Mutation -What is that ??

 

Mutations involve changes in the arrangement of the bases that make up a gene. Even a change in just one base among the thousands of bases that make up a gene can have a major effect. A gene mutation can affect the cell in many ways. Some mutations stop a protein from being made at all. A gene mutation is a permanent alteration in the DNA sequence that makes up a gene, such that the sequence differs from what is found in most people. Mutations range in size; they can affect anywhere from a single DNA building block (base pair) to a large segment of a chromosome that includes multiple  DNAs.

 A mutation therefore is a change that occurs in our DNA sequence, either due to mistakes when the DNA is copied or as the result of environmental factors such as UV light and cigarette smoke.

These changes are often caused by perturbed activity of proteins involved in transcriptional control. ... The effects of such mutations are directly attributable to the altered regulation of direct and indirect target genes, as shown extensively for regulation by MYC — a transcription factor often mutated in cancer.

A genome-wide analysis of DNA and RNA sequences, gene expression and DNA modifications in 200 samples of acute myeloid leukaemia sets the stage for data integration and verification that will enhance our understanding of this cancer.

Acute myeloid leukaemia exhibits variable genetics, presentation and clinical outcome. Writing in the New England Journal of Medicine, Ley and colleagues¹ from the Cancer Genome Comprehensive genome-wide analysis of DNA sequences, transcribed messenger RNA and microRNA molecules, and DNA modification by methylation, in 200 cases of adult acute myeloid leukaemia (AML). The data, which are publicly available, provide unprecedented insight into the molecular genetics of this cancer and its influence on treatment responses. Although the challenge of integrating and functionally verifying these data remains, the findings are expected to help to explain the biology of AML, and could lead to the development of therapeutic strategies.

Historically, the identification and characterization of individual genetic modifications, such as chromosomal translocations, gene fusions and gene mutations, have fuelled our understanding of the onset and progression of AML.

More recently, whole-genome and whole-exome sequencing studies have further refined this view, identifying mutations in genes in which they were not expected, such as DNMT3A, IDH1, PHF6 and SMC3. The exome is the portion of the genome comprising exon sequences — those that form mature mRNA molecules.

 Now that our knowledge of DNA-sequence mutations in AML has advanced, it is time for greater integration of this information with data on gene expression.

Deregulation of gene expression is central to cancer development. For example, many cancer-related mutations result in reduced expression of genes that are associated with apoptotic cell death or cell senescence, or alter the expression of genes involved in cell proliferation and differentiation. These changes are often caused by perturbed activity of proteins involved in transcriptional control. Understanding the role of gene expression in cancer will require analysis of epigenetic modifications (structural and chemical genomic changes, such as DNA methylation, that do not change the DNA sequence) and structural changes in chromatin (the complex of DNA and associated histone proteins).