In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosis, or meiosis or other types of damage to DNA, which then may undergo error-prone repair, cause an error during other forms of repair, or cause an error during replication. Mutations may also result from substitution, insertion or deletion of segments of DNA due to mobile genetic elements.
The Wellcome Sanger Institute, previously known as The Sanger Centre and Wellcome Trust Sanger Institute, is a non-profit British genomics and genetics research institute, primarily funded by the Wellcome Trust.
Oncogenomics is a sub-field of genomics that characterizes cancer-associated genes. It focuses on genomic, epigenomic and transcript alterations in cancer.
The Cancer Genome Project is part of the cancer, aging, and somatic mutation research based at the Wellcome Trust Sanger Institute in the United Kingdom. It aims to identify sequence variants/mutations critical in the development of human cancers. Like The Cancer Genome Atlas project within the United States, the Cancer Genome Project represents an effort in the War on Cancer to improve cancer diagnosis, treatment, and prevention through a better understanding of the molecular basis of the disease. The Cancer Genome Project was launched by Michael Stratton in 2000, and Peter Campbell is now the group leader of the project. The project works to combine knowledge of the human genome sequence with high throughput mutation detection techniques.
Serine/threonine kinase 11 (STK11) also known as liver kinase B1 (LKB1) or renal carcinoma antigen NY-REN-19 is a protein kinase that in humans is encoded by the STK11 gene.
DNA polymerase delta catalytic subunit(DPOD1) is an enzyme that is encoded in the human by the POLD1 gene, in the DNA polymerase delta complex. DPOD1 is responsible for synthesizing the lagging strand of DNA, and has also been implicated in some activities at the leading strand. The DPOD1 subunit encodes both DNA polymerizing and exonuclease domains, which provide the protein an important second function in proofreading to ensure replication accuracy during DNA synthesis, and in a number of types of replication-linked DNA repair following DNA damage.
The 1000 Genomes Project (1KGP), taken place from January 2008 to 2015, was an international research effort to establish the most detailed catalogue of human genetic variation at the time. Scientists planned to sequence the genomes of at least one thousand anonymous healthy participants from a number of different ethnic groups within the following three years, using advancements in newly developed technologies. In 2010, the project finished its pilot phase, which was described in detail in a publication in the journal Nature. In 2012, the sequencing of 1092 genomes was announced in a Nature publication. In 2015, two papers in Nature reported results and the completion of the project and opportunities for future research.
Somatic evolution is the accumulation of mutations and epimutations in somatic cells during a lifetime, and the effects of those mutations and epimutations on the fitness of those cells. This evolutionary process has first been shown by the studies of Bert Vogelstein in colon cancer. Somatic evolution is important in the process of aging as well as the development of some diseases, including cancer.
Cancer genome sequencing is the whole genome sequencing of a single, homogeneous or heterogeneous group of cancer cells. It is a biochemical laboratory method for the characterization and identification of the DNA or RNA sequences of cancer cell(s).
DECIPHER is a web-based resource and database of genomic variation data from analysis of patient DNA. It documents submicroscopic chromosome abnormalities and pathogenic sequence variants, from over 25000 patients and maps them to the human genome using Ensembl or UCSC Genome Browser. In addition it catalogues the clinical characteristics from each patient and maintains a database of microdeletion/duplication syndromes, together with links to relevant scientific reports and support groups.
Sir Michael Rudolf Stratton is a British clinical scientist and the third director of the Wellcome Trust Sanger Institute. He currently heads the Cancer Genome Project and is a leader of the International Cancer Genome Consortium.
Cancer systems biology encompasses the application of systems biology approaches to cancer research, in order to study the disease as a complex adaptive system with emerging properties at multiple biological scales. Cancer systems biology represents the application of systems biology approaches to the analysis of how the intracellular networks of normal cells are perturbed during carcinogenesis to develop effective predictive models that can assist scientists and clinicians in the validations of new therapies and drugs. Tumours are characterized by genomic and epigenetic instability that alters the functions of many different molecules and networks in a single cell as well as altering the interactions with the local environment. Cancer systems biology approaches, therefore, are based on the use of computational and mathematical methods to decipher the complexity in tumorigenesis as well as cancer heterogeneity.
Tumour heterogeneity describes the observation that different tumour cells can show distinct morphological and phenotypic profiles, including cellular morphology, gene expression, metabolism, motility, proliferation, and metastatic potential. This phenomenon occurs both between tumours and within tumours. A minimal level of intra-tumour heterogeneity is a simple consequence of the imperfection of DNA replication: whenever a cell divides, a few mutations are acquired—leading to a diverse population of cancer cells. The heterogeneity of cancer cells introduces significant challenges in designing effective treatment strategies. However, research into understanding and characterizing heterogeneity can allow for a better understanding of the causes and progression of disease. In turn, this has the potential to guide the creation of more refined treatment strategies that incorporate knowledge of heterogeneity to yield higher efficacy.
The Network of Cancer Genes (NCG) is a freely accessible web resource of genes that, when altered in their sequence, drive clonal expansion of normal tissues or cancer. The project was launched in 2010 and has reached its 7th release in 2022. In 2023 the additional annotation of cancer drivers that interact with the tumour immune microenvironment was added. NCG7.1 reports information on 3,347 cancer drivers and 95 healthy drivers. Of these, 596 are also TIME drivers. NCG7.1 also reports the system-level properties and the associated publications of each driver, as well as a list possible false positives. NCG7.1 enables advanced searches on the primary anatomical site, cancer type, type of sequencing screens and literature supports.
The human interactome is the set of protein–protein interactions that occur in human cells. The sequencing of reference genomes, in particular the Human Genome Project, has revolutionized human genetics, molecular biology, and clinical medicine. Genome-wide association study results have led to the association of genes with most Mendelian disorders, and over 140 000 germline mutations have been associated with at least one genetic disease. However, it became apparent that inherent to these studies is an emphasis on clinical outcome rather than a comprehensive understanding of human disease; indeed to date the most significant contributions of GWAS have been restricted to the “low-hanging fruit” of direct single mutation disorders, prompting a systems biology approach to genomic analysis. The connection between genotype and phenotype remain elusive, especially in the context of multigenic complex traits and cancer. To assign functional context to genotypic changes, much of recent research efforts have been devoted to the mapping of the networks formed by interactions of cellular and genetic components in humans, as well as how these networks are altered by genetic and somatic disease.
Mutational signatures are characteristic combinations of mutation types arising from specific mutagenesis processes such as DNA replication infidelity, exogenous and endogenous genotoxin exposures, defective DNA repair pathways, and DNA enzymatic editing.
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.
Cancer pharmacogenomics is the study of how variances in the genome influences an individual’s response to different cancer drug treatments. It is a subset of the broader field of pharmacogenomics, which is the area of study aimed at understanding how genetic variants influence drug efficacy and toxicity.
Serena Nik-Zainal is a British-Malaysian clinician who is a consultant in clinical genetics and Cancer Research UK advanced clinician scientist at the University of Cambridge. She makes use of genomics for clinical applications. She was awarded the Crick Lecture by the Royal Society in 2021. Serena Nik-Zainal was also recognized as one of the 100 Influential Women in Oncology by OncoDaily.
Michael Scott Lawrence is an American geneticist best known for his work on mutational signatures. Lawrence is an assistant professor of pathology at the Harvard Medical School, Assistant Geneticist at the Massachusetts General Hospital, and member of the Broad Institute.
