Introduction<br />Genetic mutations are among the most critical factors contributing to the development of many complex diseases, particularly cancer. Understanding how these mutations arise and their impact on cellular function is foundational to advancing prevention and treatment strategies. This article explores the central role of genetic mutations in malignant cellular transformation, highlighting key genes involved and the challenges faced by researchers in this field.<br />1. Definition and Types of Genetic Mutations<br />A genetic mutation is a permanent alteration in the DNA sequence that may affect gene function. Mutations are classified into several types:<br />Point mutations: A single base change in the DNA sequence.<br />Insertions/Deletions: These alter the reading frame of the gene.<br />Chromosomal mutations: Involve larger-scale changes to chromosome structure or number.<br />2. How Do Mutations Lead to Cancer?<br />Cancer arises from the accumulation of mutations that disrupt specific gene functions, particularly:<br />Oncogenes: These are mutated forms of normal proto-oncogenes that promote uncontrolled cell growth.<br />Tumor suppressor genes: Such as TP53, which normally regulate cell division or trigger apoptosis; their inactivation leads to unregulated proliferation.<br />DNA repair genes: Including BRCA1 and BRCA2; mutations in these genes lead to genomic instability.<br />3. Genetic Mutations and Cancer Types<br />Breast cancer: Often linked to mutations in BRCA1/2.<br />Hereditary Nonpolyposis Colorectal Cancer (HNPCC): Caused by mutations in mismatch repair (MMR) genes.<br />Melanoma: Commonly involves mutations in the BRAF gene.<br />Leukemia: Frequently driven by mutations in genes such as FLT3 and NPM1.<br />4. Environmental Factors and Mutation Induction<br />Environmental agents—such as smoking, ultraviolet (UV) radiation, and certain chemicals—can directly damage DNA and trigger mutations that significantly increase the risk of cancer.<br />5. Mutations as Therapeutic Targets<br />Genetic mutations are now used as targets in personalized cancer therapies. Notable examples include:<br />EGFR inhibitors for lung cancer with specific EGFR mutations.<br />PARP inhibitors for patients with BRCA mutations.<br />CAR-T cell therapies targeting leukemia-specific mutations.<br />Conclusion<br />Genetic mutations are key to understanding cancer onset and progression. Advances in genomics and sequencing technologies have paved the way for predictive diagnostics and targeted treatments. Nevertheless, much remains to be learned about the complex interactions between genes and environmental factors in disease development.<br />Huda Rafid Abd Alkhaliq<br />AL_mustaqbal University is the first university in Iraq