A lot of buzz about genomic and genetic testing is heard in oncology. But what are they? Are they the same? How do they differ? Although genetic and genomic do sound similar and are related, the information that each focuses on is different. Adding to the confusion, the terms are sometimes used interchangeably. This article aims to help define the terms and understand how they are used in oncology.
DEFINING THE TERMS
The genome is the complete set of DNA instructions, packaged into two sets of 23 chromosomes per cell, as well as gene-modifying sequences and related information.1 One set of the chromosomes is inherited from the biological mother, and the other set from the biological father. A gene is a part of the genome that carries instructions for making molecules, such as proteins.
Genomics is the study of a set of genes. Mutations in genes, which are changes in their sequences, can be inherited or can arise from changes after birth. Genomics seeks to identify not just gene sequences, but also how they are expressed, how they interact, and how active they are. Both expression and interaction can affect how a condition develops.
Other parts of the genome switch the genes on or off, which allows different tissues to express different genes, even though they all have the same genomic information. The genome is also affected by changes that are not in the actual DNA sequence, but involve adding a chemical, such as a methyl group, to the DNA. These changes, known as the epigenome, affect which proteins are made in which cells.
Genetics is the study of how inherited traits, such as eye color, are passed on. It involves studying a single gene in isolation. When specific genes are altered, the individual risk for a given health condition can be impacted.
Changes that arise in inherited genes that are present in the egg or sperm and affect the offspring are known as germline mutations, such as the BRCA1 and BRCA2 mutations tested for in patients with breast cancer. Changes that arise in nongermline tissues and that are noninheritable are known as somatic mutations. Somatic mutations accumulate in the cells of the body over a person’s lifespan.
Genetic tests in oncology are common. For example, germline mutations in the BRCA1 or BRCA2 genes are a common concern of women with a family history of breast or ovarian cancer. Knowledge of the presence of these mutations may influence a patient’s health care decisions. Recent studies have indicated that preventive oophorectomy may benefit women who carry these genetic mutations, and that a bilateral mastectomy may improve survival for women with these mutations who develop breast cancer.2-3
Breast cancer is not the only area in which testing for inherited conditions guides treatment. Patients with colorectal cancer are screened for genetic markers of Lynch syndrome, which is an inherited familial cancer risk and indicates increased risk for further cancers, as well. Testing for Lynch syndrome is done on DNA isolated from a blood draw or an oral rinse.4
In contrast to inherited genetic risk factors, some genetic testing is done on tumors themselves. These tests seek individual somatic mutations, which are changes in DNA that occur after conception; these mutations are not inherited.
An example of somatic genetic testing is when the tumors of patients with non-small cell lung cancer are tested for changes in genes encoding two tyrosine kinases: epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK).5 Both of these can be targeted by existing drugs: gefitinib and erlotinib for EGFR mutations, and crizotinib for ALK-positive tumors. Testing for these mutations in tumor samples generally involves polymerase chain reaction (PCR)-based tests for EGFR mutations and fluorescent in situ hybridization (FISH) for ALK mutations. These tests examine a single gene for mutations within it, whereas genomic testing examines the interplay of many genes and can include epigenetic changes to the genome.