Letter to the Editor
Patricia A. Kelly, DNP, APRN, CNS, AGN-BC, AOCN®, Kathleen Calzone, PhD, RN, AGN-BC, FAAN, Patricia Friend, PhD, APRN-CNS, AOCNS®, AGN-BC, and Suzanne M. Mahon DNS RN AOCN® AGN-BC FAAN
We read with interest the April 2022 JADPRO meeting report article, “Molecular Testing in Hematologic Malignancies”, as presented by Laura Zitella, MS, RN, ACNP-BC, AOCN®. We were pleased that Ms. Zitella chose to share information about biomarker testing, a topic that is frequently not addressed nor well understood by advanced practitioners. We would however like to call attention to a significant error in describing nonsense variants and highlight a transition in using the term “variant” to replace “mutation”.
Beth Faiman, PhD, MSN, APRN-BC, AOCN®, BMTCN, FAAN
Dear Dr. Faiman,
We read with interest the April 2022 JADPRO meeting report article, “Molecular Testing in Hematologic Malignancies”, as presented by Laura Zitella, MS, RN, ACNP-BC, AOCN®. We were pleased that Ms. Zitella chose to share information about biomarker testing, a topic that is frequently not addressed nor well understood by advanced practitioners. We would however like to call attention to a significant error in describing nonsense variants and highlight a transition in using the term “variant” to replace “mutation.”
In the meeting report, Ms. Zitella states that a nonsense mutation “does not have any significant consequences because an abnormal protein is not made” (Zitella, 2022, p. 326). According to the National Cancer Institute Dictionary of Genetic Terms, “a nonsense variant is a genetic alteration that causes the premature termination of a protein. The altered protein may be partially or completely inactivated, resulting in a change or loss of protein function.” (https://www.cancer.gov/publications/dictionaries/genetics-dictionary/). Similar definitions are found in the National Human Genome Research Institute Talking Glossary of Genomic and Genetic Terms (https://www.genome.gov/genetics-glossary and the Oncology Nursing Society Genomics Taxonomy (https://www.ons.org/genomics-taxonomy/variant). It is noteworthy that approximately 11.3% of all diseases are associated with nonsense variants (Abrahams et al., 2021).
Secondly, variant is the preferred terminology when referring to a change in the DNA sequence (formerly designated as mutation or as polymorphism). The American College of Medical Genetics and Genomics introduced this change to avoid confusion and incorrect assumptions that mutations are always pathogenic, i.e., causing a medical condition (Richards et al., 2015). Overall, changes in the DNA sequence “can be harmful, beneficial, or neutral in their effect on cell function” (https://www.cancer.gov/publications/dictionaries/genetics-dictionary/). One example of variant terminology in clinical practice is genetic testing reports. Variants are reported according to five classifications established by specific criteria: benign, likely benign, uncertain, likely pathogenic, and pathogenic (East, et al., n.d.; Richards et al., 2015). The Oncology Nursing Society (ONS) has adopted the change to variant terminology as reflected in the “Genomics Taxonomy” https://www.ons.org/genomics-taxonomy/variant and the ONS “Call to Action” (n.d.).
Improving genomic literacy is a critical first step in actualizing genomics-informed care. Consistent and accurate genomics terminology matters when delivering safe and quality cancer care (Friend et al., 2021; Oncology Nursing Society, n.d.).
Patricia A. Kelly, DNP, APRN, CNS, AGN-BC, AOCN®
Kathleen Calzone, PhD, RN, AGN-BC, FAAN
Patricia Friend PhD, APRN-CNS, AOCNS®, AGN-BC
Suzanne M. Mahon DNS RN AOCN® AGN-BC FAAN
Abrahams, L., Savisaar, R., Mordstein, C., Young, B., Kudla, G., & Hurst, L. D. (2021). Evidence in disease and non-disease contexts that nonsense mutations cause altered splicing via motif disruption. Nucleic Acids Research, 49(17), 9665–9685. https://doi.org/10.1093/nar/gkab750
East, K., et al & Clinical Sequence Exploratory Research (CSER) Consortium. (n.d.) Guide to Interpreting Genomic Reports: A Genomics Toolkit, https://www.genome.gov/sites/default/files/media/files/2020-04/Guide_to_Interpreting_Genomic_Reports_Toolkit.pdf
Friend, P., Dickman, E., & Calzone, K. (2021). Using a genomics taxonomy: Facilitating patient care safety and quality in the era of precision oncology. Clinical Journal of Oncology Nursing, 25(2), 205–209. https://doi.org/10.1188/21.CJON.205-209Friend
National Cancer Institute. (n.d.), Dictionary of Genetic Terms. https://www.cancer.gov/publications/dictionaries/genetics-dictionary/
National Human Genome Research Institute. (n.d.) Talking Glossary of Genomic and Genetic Terms. https://www.genome.gov/genetics-glossary
Oncology Nursing Society (n.d.) Genomics Taxonomy. https://www.ons.org/genomics-taxonomy/variant
Oncology Nursing Society (n.d.) Oncology Nursing Society Call to Action: Using the Appropriate Genomic Terminology for Safety and Quality, ONS_Genomics_Terminology_Call_to_Action.pdf
Richards, S., Aziz, N., Bale, S., Bick, D., Das, S., Gastier-Foster, J., Grody, W. W., Hegde, M., Lyon, E., Spector, E., Voelkerding, K., Rehm, H. L., & ACMG Laboratory Quality Assurance Committee (2015). Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genetics in Medicine,17(5), 405–424. https://doi.org/10.1038/gim.2015.30
Zitella L. J. (2022). Molecular testing in hematologic malignancies. Journal of the Advanced Practitioner in Oncology, 13(3), 324–327. https://doi.org/10.6004/jadpro.2022.13.3.29