Genomic testing identifies germline or inherited DNA changes that increase a person’s cancer risk, and it also can identify or profile the somatic or acquired changes in a tumor that guide selection of appropriate targeted therapies. The latter type of genomic testing is an analysis of DNA sequence information.
DNA sequencing determines the order of the nucleotides or base pairs that make up a DNA molecule. Humans are 99.9% identical in DNA sequence; it is the 0.1% variation that accounts for differences in disease risk from one human to another.
Rapid advancements in DNA sequencing technology and bioinformatics (i.e., the ability to store and analyze large databases of genomic material) have enabled us to identify and catalogue DNA variations and determine which variants (i.e., changes in DNA sequence, also known as mutations) are associated with increased risk for disease. DNA sequencing can be done on a single gene; however, oncology is now in an era dominated by next-generation sequencing (NGS) and whole-genome sequencing (WGS). With NGS, a large array of genes can be tested at the same time in a single diagnostic platform.
What Is the Difference Between the Techniques?
Think of DNA as letters of the alphabet. Letters are arranged to make words, sentences, chapters, and entire books. Genes are defined as DNA that is functionally active or that codes for a protein, but most elements of human DNA are considered non-coding. Non-coding DNA (not a gene) still has important regulatory functions and may affect the expression and regulation of nearby genes (coding DNA). The techniques differ based on how much DNA is sequenced.
- The entire book: Sequences each of the approximately 3 billion base pairs, including all non-coding regions. This is known as WGS.
- A few sentences in each chapter: Only sequences the coding regions of a person’s genome (the exons). This is known as whole-exome sequencing (WES) and represents about 2% of a person’s total DNA.
- A paragraph or even a single line of text: This is known as targeted DNA sequencing and is used for known pathogenic variants. Targeted sequencing can look for those variants in a single gene (e.g., BRCA) or multiple genes (analyzed simultaneously with NGS), such as with multigene panels.
The disadvantage of sequencing methods is that they don’t necessarily detect large-scale DNA deletions or duplications, which is like a book missing an entire chapter. Those types of DNA changes are detected using non-sequencing technologies.
Many laboratories offer genomic testing, but not all laboratories are created equal. Those doing DNA sequencing must adhere to the American College of Medical Genetics and Genomics laboratory standards and guidelines.
Until the implications of all DNA variations have been described (e.g., benign variations, variations that contributes to disease risk), WGS will unlikely be employed for all patients because clinical utility is uncertain. However, that time is coming and oncology nurses must keep pace with the rapid developments in and clinical applications of genomics.
Oncology nurses have always mastered complex and technical scientific knowledge to accurately disseminate and guide patients and families. In this era of precision and genomic-guided oncology, the need to be proficient and literate in genomic content and concepts is essential and will become as commonplace as interpreting a complete blood count or calculating an absolute neutrophil count.