Personalized Onco-genomics
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Personalized Onco-genomics
Personalized onco-genomics (POG) is the field of oncology and genomics that is focused on using whole genome analysis to make personalized clinical treatment decisions. The program was devised at British Columbia's BC Cancer Agency and is currently being led by Marco Marra and Janessa Laskin. Genome instability has been identified as one of the underlying hallmarks of cancer. The genetic diversity of cancer cells promotes multiple other cancer hallmark functions that help them survive in their microenvironment and eventually metastasise. The pronounced genomic heterogeneity of tumours has led researchers to develop an approach that assesses each individual's cancer to identify targeted therapies that can halt cancer growth. Identification of these "drivers" and corresponding medications used to possibly halt these pathways are important in cancer treatment. With the oncogenomic databases that currently recognize mutation and abnormalities in the genomic structure of cancer cells, ...
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Oncology
Oncology is a branch of medicine that deals with the study, treatment, diagnosis and prevention of cancer. A medical professional who practices oncology is an ''oncologist''. The name's etymological origin is the Greek word ὄγκος (''ónkos''), meaning "tumor", "volume" or "mass". Oncology is concerned with: * The diagnosis of any cancer in a person (pathology) * Therapy (e.g. surgery, chemotherapy, radiotherapy and other modalities) * Follow-up of cancer patients after successful treatment * Palliative care of patients with terminal malignancies * Ethical questions surrounding cancer care * Screening efforts: ** of populations, or ** of the relatives of patients (in types of cancer that are thought to have a hereditary basis, such as breast cancer) Diagnosis Medical histories remain an important screening tool: the character of the complaints and nonspecific symptoms (such as fatigue, weight loss, unexplained anemia, fever of unknown origin, paraneoplastic phenome ...
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Non-small-cell Lung Carcinoma
Non-small-cell lung cancer (NSCLC) is any type of epithelial lung cancer other than small-cell lung carcinoma (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitive to chemotherapy, compared to small-cell carcinoma. When possible, they are primarily treated by surgical resection with curative intent, although chemotherapy has been used increasingly both preoperatively (Neoadjuvant therapy, neoadjuvant chemotherapy) and postoperatively (Adjuvant therapy, adjuvant chemotherapy). Types The most common types of NSCLC are squamous-cell carcinoma, large-cell carcinoma, and adenocarcinoma, but several other types occur less frequently. A few of the less common types are pleomorphic, carcinoid tumor, salivary gland carcinoma, and unclassified carcinoma. All types can occur in unusual histologic variants and as mixed cell-type combinations. Nonsquamous-cell carcinoma almost occupies the half of NSCLC. In the tissue classification, the cent ...
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Indel
Indel is a molecular biology term for an insertion or deletion of bases in the genome of an organism. It is classified among small genetic variations, measuring from 1 to 10 000 base pairs in length, including insertion and deletion events that may be separated by many years, and may not be related to each other in any way. A microindel is defined as an indel that results in a net change of 1 to 50 nucleotides. In coding regions of the genome, unless the length of an indel is a multiple of 3, it will produce a frameshift mutation. For example, a common microindel which results in a frameshift causes Bloom syndrome in the Jewish or Japanese population. Indels can be contrasted with a point mutation. An indel inserts or deletes nucleotides from a sequence, while a point mutation is a form of substitution that ''replaces'' one of the nucleotides without changing the overall number in the DNA. Indels can also be contrasted with Tandem Base Mutations (TBM), which may result from fun ...
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Mitochondrial DNA
Mitochondrial DNA (mtDNA or mDNA) is the DNA located in mitochondria, cellular organelles within eukaryotic cells that convert chemical energy from food into a form that cells can use, such as adenosine triphosphate (ATP). Mitochondrial DNA is only a small portion of the DNA in a eukaryotic cell; most of the DNA can be found in the cell nucleus and, in plants and algae, also in plastids such as chloroplasts. Human mitochondrial DNA was the first significant part of the human genome to be sequenced. This sequencing revealed that the human mtDNA includes 16,569 base pairs and encodes 13 proteins. Since animal mtDNA evolves faster than nuclear genetic markers, it represents a mainstay of phylogenetics and evolutionary biology. It also permits an examination of the relatedness of populations, and so has become important in anthropology and biogeography. Origin Nuclear and mitochondrial DNA are thought to be of separate evolutionary origin, with the mtDNA being derived ...
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Regulatory Elements
A regulatory sequence is a segment of a nucleic acid molecule which is capable of increasing or decreasing the expression of specific genes within an organism. Regulation of gene expression is an essential feature of all living organisms and viruses. Description In DNA, regulation of gene expression normally happens at the level of RNA biosynthesis (transcription). It is accomplished through the sequence-specific binding of proteins (transcription factors) that activate or inhibit transcription. Transcription factors may act as activators, repressors, or both. Repressors often act by preventing RNA polymerase from forming a productive complex with the transcriptional initiation region ( promoter), while activators facilitate formation of a productive complex. Furthermore, DNA motifs have been shown to be predictive of epigenomic modifications, suggesting that transcription factors play a role in regulating the epigenome. In RNA, regulation may occur at the level of protein ...
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Promoter (genetics)
In genetics, a promoter is a sequence of DNA to which proteins bind to initiate transcription of a single RNA transcript from the DNA downstream of the promoter. The RNA transcript may encode a protein (mRNA), or can have a function in and of itself, such as tRNA or rRNA. Promoters are located near the transcription start sites of genes, upstream on the DNA (towards the 5' region of the sense strand). Promoters can be about 100–1000 base pairs long, the sequence of which is highly dependent on the gene and product of transcription, type or class of RNA polymerase recruited to the site, and species of organism. Promoters control gene expression in bacteria and eukaryotes. RNA polymerase must attach to DNA near a gene for transcription to occur. Promoter DNA sequences provide an enzyme binding site. The -10 sequence is TATAAT. -35 sequences are conserved on average, but not in most promoters. Artificial promoters with conserved -10 and -35 elements transcribe more slowly. All D ...
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Introns
An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e. a region inside a gene."The notion of the cistron .e., gene... must be replaced by that of a transcription unit containing regions which will be lost from the mature messenger – which I suggest we call introns (for intragenic regions) – alternating with regions which will be expressed – exons." (Gilbert 1978) The term ''intron'' refers to both the DNA sequence within a gene and the corresponding RNA sequence in RNA transcripts. The non-intron sequences that become joined by this RNA processing to form the mature RNA are called exons. Introns are found in the genes of most organisms and many viruses and they can be located in both protein-coding genes and genes that function as RNA (noncoding genes). There are four main types of introns: tRNA introns, group I introns, group II introns, and s ...
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Untranslated Region
In molecular genetics, an untranslated region (or UTR) refers to either of two sections, one on each side of a coding sequence on a strand of mRNA. If it is found on the 5' side, it is called the 5' UTR (or leader sequence), or if it is found on the 3' side, it is called the 3' UTR (or trailer sequence). mRNA is RNA that carries information from DNA to the ribosome, the site of protein synthesis (translation) within a cell. The mRNA is initially transcribed from the corresponding DNA sequence and then translated into protein. However, several regions of the mRNA are usually not translated into protein, including the 5' and 3' UTRs. Although they are called untranslated regions, and do not form the protein-coding region of the gene, uORFs located within the 5' UTR can be translated into peptides. The 5' UTR is upstream from the coding sequence. Within the 5' UTR is a sequence that is recognized by the ribosome which allows the ribosome to bind and initiate translation. Th ...
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Non-coding DNA
Non-coding DNA (ncDNA) sequences are components of an organism's DNA that do not encode protein sequences. Some non-coding DNA is transcribed into functional non-coding RNA molecules (e.g. transfer RNA, microRNA, piRNA, ribosomal RNA, and regulatory RNAs). Other functional regions of the non-coding DNA fraction include regulatory sequences that control gene expression; scaffold attachment regions; origins of DNA replication; centromeres; and telomeres. Some non-coding regions appear to be mostly nonfunctional such as introns, pseudogenes, intergenic DNA, and fragments of transposons and viruses. Fraction of non-coding genomic DNA In bacteria, the coding regions typically take up 88 % of the genome. The remaining 12 % consists largely of non-coding genes and regulatory sequences, which means that almost all of the bacterial genome has a function. The amount of coding DNA in eukaryrotes is usually a much smaller fraction of the genome because eukaryotic genomes contai ...
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Coding Region
The coding region of a gene, also known as the coding sequence (CDS), is the portion of a gene's DNA or RNA that codes for protein. Studying the length, composition, regulation, splicing, structures, and functions of coding regions compared to non-coding regions over different species and time periods can provide a significant amount of important information regarding gene organization and evolution of prokaryotes and eukaryotes. This can further assist in mapping the human genome and developing gene therapy. Definition Although this term is also sometimes used interchangeably with exon, it is not the exact same thing: the exon is composed of the coding region as well as the 3' and 5' untranslated regions of the RNA, and so therefore, an exon would be partially made up of coding regions. The 3' and 5' untranslated regions of the RNA, which do not code for protein, are termed non-coding regions and are not discussed on this page. There is often confusion between coding region ...
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Exome
The exome is composed of all of the exons within the genome, the sequences which, when transcribed, remain within the mature RNA after introns are removed by RNA splicing. This includes untranslated regions of messenger RNA (mRNA), and coding regions. Exome sequencing has proven to be an efficient method of determining the genetic basis of more than two dozen Mendelian or single gene disorders. Statistics The human exome consists of roughly 233,785 exons, about 80% of which are less than 200 base pairs in length, constituting a total of about 1.1% of the total genome, or about 30 megabases of DNA. Though composing a very small fraction of the genome, mutations in the exome are thought to harbor 85% of mutations that have a large effect on disease. Definition It is important to note that the exome is distinct from the transcriptome, which is all of the transcribed RNA within a cell type. While the exome is constant from cell-type to cell-type, the transcriptome changes ...
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Copy-number Variation
Copy number variation (CNV) is a phenomenon in which sections of the genome are repeated and the number of repeats in the genome varies between individuals. Copy number variation is a type of structural variation: specifically, it is a type of Gene duplication, duplication or deletion (genetics), deletion event that affects a considerable number of base pairs. Approximately two-thirds of the entire human genome may be composed of repeats and 4.8–9.5% of the human genome can be classified as copy number variations. In mammals, copy number variations play an important role in generating necessary variation in the population as well as disease phenotype. Copy number variations can be generally categorized into two main groups: short repeats and long repeats. However, there are no clear boundaries between the two groups and the classification depends on the nature of the locus (genetics), loci of interest. Short repeats include mainly Tandem repeat, dinucleotide repeats (two repeat ...
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