A project to classify all somatic mutations in cancer is called the Cancer Genome Project. Exons and surrounding splice junctions of the genomes of primary tumours and malignant cell lines are being comprehensively sequenced as part of this study. The data produced by these experiments is shown using COSMIC software. The CGP had discovered 4,746 genes and 2,985 mutations in 1,848 tumours as of February 2008.
Information on cancer genome, transcriptome, and proteome studies are available from the Cancer Genome Anatomy Project.
An oncogenic reference database called Progenetix provides information about cytogenetic and molecular-cytogenetic tumours. Data from cancer transcriptome profiles have been compiled by Oncomine.
Multidimensional human oncogenic data organised by tumour type is included in the integrative oncogenomics database IntOGen and the Gitools datasets.
IntOGen’s initial version concentrated on the contribution of CNV and dysregulated gene expression to cancer. An updated version focused on the 28 different tumour kinds’ mutational cancer driver genes. The IntOGen database contains all releases of IntOGen data.
The largest initiative to gather information about the human cancer genome is the International Cancer Genome Consortium. The ICGC website provides access to the information. The BioExpress® Oncology Suite includes matched neighbouring controls as well as gene expression data from primary, metastatic, and benign tumour samples as well as normal samples. For several well-known malignancies, the suite includes samples of haematological malignancy.
Genes from the same family have similar roles, as anticipated by similar coding sequences and protein domains, according to the mutational study of whole gene families. The phosphatase family, which removes phosphate groups from proteins, and the kinase family, which add phosphate groups to proteins, are two examples of these classes. Due to their apparent function in transducing cellular signals of cell growth or death, these families were originally studied. For instance, kinase or phosphatase gene mutations are present in more than 50% of colorectal tumours.
Lipid kinases encoded by the phosphoinositol 3-kinases (PIK3CA) gene are frequently mutated in colorectal, breast, gastric, lung, and other malignancies. PIK3CA can be inhibited by medications. Another illustration is the BRAF gene, which was among the first to be linked to melanomas. The RAS-RAF-MAPK growth signalling pathway uses a serine/threonine kinase that is encoded by BRAF. In 59 per cent of melanomas, BRAF mutations result in constitutive phosphorylation and activity. Before BRAF, the genetic basis for melanoma formation was unknown, and patients had a terrible prognosis.
Tumour growth has been associated with alterations in mitochondrial DNA (mtDNA). There are four different kinds of mtDNA mutations known so far:
● Point mutations
Both the coding and non-coding regions of the mtDNA found in cancer cells have been found to have point mutations. The point mutations within the coding area exhibit similarities in patients with lung, head/neck, and bladder malignancies. This implies that the mitochondria appear to become homogenous when a healthy cell undergoes a neoplastic transition into a tumour cell. Numerous point mutations found in the D-loop, a non-coding area of the malignant mitochondria, imply that these mutations may play a significant role in some types of cancer.
Due to its modest size (1kb), this sort of mutation is only rarely encountered. Some evidence that minor mtDNA deletions might develop at the start of carcinogenesis can be seen in the occurrence of certain mtDNA mutations (264-bp deletion and 66-bp deletion in the complex 1 subunit gene ND1) in a variety of cancer types. It also implies that when the tumour develops, there are more mitochondria with these deletions.
The “common deletion,” a rather significant deletion that occurs in many malignancies, is an exception, but normal cells have been discovered to contain more mtDNA large-scale deletions than tumour cells. This might be because tumour cells appear to be adapting by removing any mitochondria that have these sizable deletions (the “common deletion” is > 4kb).
Breast cancer, gastric cancer, hepatocellular carcinoma (HCC), colon cancer, and normal cells can all have two minor mtDNA insertions of 260 and 520 bp. There is no evidence linking these insertions to cancer.
● Copy number mutations
Real-time polymerase chain reaction tests used for mtDNA characterisation reveal that many malignancies have quantifiable changes in mtDNA copy number. Oxidative stress is anticipated to increase in copy number. On the other hand, the decline is assumed to be brought on by somatic point mutations in the p53 (tumour suppressor gene) driven pathway, poor enzyme activity brought on by POLG mutations, and/or the D310 homopolymeric c-stretch in the D-loop region.
The number of copies does not change as a result within tumour cells. Since the amount of mtDNA in tumour cells is constant, a more complex system than aberrant cell growth is likely in charge of regulating the amount of mtDNA in tumour cells. For specific tumour kinds of locales, mtDNA content has a different role in human malignancies.
Some anti-cancer medications have been successful in destroying tumour cells because they target the mtDNA gene. Mitochondrial mutations have been studied as indicators for cancer cell treatment. Because the mitochondrial genome is significantly smaller and thus simpler to test for certain mutations, it is simpler to target mutation in mitochondrial DNA than in nuclear DNA.
Blood sample MtDNA content variations may be used as a screening marker to monitor the development of malignant tumours and predict future cancer susceptibility. MtDNA is crucial for ATP production and maintaining mitochondrial homeostasis in addition to these potentially beneficial properties. It is independent of the cell cycle. Targeting mtDNA is a useful therapeutic approach because of these properties.