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63-412: TCGA may refer to: The Cancer Genome Atlas The Center for Genetic Anthropology at University College London Taxation of Chargeable Gains Act 1992 Thomas Cook Group Airlines Limited - entered compulsory liquidation 23 September 2019 Topics referred to by the same term [REDACTED] This disambiguation page lists articles associated with

126-462: A blood vessel is blocked by a blood clot or when a blood vessel ruptures, causing blood to leak to the brain. If the brain cannot get enough oxygen and blood, brain cells can die, leading to permanent damage. The spinal cord transmits sensory reception from the peripheral nervous system . It also conducts motor information to the body's skeletal muscles , cardiac muscles , smooth muscles , and glands . There are 31 pairs of spinal nerves along

189-601: A TCGA Program Office to help manage the project. Dr. Jean Claude Zenklusen has been the director of the office since August 2013. The TCGA Program Office was responsible for the operation of six Genome Characterization Centers, seven Genome Analysis Centers, the Biospecimen Core Resource, the Data Coordination Center, and approximately one third of the sequencing done for the project by the three Genome Sequencing Centers. In addition,

252-406: A bacterial or viral infection. Fever, vomiting, and a stiff neck are all symptoms of meningitis. A chronic, often debilitating neurological disorder characterized by recurrent moderate to severe headaches, often in association with a number of autonomic nervous system symptoms. Multiple sclerosis (MS) is a chronic, inflammatory demyelinating disease , meaning that the myelin sheath of neurons

315-636: A distinct subset of glioma samples which displays concerted hypermethylation at a large number of loci, indicating the existence of a glioma- CpG island methylator phenotype ( G-CIMP ). G-CIMP tumors belong to the proneural subgroup and were tightly associated with IDH1 somatic mutations. TCGA reported on mRNA expression, microRNA expression, promoter methylation, DNA copy number, and exome sequencing of 316 tumor samples of high grade serous ovarian cancer in Nature in June 2011. The researchers found mutations of

378-611: A material transfer agreement with TCGA. In 2009, NCI removed approximately $ 130 million of ARRA from the NCI's "Prime Contract" with Science Applications International Corporation (SAIC) to fund tissue accrual and a variety of other activities through the NCI Office of Acquisition. $ 42 million was available for tissue accrual through NCI using "Requests for Quotations" (RFQs) and "Requests for Proposals" (RFPs) to generate purchase orders and contracts, respectively. RFQs were primarily used for

441-514: A starting point for collecting samples from any type of tumor, including a minimum of 200  mg in size, no less than 80% tumor nuclei and a matched source of germline DNA (such as blood or purified DNA ). In addition, institutions submitting tissues to TCGA were required to include a minimal clinical data set as defined by the Disease Working Group, signed consents which have been approved by their institution's IRB, as well as

504-462: A team of scientists from various institutions and assessment of multiple burgeoning high-throughput technologies. TCGA wanted to not only generate high-quality and biologically meaningful genomic data, but also make that data freely available to the cancer research community. Three tumor types were explored during the pilot phase, glioblastoma multiforme (GBM) and high-grade serous ovarian adenocarcinoma, and lung squamous carcinoma. Following success of

567-457: A tens of thousands of potential DNA regulatory elements specific to different cancers and cell types. This provided insights into how gene dysregulation could help drive cancer initiation and progression. Understanding chromatin accessibility of known immune cell-specific regulatory elements also provided clues into the immune microenvironment and the availability of immunotherapy targets. The study, “The chromatin landscape of primary human cancers,”

630-438: A whole. The main topics are (1) cell-of-origin patterns, which groups and analyzes tumors based on biological system or histological subtype; (2) oncogenic processes, which considers the complex downstream impacts alterations may have on molecular pathways and the microenvironment, and (3) signaling pathways, which surveys the role different pathways play in different cancers and their potential vulnerabilities. The completion of

693-448: Is a condition where in the immune system attacks and destroys healthy body tissue. This is caused by a loss of tolerance to proteins in the body, resulting in immune cells recognising these as 'foreign' and directing an immune response against them. A stroke is an interruption of the blood supply to the brain. Approximately every 40 seconds, someone in the US has a stroke. This can happen when

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756-404: Is a group of nerves housed inside the spine that runs almost its entire length. Tourette's syndrome is an inherited neurological disorder. Early onset may be during childhood, and it is characterized by physical and verbal tics . Tourette's often also includes symptoms of both OCD and ADHD indicating a link between the three disorders. The exact cause of Tourette's, other than genetic factors,

819-456: Is an increased risk of the development of Dementia with Lewy bodies , or (DLB), and a direct genetic association of Attention deficit disorder to Parkinson's disease two progressive, and serious, neurological diseases whose symptoms often occur in people over age 65. Autism is a neurodevelopmental disorder that is characterized by repetitive patterns of behavior and persistent deficits in social interaction and communication. Tumors of

882-488: Is an inflammation of the brain. It is usually caused by a foreign substance or a viral infection . Symptoms of this disease include headache, neck pain, drowsiness, nausea, and fever. If caused by the West Nile virus , it may be lethal to humans, as well as birds and horses. Epilepsy is an unpredictable, serious, and potentially fatal disorder of the nervous system, thought to be the result of faulty electrical activity in

945-439: Is an organic disorder of the nervous system. ADHD, which in severe cases can be debilitating, has symptoms thought to be caused by structural as well as biochemical imbalances in the brain; in particular, low levels of the neurotransmitters dopamine and norepinephrine, which are responsible for controlling and maintaining attention and movement. Many people with ADHD continue to have symptoms well into adulthood. Also of note

1008-467: Is damaged , significant impairments in cognition and physiological function or death may occur. Addiction is a disorder of the brain's reward system which arises through transcriptional and epigenetic mechanisms and occurs over time from chronically high levels of exposure to an addictive stimulus (e.g., morphine, cocaine, sexual intercourse, gambling, etc.). Arachnoid cysts are cerebrospinal fluid covered by arachnoidal cells that may develop on

1071-444: Is damaged. Symptoms of MS include visual and sensation problems, muscle weakness, numbness and tingling all over, muscle spasms, poor coordination, and depression . Also, patients with MS have reported extreme fatigue and dizziness, tremors, and bladder leakage. Myelopathy is an injury to the spinal cord due to severe compression that may result from trauma, congenital stenosis, degenerative disease or disc herniation. The spinal cord

1134-448: Is unknown. Alzheimer's is a neurodegenerative disease typically found in people over the age of 65 years. Worldwide, approximately 24 million people have dementia ; 60% of these cases are due to Alzheimer's. The ultimate cause is unknown. The clinical sign of Alzheimer's is progressive cognition deterioration. Huntington's disease is a degenerative neurological disorder that is inherited. Degeneration of neuronal cells occurs throughout

1197-717: The Broad Institute, Harvard, University of North Carolina, MD Anderson Cancer Center, Van Andel Institute, Baylor College of Medicine and the British Columbia Cancer Center. The Data Coordinating Center (DCC) was the central repository for TCGA data. It was also responsible for the quality control of data entering the TCGA database. The DCC also maintained the TCGA Data Portal, which was where users could access processed TCGA data. This work

1260-593: The Genomic Data Commons). Most of the processed TCGA data is completely open access. For data that could potentially identify specific patients, users apply for controlled-data access to the Data Access Committee (DAC), which evaluates whether the end user is a bona fide researcher and is asking a legitimate scientific question that merits access to individual-level data. Data access credentials are now managed through NIH's dbGAP . Since

1323-568: The Mouse Organogenesis Cell Atlas (MOCA) were elaborated by machine learning and deep learning to compare and find correlation between cancer and embryonic cells in early cell development and differentiation . They were also applied to distinguish changes in gene expression patterns between various types of tumors from an unknown source. Number Analyzed in Original Marker Paper In 2008,

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1386-599: The NCI/NHGRI were responsible for the integration of data across all characterization and sequencing centers as well as biological interpretation of TCGA data. The GDACs included The Broad Institute, University of North Carolina, Oregon Health and Science University, University of California, Santa Cruz, MD Anderson Cancer Center, Memorial Sloan Kettering Cancer Center, and The Institute for Systems Biology. All seven GDACs worked together to develop an integrated data analysis pipeline. A preliminary list of tumors for TCGA to study

1449-642: The Pan-Cancer Atlas marked the official end of TCGA as a program, though the data, analysis methods, and other resources produced by TCGA continues to serve as a resource for researchers. For example, TCGA’s whole-genome data were analyzed as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG), an international effort to analyze 2,600 cancer whole genomes to understand somatic and germline variations in both coding and non-coding regions. TCGA researchers also set out to systematically study

1512-692: The TCGA Project Office was responsible for coordinating the accrual of tissues for TCGA. Dr. Carolyn Hutter, project manager for NHGRI, directed two thirds of the sequencing at the Genome Sequencing Centers. Members from the NCI and the NHGRI teams, along with principal investigators funded by the project, comprised the Steering Committee. The Steering Committee was tasked with overseeing the scientific validity of

1575-407: The TCGA published its first results on glioblastoma multiforme (GBM) in Nature . These first results characterized and analyzed 91 tumor-normal matched pairs. While 587 biospecimens were collected for the study, most were rejected during quality control: the tumor samples needed to contain at least 80% tumor nuclei and no more than 50% necrosis, and a secondary pathology assessment had to agree that

1638-408: The brain or spinal cord. A medical condition, Locked-in syndrome usually resulting from a stroke that damages part of the brainstem, in which the body and most of the facial muscles are paralysed but consciousness remains and the ability to perform certain eye movements is preserved. Meningitis is an inflammation of the meninges (membranes) of the brain and spinal cord. It is most often caused by

1701-487: The brain or spinal cord. They are a congenital disorder , and in some cases may not show symptoms. However, if there is a large cyst, symptoms may include headache, seizures, ataxia (lack of muscle control), hemiparesis , and several others. Macrocephaly and ADHD are common among children, while presenile dementia, hydrocephalus (an abnormality of the dynamics of the cerebrospinal fluid), and urinary incontinence are symptoms for elderly patients (65 and older). ADHD

1764-518: The brain, especially in the striatum . There is a progressive decline that results in abnormal movements. Statistics show that Huntington's disease may affect 10 per 100,000 people of Western European descent. Parkinson's disease, or PD, is a progressive illness of the nervous system. Caused by the death of dopamine-producing brain cells that affect motor skills and speech. Symptoms may include bradykinesia (slow physical movement), muscle rigidity, and tremors. Behavior, thinking, sensation disorders, and

1827-578: The brain. Epileptic seizures result from abnormal, excessive, or hypersynchronous neuronal activity in the brain. About 50 million people worldwide have epilepsy, and nearly 80% of epilepsy occurs in developing countries. Epilepsy becomes more common as people age. Onset of new cases occurs most frequently in infants and the elderly. Epileptic seizures may occur in recovering patients as a consequence of brain surgery. A number of different pathogens (i.e., certain viruses , bacteria , protozoa , fungi , and prions ) can cause infections that adversely affect

1890-607: The central nervous system constitute around 2% of all cancer in the United States. Catalepsy is a nervous disorder characterized by immobility and muscular rigidity, along with a decreased sensitivity to pain. Catalepsy is considered a symptom of serious diseases of the nervous system (e.g., Parkinson's disease , Epilepsy , etc.) rather than a disease by itself. Cataleptic fits can range in duration from several minutes to weeks. Catalepsy often responds to Benzodiazepines (e.g., Lorazepam ) in pill and I.V. form. Encephalitis

1953-479: The characteristics of the typical tissue samples accrued as "standard of care" in the United States and how TCGA could best utilize the tissue. For example, the Brain Disease Working Group determined that samples containing more than 50% necrosis would not be suitable for TCGA and that 80% tumor nuclei were required in the viable portion of the tumor. TCGA followed some general guidelines as

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2016-633: The characterization and basic analyses covering 33 cancer types. For several cancer types, such as bladder urothelial carcinoma and GBM, additional cases were collected and a second analysis was performed. In 2013, TCGA published an initial Pan-Cancer analysis describing the "mutational landscape" defined as frequently recurring mutations identified from exome sequencing of 3,281 tumours from 12 commonly occurring cancer subtypes. The twelve subtypes studied were breast adenocarcinoma , lung adenocarcinoma , lung squamous cell carcinoma , endometrial carcinoma , glioblastoma multiforme , squamous cell carcinoma of

2079-694: The clinical data for their samples and to enter into collaborations with other institutions that had similar data on TCGA samples, thus increasing the power of outcome analysis. TCGA managed a number of different types of centers that were funded to generate and analyze data. TCGA was the first large-scale genomics project funded by the NIH to include significant resources to bioinformatic discovery. The NCI has devoted 50% of TCGA appropriated funds, approximately $ 12M/year, to fund bioinformatic discovery. Genome Characterization Centers and Genome Sequencing Centers generated data. Two separate Genome Data Analysis Centers utilized

2142-549: The collection of retrospective samples from established banks while RFPs were used for the prospective collection of samples. TCGA finalized sample collection in December, 2013, with nearly 20,000 biospecimens. Institutions that contributed samples to TCGA were paid, and gained advance access to molecular data generated on their samples, while maintaining a link between the TCGA unique identifier and their own unique identifier. This permitted contributing institutions to link back to

2205-414: The data for bioinformatic discovery. Two centers were funded to isolate biomolecules from patient samples and one center is funded to store the data. This workflow has evolved over the years and is not known as NCI's Genome Characterization Pipeline. The Biospecimen Core Resource (BCR) was responsible for verifying the quality and quantity of tissue shipped by tissue source sites, isolating DNA and RNA from

2268-516: The exome sequence, DNA copy number, promoter methylation and messenger RNA characterization of 276 tumor samples of colon and rectal cancers in Nature in July 2012. 97 of the samples also underwent ultra-low coverage whole genome sequencing. TCGA researchers discovered the same type of alterations in colon and rectal tumors, indicating that they are a single type of cancer. Some differences, such as hypermethylation, were apparent in tumors originating in

2331-412: The face, back, arms, or legs; an inability to concentrate; loss of feeling; memory loss; loss of muscle strength; tremors ; seizures; increased reflexes, spasticity, tics; paralysis; and slurred speech . One should seek medical attention if affected by these. Any type of traumatic brain injury (TBI) or injury done to the spinal cord can result in a wide spectrum of disabilities in a person. Depending on

2394-446: The formation of the cerebral cortex include microgyria , polymicrogyria , bilateral frontoparietal polymicrogyria , and pachygyria . A tumor is an abnormal growth of body tissue. In the beginning, tumors can be noncancerous, but if they become malignant, they are cancerous. In general, they appear when there is a problem with cellular division . Problems with the body's immune system can lead to tumors. An autoimmune disorder

2457-544: The gene TP53 in an overwhelming 96% of the cases analyzed, Recurrent mutations at lower frequency were found in a handful of other genes, including NF1 , BRCA1 , BRCA2 , RB1 and CDK12 . TCGA researchers were also able to identify gene expression patterns that correlated with patient survival. They defined four subtypes of the cancer according to gene expression and DNA methylation patterns: immunoreactive, differentiated, proliferative, and mesenchymal. They also identified 68 genes as potential drug targets. TCGA reported on

2520-609: The genomic characterization and sequence analysis of 20–25 different tumor types by 2014. Ultimately, TCGA surpassed that goal, characterizing 33 cancer types including 10 rare cancers. The project initially set out to collect and characterize 500 patient samples, more than most genomics studies of its time, and used a variety of different molecular techniques. Techniques included gene expression profiling , copy number variation profiling, SNP genotyping , genome wide DNA methylation profiling, microRNA profiling, and exon sequencing . With restraints of nascent technology and costs at

2583-555: The head and neck, colon cancer , rectal cancer , bladder cancer , kidney clear cell carcinoma , ovarian carcinoma and acute myeloid leukaemia . In 2018, the TCGA Research Network published what is collectively known as the Pan-Cancer Atlas: a collection of 35 papers summarizing the work accomplished by TCGA and describing overarching themes of cancer biology elucidated by analyzing all of TCGA data as

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2646-1351: The more common the cancer type, the more likely that samples would be accrued quickly for study. This resulted in common tumor types, such as colon, lung and breast cancer becoming the first tumor types entered into the project, before rare tumor types. Cancer types selected for study byTCGA included: lung squamous cell carcinoma , kidney papillary carcinoma , clear cell kidney carcinoma , breast ductal carcinoma , renal cell carcinoma , cervical cancer (squamous), colon adenocarcinoma , stomach adenocarcinoma , rectal carcinoma , hepatocellular carcinoma , Head and neck (oral) squamous cell carcinoma, thyroid carcinoma , bladder urothelial carcinoma – nonpapillary, uterine corpus ( endometrial carcinoma ), pancreatic ductal adenocarcinoma , acute myeloid leukemia , prostate adenocarcinoma , lung adenocarcinoma , cutaneous melanoma , breast lobular carcinoma and lower grade glioma , esophageal carcinoma , ovarian serous cystadenocarcinoma , lung squamous cell carcinoma , adrenocortical carcinoma , Diffuse Large B-cell lymphoma , paraganglioma & pheochromocytoma , cholangiocarcinoma , uterine carcinosarcoma , uveal melanoma , thymoma , sarcoma , mesothelioma , and testicular germ cell cancer. TCGA began accruing samples for all of these tumor types simultaneously. The tumor types with

2709-480: The most samples accrued were entered into the characterization pipeline first. The rarer tumor types which were more difficult to accrue and tumor types for which TCGA could not identify a source of high-quality samples were entered into the TCGA production pipeline in the second year of the project. This gave the TCGA Program Office additional time to accrue sufficient samples for the project. TCGA and

2772-441: The non-coding regions of the genome of multiple cancers. The team applied the assay for transposase-accessible chromatin using sequencing (ATAC-seq) to 410 TCGA tumor samples covering 23 primary cancers in order to gain insights into gene dysregulation in cancer. ATAC-seq is a low-cost method for identifying regions of open or active chromatin and positions of DNA-binding proteins. Through ATAC-seq, researchers were able to identify

2835-474: The original diagnosis of GBM was accurate. A last batch of samples was excluded because the DNA or RNA collected was not of sufficient quality or quantity to be analyzed by all of the different platforms used in the study. All of the data from this study, as well as data that has been collected since the publication were made publicly available at TCGA's Data Coordinating Center (DCC) for public access (later moved toe

2898-638: The pilot phase, TCGA expanded its effort to characterize additional cancer types and provide a rich and large genomic data set for further cancer research discovery. TCGA was co-managed by scientists and managers from the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI). With the expansion of TCGA from the pilot phase to Phase II in October 2009, NCI created

2961-404: The project while the NCI/NHGRI administrative team ensured that the scientific progress and goals of the project were met, the project was completed on time and on budget, and the various components of the project worked together. Tissue requirements varied from tissue type to tissue type and from cancer type to cancer type. Disease experts from the project's Disease Working Groups helped to define

3024-506: The publication of the first marker paper, several analysis groups within the TCGA Network have presented more detailed analyses of the glioblastoma data. An analysis group led by Roel Verhaak, PhD, Katherine A. Hoadley , PhD, and D. Neil Hayes , MD, successfully correlated glioma gene expression subtypes with genomic abnormalities. The DNA methylation data analysis team, led by Houtan Noushmehr, PhD and Peter Laird, PhD, identified

3087-602: The right colon. A subset of the tumors were found to be hypermutated; a majority of those also had high microsatellite instability. Two dozen significantly mutated genes and recurring copy number alterations were found. The study suggested new markers for aggressive colorectal carcinoma and an important role for MYC-directed transcriptional activation and repression. Fueled by the American Recovery and Reinvestment Act of 2009, NIH extended TCGA to cover 20 types of cancer. This included an effort to study rare cancers, which

3150-623: The samples, performing quality control of these biomolecules, and shipping processed samples to the GSCs and GCCs. The International Genomics Consortium was awarded the contract to initiate the BCR for the pilot project. There were two BCRs funded by NCI at the start of the full project: Nationwide Children's Hospital and the International Genomics Consortium. The BCRs were recompeted in 2010 and Nationwide Children's Hospital

3213-410: The section of the brain or spinal cord that experiences the trauma, the outcome may be anticipated. Infectious diseases are transmitted in several ways. Some of these infections may affect the brain or spinal cord directly. Generally, an infection is a disease that is caused by the invasion of a microorganism or virus. Degenerative spinal disorders involve a loss of function in the spine. Pressure on

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3276-581: The sometimes co-morbid skin condition Seborrheic dermatitis are just some of PD's numerous nonmotor symptoms. Parkinson's disease , Attention deficit/hyperactivity disorder (ADHD) and Bi-polar disorder , all appear to have some connection to one another, as all three nervous system disorders involve lower than normal levels of the brain chemical dopamine (In ADHD, Parkinson's, and the depressive phase of Bi-polar disorder.) or too much dopamine (in Mania or Manic states of Bi-polar disorder ) in different areas of

3339-570: The spinal cord and nerves may be associated with herniation or disc displacement. Brain degeneration also causes central nervous system diseases (i.e. Alzheimer's , Lewy body dementia , Parkinson's , and Huntington's diseases ). Studies have shown that obese people may have severe degeneration in the brain due to loss of tissue affecting cognition . Common structural defects include birth defects, anencephaly , and spina bifida . Children born with structural defects may have malformed limbs, heart problems, and facial abnormalities. Defects in

3402-407: The spinal cord, all of which consist of both sensory and motor neurons . The spinal cord is protected by vertebrae and connects the peripheral nervous system to the brain, and it acts as a "minor" coordinating center. The brain serves as the organic basis of cognition and exerts centralized control over the other organs of the body. The brain is protected by the skull ; however, if the brain

3465-482: The start of the project, many array-based technologies and limited targeted gene sequencing were performed. During II, TCGA was able to begin performing whole exome and whole transcriptome sequencing on all cases and whole genome sequencing on 10% of the cases used in the project. The goal of TCGA's pilot project was to establish an infrastructure to collect, molecularly characterize, and analyze 500 cancers and matched controls. The work required extensive cooperation among

3528-454: The title TCGA . If an internal link led you here, you may wish to change the link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=TCGA&oldid=929736212 " Category : Disambiguation pages Hidden categories: Short description is different from Wikidata All article disambiguation pages All disambiguation pages The Cancer Genome Atlas TCGA

3591-418: The treatments. Central nervous system tumors are the most common forms of pediatric cancer. Brain tumors are the most frequent and have the highest mortality. Some disorders, such as substance addiction , autism , and ADHD may be regarded as CNS disorders, though the classifications are not without dispute. Every disease has different signs and symptoms . Some of them are persistent headache; pain in

3654-517: Was awarded the contract. Three Genome Sequencing Centers (GCCs) were co-funded by NCI and NHGRI: the Broad Institute , McDonnell Genome Institute at Washington University and Baylor College of Medicine . All three of these sequencing centers have shifted from Sanger sequencing to next-generation sequencing (NGS). A variety of NGS technologies were tested and implemented simultaneously. The NCI funded seven Genome characterization centers:

3717-445: Was enabled with support from patients, patient advocacy groups, and doctors. Starting in 2011, TCGA began holding Annual Scientific Symposiums to discuss and share novel biological discoveries on cancer, analytical methods and translational approaches using the data. In December 2013, TCGA concluded sample collection, having shipped and processed over 20,000 specimens. By the project’s completion, TCGA published “marker papers” describing

3780-517: Was generated by compiling incidence and survival statistics from the SEER Cancer Statistic website. In addition, U.S. current “Standard of Care” was considered when choosing the top 25 tumor types, as TCGA was targeting tumor types where resection prior to adjunct therapy was the standard of care. Availability of samples also played a critical role in determining which tumor types to study and the order in which tumor projects are started;

3843-580: Was performed under contract by bioinformatics scientists and developers from SRA International , Inc. The DCC did not host raw sequencing data, however. NCI's Cancer Genomics Hub (CGHub) was the secure repository for storing, cataloging, and accessing sequence-related data. This work was performed by scientists and staff at the University of California, Santa Cruz Genomics Institute . Since 2017, all types of data were moved to NCI's Genomic Data Commons. Seven Genome Data Analysis Centers (GDACs) funded by

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3906-550: Was published in 2018 in Science . Brain disease Central nervous system diseases or central nervous system disorders are a group of neurological disorders that affect the structure or function of the brain or spinal cord , which collectively form the central nervous system (CNS). These disorders may be caused by such things as infection, injury, blood clots, age related degeneration, cancer, autoimmune disfunction, and birth defects. The symptoms vary widely, as do

3969-594: Was supervised by the National Cancer Institute 's Center for Cancer Genomics and the National Human Genome Research Institute funded by the US government. A three-year pilot project, begun in 2006, focused on characterization of three types of human cancers: glioblastoma multiforme , lung squamous carcinoma, and ovarian serous adenocarcinoma . In 2009, it expanded into phase II, which planned to complete

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