Mutation

A mutation is a permanent alteration in the DNA sequence of a gene, chromosome, or genome. Mutations can affect a single nucleotide or involve large segments of DNA, and they are fundamental drivers of genetic diversity, evolution, and many diseases, including cancer.

• Point mutation – A change in a single nucleotide.
  • *Missense*: Changes the amino acid.
  • *Nonsense*: Introduces a premature stop codon.
  • *Silent*: Does not change the amino acid.
• Frameshift mutation – Insertion or deletion (indel) of nucleotides that disrupts the reading frame.
• Splice-site mutation – Alters the normal splicing of exons and introns.
• Insertion/Deletion (indel) – Addition or loss of nucleotides.
• Copy number variation (CNV) – Duplication or deletion of gene regions.
• Chromosomal rearrangement – Inversions, translocations, or duplications of chromosomal segments.

• Loss of function – Common in tumor suppressor genes (e.g., *TP53*, *NF2*).
• Gain of function – Leads to new or increased activity (e.g., *EGFR* mutations).
• Dominant-negative – Mutated protein interferes with the normal version.
• Neutral – No significant impact on protein function.

• Sanger sequencing
• Next-Generation Sequencing (NGS)
• qPCR or digital PCR
• FISH (for large rearrangements)

• gene
• genetic_variation
• somatic_mutation
• germline_mutation
• dna_repair