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Results for “Cancer genomics”

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.

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At least 73 records · Page 4Linked to original sources
PubMed2004

An integrated view of copy number and allelic alterations in the cancer genome using single nucleotide polymorphism arrays.

Changes in DNA copy number contribute to cancer pathogenesis. We now show that high-density single nucleotide polymorphism (SNP) arrays can detect copy number alterations. By hybridizing genomic representations of breast and lung carcinoma cell line and lung tumor DNA to SNP arrays, and measuring locus-specific hybridization intensity, we detected both known and novel genomic amplifications and homozygous deletions in these cancer samples. Moreover, by combining genotyping with SNP quantitation, we could distinguish loss of heterozygosity events caused by hemizygous deletion from those that occur by copy-neutral events. The simultaneous measurement of DNA copy number changes and loss of heterozygosity events by SNP arrays should strengthen our ability to discover cancer-causing genes and to refine cancer diagnosis.

Alleles↗
PubMed2001

Cancer genomics: promises and complexities.

The impending final deciphering of the complete human genome, coupled with the advancement of high-throughput technologies, is positioned to bring about a fundamental transformation in cancer research. The era of molecular biology is transforming into the era of genomic biology, with an unprecedented promise of understanding multifactorial diseases and of identifying specific targets that can be used to develop patient-tailored therapies. Although the genomic approach is in an early phase of its development and its tools need to be honed, the application of genomic technologies to cancer research has already generated exciting results both in target identification and in disease classification. In this article, we review some of the developments pertinent to cancer research, discuss potentially problematic areas associated with them, and comment on future trends and issues.

DNA, Neoplasm↗
PubMed2001

Global and gene-specific epigenetic patterns in human bladder cancer genomes are relatively stable in vivo and in vitro over time.

We used a methylation-sensitive arbitrarily primed PCR technique to analyze, in a nonselective manner, methylation alterations at GC-rich regions of the genome in metachronous tumors and their derived cell lines from two patients with transitional cell carcinoma of the bladder. The methylation status of the majority of evaluable sequences (83%) remained unchanged in the tumors from both patients relative to a panel of normal urothelium samples obtained from individuals free of bladder disease, in which we measured <1% interindividual variation. The 17% of methylation alterations represents sequences altered in either a cancer-specific (3%), tumor-specific (1%), or patient-specific (13%) manner. The proportion of the altered sequences analyzed that were CpG islands corresponds to approximately 7000 CpG islands altered in the genome. Surprisingly, few additional changes in methylation patterns were observed in cell lines derived from the tumors; however, all of the cell lines showed altered methylation in a common set of 3% of evaluable sequences. Three genes known to be aberrantly methylated in bladder cancer (p16, p15, and PAX6) were studied in detail by methylation-sensitive single nucleotide primer extension and showed increased methylation in culture at preexisting methylated sites for all of the exons but no de novo methylation in culture for the promoters in any cell line. Therefore, our investigation provides the first serial as well as parallel quantitation of the global epigenetic stability in two independent bladder cancer genomes over the course of progression and in culture. In addition, our investigation also provides the first direct comparison of the epigenetic and genetic patterns on the global scale, showing the epigenetic pattern to be relatively stable in vivo and in vitro over time within an individual.

Carcinoma, Transitional Cell↗
PubMed2026

Amplification-Driven S100A11 Overexpression in Hepatocellular Carcinoma Is Associated with Metabolic Reprogramming, ECM Remodelling, and Immune Evasion: A Pan-Cancer Genomic Study.

BACKGROUND: S100A11, a calcium-binding S100 family protein, is increasingly implicated in carcinogenesis, yet its molecular regulation and clinical relevance across cancers remain unclear. Hepatocellular carcinoma (HCC) carries a dismal prognosis, in part due to a lack of reliable biomarkers for risk stratification of established disease. METHODS: We conducted a pan-cancer analysis of S100A11 genomic alterations across 31 studies (10,767 samples) obtained from TCGA, encompassing copy number alterations, somatic mutations, and DNA methylation. HCC-specific analyses evaluated S100A11 expression, its potential as a diagnostic/prognostic marker, co-expression networks, and pathway enrichment using TCGA-LIHC data, with univariate and multivariate Cox regression to assess survival associations. RESULTS: S100A11 alterations were predominantly driven by copy number amplification, with the highest frequencies in hepatobiliary cancers, lung and breast cancers. Copy number amplification showed a consistent inverse relationship with promoter methylation, indicating amplification-driven transcriptional activation. In HCC, S100A11 was markedly overexpressed compared with normal liver tissue, with strong diagnostic discriminatory capacity. High S100A11 expression was significantly associated with inferior overall survival (log-rank p = 0.032; HR = 1.46, 95% CI 1.03-2.06) and remained an independent predictor of overall survival after adjustment for age, sex, and AJCC pathologic stage (HR = 1.27, 95% CI 1.01-1.60, p = 0.038). Co-expression and pathway analyses demonstrated an association between S100A11 and metabolic reprogramming, extracellular matrix remodelling, and immune dysregulation. CONCLUSIONS: These findings identify S100A11 as a candidate diagnostic and prognostic biomarker in HCC whose overexpression is associated with metabolic reprogramming, ECM remodelling, and immune dysregulation, warranting experimental validation of a mechanistic role.

ECM↗
PubMed2002

Telomere dysfunction provokes regional amplification and deletion in cancer genomes.

Telomere dysfunction and associated fusion-breakage in the mouse encourages epithelial carcinogenesis and a more humanized genomic profile that includes nonreciprocal translocations (NRTs). Here, array comparative genomic hybridization was used to determine the pathogenic significance of NRTs and to determine whether telomere dysfunction also drives amplifications and deletions of cancer-relevant loci. Compared to tumors arising in mice with intact telomeres, tumors with telomere dysfunction possessed higher levels of genomic instability and showed numerous amplifications and deletions in regions syntenic to human cancer hotspots. These observations suggest that telomere-based crisis provides a mechanism of chromosomal instability, including regional amplifications and deletions, that drives carcinogenesis. This model provides a platform for discovery of genes responsible for the major cancers affecting aged humans.

Animals↗
PubMed1997

Ovarian cancer genomic instability correlates with p53 frameshift mutations.

We hypothesize that genomic instability plays an important role in causing specific types of p53 mutations in ovarian cancer. To test this hypothesis, 78 tumors were analyzed for p53 mutations with SSCP analysis of the entire open reading frame. At the same time, alterations in 10 microsatellite loci including di-, tri-, and tetranucleotide repeats were evaluated. Fourteen (26%) of all mutations were insertion/deletion mutations. All insertion/deletion mutations were associated with one of the following features: runs of purines or pyrimidines, repeats of short sequences, or palindromes. There was a strong association of generalized microsatellite instability with p53 in contrast to tumors with other types of mutations or wild-type p53 (P = 0.007). These characteristic p53 mutations appear to be caused by generalized genomic instability rather than to be the direct cause of genomic instability. These findings suggest the existence of additional novel DNA repair genes important to the carcinogenic process.

Carcinoma↗
PubMed1998

Breast cancer genome anatomy: correlation of morphological changes in breast carcinomas with expression of the novel gene product Di12.

To determine which genes may be activated or inactivated during breast cancer development, we employed two cloning strategies (subtractive hybridization and differential display) using RNA samples from a human breast tumor and its matching normal breast cell line. Of 950 clones isolated, 102 cDNA inserts were analysed by DNA sequencing and database searching. We found 30 clones that were obviously unidentified, with no significant homology to any listed human gene. We focused upon one of the novel genes, Di12, that is differentially expressed as a 1.35 kb RNA in breast cancer tissues and cell-lines, and in several normal tissues. A full length cDNA of this gene was cloned, and its DNA sequence revealed an open reading frame of 339 amino acids. Antibodies to the ten N-terminal amino acids were developed to investigate the expression of Di12 in breast cancer cell-lines and tumors. The Di12 protein was found in tissue sections of infiltrating ductal carcinomas (IDCs), but not in benign or normal breast specimens. RT-PCR analysis confirmed expression of Di12 in 80% of infiltrating ductal carcinomas (IDCs). As IDC constitutes approximately 70% of breast cancers seen clinically, the level of Di12 expression may be predictive of disease progression.

Amino Acid Sequence↗
PubMed2002

Integrating cancer genomics and proteomics in the post-genome era.

The dawn of the post-genome era is leading to extraordinary opportunities in biomedicine. Our group has embarked on a major effort to integrate genomics, transcriptomics and proteomics for the profiling of tumor tissues, an approach we refer to as operomics. Our major goals are the molecular classification of tumors and the identification of markers for the early detection of cancer. Molecular analyses of tumors rely on microdissected tissues, which are simultaneously investigated for genomic, transcriptomic and proteomic changes. Genomic alterations in tumor cells being investigated include deletions, amplifications and methylation changes across the entire genome as well as point mutations in specific genes. Expression analysis at the RNA level is being undertaken using oligonucleotide and cDNA based microarrays. An important aspect of our approach is the large-scale identification and quantitative analysis of tumor proteins in whole cell lysates as well as in protein compartments. Protein separation strategies include two-dimensional polyacrylamide gel electrophoresis and liquid chromatography. Specific protein subsets, of interest include membrane proteins, secreted proteins and antigenic proteins as sources of biomarkers for early detection of cancer. Our current approach is illustrated with findings stemming from our studies of human gliomas.

Brain Neoplasms↗
PubMed2026

Protein arginine methyltransferase (PRMT8) in cancer: Genomic alterations, subcellular dynamics, and clinical implications.

PRMT8 encodes a protein arginine methyltransferase, which is primarily expressed in the brain and nervous system. Several studies have reported its alterations, which have been implicated in various cancers. However, the existing information remains unsystematic and fragmented due to inconsistency in methodology. This review aims to explore PRMT8 gene alterations in humans, their effects on cellular function and physiology, and their clinical implications. We conducted a narrative literature review covering all publications on PRMT8 alterations across different cancer types, their effect on tumour cell characteristics, and their impact on patient prognosis. Reported PRMT8 alterations include mutations, copy number amplifications, and single-nucleotide polymorphisms, which lead to overexpression or downregulation of PRMT8 protein in tumour cells. PRMT8 alterations compromise the efficacy of both chemotherapy and immune checkpoint inhibitor treatment. These alterations enable tumour cells to maintain pluripotency via activation of the PI3K/AKT/SOX2 signalling pathway, thereby promoting cellular proliferation, invasion, and colony formation. Clinically, these PRMT8 alterations drive disease progression and therapy resistance, resulting in poor prognosis and reduced patient survival. These findings underscore the need to incorporate PRMT8 alterations assessment in clinical practice to guide therapeutic decision-making and improve treatment outcomes in affected patient populations.

Humans↗