated with dose-dense MVAC (dd-MVAC). Methods: We retrospectively identified 54 consecutive patients with MIBC treated with neoadjuvant dd-MVAC between November 2013 and November 2019. Forty-two underwent radical cystectomy and are assessable for pathologic response. Immunohistochemistry for CD3, CD8, FOXP3, PD-1, PD-L1, PD-L2, and NY-ESO-1 was evaluable in 31 baseline specimens and 22 paired specimens; paired genomic profiling was evaluable in 12 cases, with paired tumour mutational burden (TMB) in 10 by whole-exome sequencing and 7 by TSO-500. Paired analyses necessarily exclude patients achieving a pathologic complete response (pCR), who have no residual tumour, and most early progressors. Results: pCR was achieved in 11/42 operated patients (26%, 95% CI 15-41). Median follow-up was 87 months (IQR 24-104). Hydronephrosis was the only baseline factor associated with absence of pCR (p = 0.016). Within the operated cohort, pCR was associated with longer recurrence-free survival (log-rank p = 0.017), but the difference in overall survival did not reach significance (p = 0.121). NAC reduced intratumoral FOXP3 (q = 0.001), NY-ESO-1 (q = 0.013), PD-L2 (q = 0.013), and CD3 (q = 0.043) after correction for multiple comparisons, whereas TMB showed no significant change (TSO-500 p = 0.67; WES p = 0.86). No statistically significant association was detected between any baseline immune marker, including PD-L1, and pCR. The mutational landscape was largely concordant before and after NAC. Conclusions: This study was exploratory and was not powered to validate predictive biomarkers. In this long-term cohort, dd-MVAC was associated with measurable depletion of intratumoral immune populations in chemoresistant tumours, while paired genomic profiles remained broadly concordant. No pre-treatment biomarker identified platinum-refractory patients, but the small evaluable subsets mean these are hypothesis-generating rather than negative findings, and prospective studies with pre-specified biomarker endpoints are required.

chemoresistance↗
PubMed2006

The temporal profile of genomic responses and protein synthesis in ischemic tolerance of the rat brain induced by repeated hyperbaric oxygen.

Repeated hyperbaric oxygen (HBO) exposure prior to ischemia has been reported to provide neuroprotection against ischemic brain injury. The present study examined the time course of neuroprotection of HBO (3.5 atmosphere absolute, 100% oxygen, 1 h for 5 consecutive days) and the changes of gene/protein expression in rats. First, at 6 h, 12 h, 24 h, and 72 h after HBO sessions, rats were subjected to forebrain ischemia (8 min). Histopathological examination of hippocampal CA1 neurons was done 7 days after ischemia. Second, temporal genomic responses and protein expression were examined at the same time points after HBO sessions without subjecting animals to ischemia. HBO significantly reduced loss of hippocampal CA1 neurons that normally follows transient forebrain ischemia when the last HBO session was 6 h, 12 h, or 24 h before ischemia (survived neurons 55%, 75%, and 53%, respectively), whereas if there was a 72-h delay before the ischemic insult, HBO was not protective (survived neurons only 6%). Statistical analysis on microarray data showed significant upregulation in 60 probe sets including 7 annotated genes (p75NTR, C/EBPdelta, CD74, Edg2, Trip10, Nrp1, and Igf2), whose time course expressions corresponded to HBO-induced neuroprotection. The protein levels of p75NTR, C/EBPdelta, and CD74 were significantly increased (maximum fold changes 2.9, 2.0, and 7.9, respectively). The results suggest that HBO-induced neuroprotection against ischemic injury has time window, protective at 6 h, 12 h and 24 h but not protective at 72 h. Although the precise interaction is to be determined, the genes/proteins relevant to neurotrophin and inflammatory-immune system may be involved in HBO-induced neuroprotection.

Animals↗
PubMed2026

PSIP1::TBL1X: a recurrent gene fusion in pancreatic neuroendocrine tumors.

Effective treatment of metastatic neuroendocrine tumors (NETs) is limited by a lack of targeted therapies and clinically useful predictive biomarkers. We applied complementary genomic profiling technologies, including optical genome mapping (OGM) and whole exome sequencing (WES), to 70 liver metastases of NETs from multiple anatomical primary sites to identify actionable genomic alterations. We detected recurrent fusions involving TBL1X (PSIP1::TBL1X) and BEND2 (CHD7::BEND2 and NEO1::BEND2) by OGM in pancreatic neuroendocrine tumors (pNETs). The expression of the PSIP1::TBL1X fusion was confirmed by PacBio Iso-Seq long-read transcriptome sequencing and nested rtPCR, and fusion protein expression was established by western blotting. Expression of the PSIP1::TBL1X fusion was also assayed in a separate cohort of 31 specimens from 28 pNET cases by rtPCR. Across both cohorts, PSIP1::TBL1X was identified in 11% of pNET patients with available metastatic tissue, but was not detected in primary tumor specimens. All PSIP1::TBL1X fusion isoforms were found to retain early exons of PSIP1 and the complete coding sequence of TBL1X. Consistent with prior reports, BEND2 fusions were associated with high-grade tumors and may represent a clinically useful biomarker for aggressive disease. Notably, TBL1X and BEND2 fusions did not co-occur with ATRX/DAXX mutations, defining a distinct molecular subgroup of pNETs. This study highlights the importance of structural variant profiling in molecular profiling studies and supports a revised view of the role of gene fusions in neuroendocrine malignancies.

Humans↗
PubMed2000

Genomic HLA profiles of MS in Hokkaido, Japan: important role of DPB1*0501 allele.

The polymorphism of the HLA class II genes was investigated in 97 patients with multiple sclerosis (MS) in Hokkaido, the northernmost main island of Japan. Of these, 80 patients were classified as having conventional MS and 17 as having opticospinal MS (OS-MS). Our findings confirmed a previous report that the DPB 1*0501 allele is positively associated with OS-MS (P = 0.0043). The frequency of DPB 1*0501 was also found to be higher in conventional MS patients than in controls (79% vs. 58%, P = 0.0084), although the differences were not statistically significant. Our results indicate that OS-MS is a DPB 1*0501-associated subgroup of MS, and that DPB1*0501 is also correlated with risk of conventional MS in Japanese.

Adolescent↗
PubMed2000

cDNA cloning, expression profile, and genomic structure of human and mouse RNF10/Rnf 10 genes, encoding a novel RING finger protein.

RING finger (C3HC4-type zinc finger) is a variant zinc finger motif present in a new family of proteins including transcription regulators. A new member of the RING finger protein family was identified through a mouse expressed sequence tag (EST) database search, and its full-length cDNA was isolated from a mouse brain full length-enriched cDNA library. The gene was designated as Rnf10, for RING finger protein 10. The cDNA clone consists of 3110 nucleotides and encodes an open reading frame (ORF) of an 804-amino acid protein. A database search revealed that human KIAA0262 protein (accession number, D87451) has strong homology to mouse Rnf10. To confirm that mouse Rnf10 is the homolog or an isolog of human KIAA0262, a human RNF10 cDNA was cloned in our hands from a fetal brain cDNA pool. The newly isolated cDNA contained an ORF for 811 amino acids which had almost identical structure to mouse Rnf10 protein, indicating that the human ORF codes for RNF10 protein. This finding was also supported by comparative chromosome mapping in which both genes were localized in a conserved linkage homology region between mouse and human. Comparison of the RNF10 and KIAA0262 proteins revealed that both were transcribed from the same gene and that the longer RNF10 ORF would be the authentic form. The complete genomic organization of RNF10 was determined to consist of 17 exons spanning at least 40kb in the genome.

Amino Acid Sequence↗
PubMed1990

Plasmid profiles and genomic DNA restriction endonuclease patterns of 30 independent Staphylococcus lugdunensis strains.

Extrachromosomal DNA analysis and restriction endonuclease analysis of whole cellular DNA were used to characterize 30 Staphylococcus lugdunensis strains isolated from 13 different hospitals from 1977 to 1988. All the strains were susceptible to most of the antibiotics tested, including penicillin G. A single 3.2 kilobase plasmid was detected in 13 strains and one or two plasmids, ranging from 2.3 to 6.6 kilobases, were found in 7 strains. EcoRI, PstI and PvuII restriction patterns of total cellular DNA were identical for 23 isolates, indicating strong conservation of endonuclease sites in this species. One or two additional DNA bands occurred in seven isolates. Molecular markers show rather little variations between different S. lugdunensis isolates suggesting that they are closely related.

DNA Restriction Enzymes↗
PubMed2026

Multiregion profiling of genomic and transcriptional heterogeneity in head and neck squamous-cell carcinoma.

BACKGROUND: Intratumoral heterogeneity (ITH) is thought to contribute to tumour evolution and treatment resistance but its biological and clinical significance in localised head and neck squamous-cell carcinoma (HNSCC) remains incompletely understood. PATIENTS AND METHODS: In the prospective SCANDARE study, we analysed 87 patients with resectable HNSCC treated with upfront surgery. Two to five spatially distinct tumour regions per patient underwent pathological evaluation, targeted DNA sequencing, and bulk RNA sequencing. Genomic ITH (gITH) was quantified using clonal deconvolution and Shannon diversity indices, whereas transcriptional heterogeneity (tITH) was assessed using the intratumour expression distance metric. Associations between ITH, molecular features, tumour microenvironment composition, and clinical outcomes were explored using multivariable statistical models. RESULTS: Pathology-based spatial heterogeneity showed limited prognostic value. gITH was common, with 37% of tumours displaying regionally heterogeneous pathogenic variants, including spatially actionable alterations in 10% of patients. In an initial multivariable Cox model, higher gITH was associated with shorter disease-free survival. However, after Ridge-penalised modelling and bootstrap internal validation, the effect size was attenuated [corrected hazard ratio 1.42, 95% confidence interval (CI) 0.91-2.75]. The overall model retained moderate discriminative performance (optimism-corrected C-index 0.69, 95% CI 0.59-0.79). gITH was associated with tumour cellularity, reduced estimated endothelial cell infiltration, and alterations in KMT2C and PIK3CA. tITH differed according to human papillomavirus (HPV) status, with lower tITH in HPV-positive tumours, and was associated with distinct biological pathways and genomic alterations. Genomic and tITH were not correlated. CONCLUSIONS: This prospective multiregion study provides a comprehensive characterisation of genomic and tITH in localised HNSCC. Our findings highlight substantial spatial molecular diversity within primary tumours and suggest potential associations between heterogeneity, tumour biology, and clinical outcome that warrant validation in independent cohorts.

head and neck squamous-cell carcinoma (HNSCC)↗
PubMed2026

Clinically actionable genomic alterations in breast cancer brain metastases.

BACKGROUND: Breast cancer brain metastases (BCBMs) represent a critical unmet clinical need in metastatic breast cancer (MBC) and the identification of novel therapeutic targets is urgently needed in this context. In this study, we describe clinically actionable targets in BCBMs using comprehensive genomic profiling. PATIENTS AND METHODS: Genomic DNA was extracted from formalin-fixed paraffin-embedded archival BCBM samples and analyzed using the commercially available Agilent SureSelect V6 whole exome sequencing (WES) kit and an Illumina NovaSeq 6000 platform. Pathogenic alterations were classified as actionable alterations (AAs) if they met the updated MBC or tumor-agnostic ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) I or II criteria of the ESCAT scale. RESULTS: WES data from 56 BCBM samples were available [33.9% hormone receptor (HR)-negative/human epidermal growth factor receptor (HER)2-negative; 25.0% HR-positive/HER2-negative; and 38% HER2-positive]. ESCAT I/II AAs were detected in 76.8% (n = 43) of all BCBMs and the most frequently detected AAs were in genes involved in the homologous recombination repair pathway (BRCA1/BRCA2/PALB2; 53.6% overall). Biallelic inactivation of BRCA1, BRCA2, or PALB2 was observed in 19.6% of samples, with higher rates in HER2-negative BCBMs (26% in HR-negative /HER2-negative and 21% in HR-positive/HER2-negative). ESCAT I/II PIK3CA/AKT1/PTEN pathway alterations were present in 48.2% of samples and, in particular, in 50% of HR-positive/HER2-negative BCBMs. No ESR1 mutation was detected in HR-positive/HER2-negative BCBMs. The prognostic impact of previously described AAs was evaluated overall and according to breast cancer subtype. Twenty-three BCBMs (41%) were classified as HER2-positive; among these, 3 (13%) presented a hotspot PIK3CA mutation and 7 (30%) presented a PTEN deletion. Among patients with HER2-positive BCBMs, the identification of a hotspot PIK3CA mutation was significantly associated with worse prognosis. CONCLUSIONS: ESCAT I/II actionable genomic alterations are frequent in BCBMs, highlighting the potential for genomically targeted treatments in this setting.

ESCAT↗
PubMed2005

Novel genes, possibly relevant for molecular diagnosis or therapy of human rhabdomyosarcoma, detected by genomic expression profiling.

Transcriptional profiles of an alveolar rhabdomyosarcoma (RMS) and of a RMS cell line were reconstructed by a computational and statistical approach. Expression data of 29,963 genes in 11 adult human healthy tissues and in 37 tumour tissues were analysed for comparison. We identified 202 genes differentially expressed in at least one RMS sample, as compared with normal skeletal muscle. Among them, 107 resulted specifically overexpressed in RMS, but in no tumour affecting other tissues. Cluster analysis applied to expression data detected a series of genes presumably co-expressed with genes encoding known tumour markers and/or reportedly involved in genesis or development of rhabdomyosarcoma. This study succeeded in identifying a number of genes, which become candidates for in vitro study, thus facilitating discovery of novel tumour markers or targets for drug therapy.

Adult↗
PubMed2003

Molecular evolution of sensory domains in cyanobacterial chemoreceptors.

Components of the chemotaxis system encoded in multiple homologous operons were identified in five cyanobacterial genomes. Analysis of phylogenetic profiles, genomic context, domain architectures and sequence identity reveal that sensory modules of chemoreceptors that detect environmental cues are the subject of frequent domain birth and death events and have accelerated rates of sequence evolution. This fact could explain a remarkable diversity of the sensing repertoire of chemotaxis receptors in microorganisms.

Bacterial Proteins↗
PubMed2003

Genomic polymorphic profiles in an Irish population with meningococcaemia: is it possible to predict severity and outcome of disease?

Patients with meningococcal disease have increased plasma levels of proinflammatory cytokines IL-6, IL-1beta, and TNF-alpha, with higher levels associated with fatal outcome. This study investigated whether polymorphisms in genes encoding these cytokines, and in those encoding anti-inflammatory IL-10 and IL-1Ra, are associated with the outcome in patients with meningococcal disease. Seven polymorphisms were genotyped in 183 meningococcal disease patients and 389 controls. The IL-6 -174 G/G and IL-10 -1082 A/A genotypes were more frequent in nonsurvivors compared with survivors (P=0.023 IL-6, 0.25 IL-10), and in patients with severe disease compared to those with mild disease (P=0.037 IL-6, 0.0078 IL-10). An association was also found between meningococcal disease and the IL-1RN VNTR polymorphism, but no association was observed with the LTA +252, TNF -308, IL-10 -592, or IL-1B +3953 polymorphisms. We conclude that genetic variability in the IL-6, IL-10, and IL-1RN genes is associated with a poor outcome in meningococcal disease.

Adult↗
PubMed2004

Genome-scale profiling of gene expression in hepatocellular carcinoma: classification, survival prediction, and identification of therapeutic targets.

The heterogeneous nature of human hepatocellular carcinoma (HCC) has hampered both treatment and prognostic predictions. Gene expression profiles of human HCC were analyzed to define the molecular characteristics of the tumors and to test the prognostic value of the expression profiles. By applying global gene expression analyses, including unsupervised and supervised methods, 2 distinctive subclasses of HCC that were highly homogeneous for both the underlying biology and the clinical outcome were discovered. Tumors from the low survival subclass had strong cell proliferation and antiapoptosis gene expression signatures. In addition, the low survival subclass displayed higher expression of genes involved in ubiquitination and sumoylation, suggesting an etiologic involvement of these processes in accelerating the progression of HCC. Genes most strongly associated with survival were identified by using the Cox proportional hazards survival analysis. This approach identified a limited number of genes that accurately predicted the length of survival and provided new molecular insights into the pathogenesis of HCC. Future studies will evaluate potential diagnostic markers and therapeutic targets identified during the global gene expression studies. Furthermore, cross-species similarity of gene expression patterns will also allow prioritization of a long list of genes obtained from human gene expression profiling studies and focus on genes whose expression is altered during tumorigenesis in both species.

Biomarkers, Tumor↗
PubMed1993

Methylation profiles of genomic DNA of mouse developmental brain detected by restriction landmark genomic scanning (RLGS) method.

Restriction landmark genomic scanning using methylation-sensitive endonucleases (RLGS-M) is a newly developed powerful method for systematic detection of DNA methylation. Using this method, we scanned mouse brain genomic DNAs from various developmental stages to detect the transcriptionally active regions. This approach is based on the assumption that CpG methylation, particularly of CpG islands, might be associated with gene transcriptional regulation. Genomic DNAs were prepared from telencephalons of 9.5-, 13.5- and 16.5-day embryos, 1- and 10-day neonates and adults, followed by subjecting them to RLGS-M and comparing their patterns with each other or with that of the adult liver. We used NotI as a methylation-sensitive restriction enzyme and surveyed the methylation states of 2,600 NotI sites, almost of which should correspond to gene loci. Although almost all RLGS spots (98%) were present constantly at every developmental stages, only a few percent of spots reproducibly appeared and disappeared at different developmental stages of the brain (44 spots, 1.7%) and some were tissue-specific (10 spots, 0.7%). These data suggest that DNA methylation associated with gene transcription is a well-programmed event during the central nervous system (CNS) development. Thus, RLGS-M can offer a means for detecting systematically the genes in which the state of DNA methylation changes during development of the higher organism.

Animals↗
PubMed2005

luxS-dependent gene regulation in Escherichia coli K-12 revealed by genomic expression profiling.

The bacterial quorum-sensing autoinducer 2 (AI-2) has received intense interest because the gene for its synthase, luxS, is common among a large number of bacterial species. We have identified luxS-controlled genes in Escherichia coli under two different growth conditions using DNA microarrays. Twenty-three genes were affected by luxS deletion in the presence of glucose, and 63 genes were influenced by luxS deletion in the absence of glucose. Minimal overlap among these gene sets suggests the role of luxS is condition dependent. Under the latter condition, the metE gene, the lsrACDBFG operon, and the flanking genes of the lsr operon (lsrR, lsrK, tam, and yneE) were among the most significantly induced genes by luxS. The E. coli lsr operon includes an additional gene, tam, encoding an S-adenosyl-l-methionine-dependent methyltransferase. Also, lsrR and lsrK belong to the same operon, lsrRK, which is positively regulated by the cyclic AMP receptor protein and negatively regulated by LsrR. lsrK is additionally transcribed by a promoter between lsrR and lsrK. Deletion of luxS was also shown to affect genes involved in methionine biosynthesis, methyl transfer reactions, iron uptake, and utilization of carbon. It was surprising, however, that so few genes were affected by luxS deletion in this E. coli K-12 strain under these conditions. Most of the highly induced genes are related to AI-2 production and transport. These data are consistent with the function of LuxS as an important metabolic enzyme but appear not to support the role of AI-2 as a true signal molecule for E. coli W3110 under the investigated conditions.

Adaptation, Psychological↗
PubMed2004

cDNA array-CGH profiling identifies genomic alterations specific to stage and MYCN-amplification in neuroblastoma.

BACKGROUND: Recurrent non-random genomic alterations are the hallmarks of cancer and the characterization of these imbalances is critical to our understanding of tumorigenesis and cancer progression. RESULTS: We performed array-comparative genomic hybridization (A-CGH) on cDNA microarrays containing 42,000 elements in neuroblastoma (NB). We found that only two chromosomes (2p and 12q) had gene amplifications and all were in the MYCN amplified samples. There were 6 independent non-contiguous amplicons (10.4-69.4 Mb) on chromosome 2, and the largest contiguous region was 1.7 Mb bounded by NAG and an EST (clone: 757451); the smallest region was 27 Kb including an EST (clone: 241343), NCYM, and MYCN. Using a probabilistic approach to identify single copy number changes, we systemically investigated the genomic alterations occurring in Stage 1 and Stage 4 NBs with and without MYCN amplification (stage 1-, 4-, and 4+). We have not found genomic alterations universally present in all (100%) three subgroups of NBs. However we identified both common and unique patterns of genomic imbalance in NB including gain of 7q32, 17q21, 17q23-24 and loss of 3p21 were common to all three categories. Finally we confirm that the most frequent specific changes in Stage 4+ tumors were the loss of 1p36 with gain of 2p24-25 and they had fewer genomic alterations compared to either stage 1 or 4-, indicating that for this subgroup of poor risk NB requires a smaller number of genomic changes are required to develop the malignant phenotype. CONCLUSIONS: cDNA A-CGH analysis is an efficient method for the detection and characterization of amplicons. Furthermore we were able to detect single copy number changes using our probabilistic approach and identified genomic alterations specific to stage and MYCN amplification.

Cell Line, Tumor↗
PubMed2001

Visualizing associations between genome sequences and gene expression data using genome-mean expression profiles.

The combination of genome-wide expression patterns and full genome sequences offers a great opportunity to further our understanding of the mechanisms and logic of transcriptional regulation. Many methods have been described that identify sequence motifs enriched in transcription control regions of genes that share similar gene expression patterns. Here we present an alternative approach that evaluates the transcriptional information contained by specific sequence motifs by computing for each motif the mean expression profile of all genes that contain the motif in their transcription control regions. These genome-mean expression profiles (GMEP's) are valuable for visualizing the relationship between genome sequences and gene expression data, and for characterizing the transcriptional importance of specific sequence motifs. Analysis of GMEP's calculated from a dataset of 519 whole-genome microarray experiments in Saccharomyces cerevisiae show a significant correlation between GMEP's of motifs that are reverse complements, a result that supports the relationship between GMEP's and transcriptional regulation. Hierarchical clustering of GMEP's identifies clusters of motifs that correspond to binding sites of well-characterized transcription factors. The GMEP's of these clustered motifs have patterns of variation across conditions that reflect the known activities of these transcription factors. Software that computed GMEP's from sequence and gene expression data is available under the terms of the Gnu Public License from http://rana.lbl.gov/.

Algorithms↗