From the Guidelines
The primary types of oncologic mutations, besides somatic mutations, include germline mutations, epigenetic alterations, and chromosomal abnormalities. Germline mutations are inherited genetic changes present in reproductive cells that can be passed from parents to offspring, predisposing individuals to cancer syndromes such as BRCA1/2 mutations in hereditary breast and ovarian cancer or Lynch syndrome in colorectal cancer 1. Epigenetic alterations involve changes in gene expression without altering the DNA sequence itself, including DNA methylation, histone modifications, and chromatin remodeling, which can silence tumor suppressor genes or activate oncogenes. Chromosomal abnormalities encompass large-scale changes like translocations (such as the Philadelphia chromosome in chronic myeloid leukemia), deletions, duplications, and aneuploidy (abnormal chromosome numbers).
Some key points to consider:
- Germline mutations can be identified through sequencing of germline DNA, and this testing should be done at the time of initial diagnosis for individuals with ovarian cancer 1.
- Somatic mutations can be identified through tumor sequencing, but this method cannot distinguish between tumor-specific somatic mutations and patient’s germline variants without a paired normal sample 1.
- The classification of oncogenicity of somatic variants is crucial for precision oncology, and a standardized approach should be used to classify these variants 1.
- Understanding the different types of oncologic mutations is essential for developing comprehensive cancer prevention strategies and personalized treatment approaches based on the specific genetic profile of each patient's cancer.
It is essential to note that the implications of the same variant in germline and somatic context could be different, and some variants in hereditary cancer genes may be present as germline, but not as somatic and vice versa 1. Therefore, a comprehensive approach to genetic testing and counseling is necessary to identify individuals with germline mutations and to provide appropriate risk assessment and management.
From the Research
Types of Oncologic Mutations
- Somatic mutations: These are acquired genetic mutations that form under the influence of environmental factors during embryo formation and epigenetic development 2. They are not present in every cell of the body and can be used to find targeted drugs, monitor tumor loading for guided therapy, and evaluate prognosis.
- Germline mutations: These are congenital genetic mutations in germ cells that originate from sperm or ovum and are generally incorporated into every cell of the offspring's body 2. Germline mutations are closely related to the occurrence, development, and prognosis of diseases, and can be used to determine inherited malignancies and identify high-risk families.
Other Key Points
- The detection of somatic and germline mutations can be used to recommend precision-medicine therapeutics, with a success rate of 91.6% for patients with formalin-fixed, paraffin-embedded tumors (FFPE samples) 3.
- BRCA1 and BRCA2 mutations confer increased risk for development of breast cancer, and are associated with distinct somatic genetic changes during tumor progression 4, 5.
- Secondary BRCA1 and BRCA2 alterations can lead to acquired chemoresistance in tumors carrying frame-shift BRCA1/2 mutations 6.