Cancer is a genetic disease that is, cancer is caused by certain changes to genes that control the way our cells function, especially how they grow and divide.
Genetic changes that promote cancer can be inherited from our parents if the changes are present in germ cells, which are the reproductive cells of the body (eggs and sperm). Such changes, called germline changes, are found in every cell of the offspring. Inherited genetic mutations play a major role in about 5 to 10 percent of all cancers. Researchers have associated mutations in specific genes with more than 50 hereditary cancer syndromes, which are disorders that may predispose individuals to developing certain cancers. Following a diagnosis of the presence of a such certain gene mutation, follow-up counselling is fundamental and clinical management options (such as for patients with BRCA1 and BRCA2 mutations, risk-reducing salpingo-oophorectomy) are available and have been associated with decreased cancer risk and improved mortality.
Cancer-causing genetic changes can also be acquired during one’s lifetime, as the result of errors that occur as cells divide or from exposure to carcinogenic substances that damage DNA, such as certain chemicals in tobacco smoke, and radiation, such as ultraviolet rays from the sun. Genetic changes that occur after conception are called somatic (or acquired) changes.
Solid tumors can be morphologically and biologically heterogeneous, with mutation status differing among patients with the same tumor type, and even within individual tumor samples. In addition, neoplastic tissue can be admixed with benign or necrotic tissue, thereby limiting the sensitivity of certain tests. Tumor enrichment is necessary to ensure reliable results.
The diagnosis and clinical management of patients with cancer is evolving and improving, and new molecular-based tumor classifications and targeted therapies have already been used in routine clinical practice. Incorporation of new molecular markers to traditional diagnostic algorithms is becoming clinically necessary to accurately diagnose and stratify patients with cancer, and geneticist and pathologists are playing a crucial role in developing, validating, and integrating these new diagnostic tests.
Although, tissue biopsies remain the gold standard to assess molecular alterations, this strategy presents several limitations that can impair patient treatment. Indeed, access to tumor tissues is not always optimal.
cfDNA is free-floating DNA present in the blood and other bodily fluids. In addition to its applications in oncology, cfDNA analysis is used extensively for prenatal genetic testing. Researchers have developed assays to detect and quantify tumor DNA in the plasma with high sensitivity and specificity. The application of these assays has shown that plasma DNA and tumor tissue DNA are highly concordant. By liquid biopsy, plasma genotyping has potential clinical utility in early diagnosis, the detection of minimal residual disease (MRD), and the evaluation of treatment response and resistance. In addition to its noninvasive nature, plasma genotyping has several advantages, including longitudinal monitoring, short turnaround time, low cost, and the ability to capture heterogeneity, which is sometimes missed by tissue biopsy, within tumors and between metastatic lesions.
As a sum, genetic and genomic information can help with: