Cancer Biomarker Report Terms


Summary: This resource explains common terms used in cancer biomarker test reports. 

By Clinical Education at JAX | January 2024

Genomic test results using DNA extracted from tumor tissue frequently demonstrate a complex molecular signature that is different from that of normal tissue for any given patient. Test results provide a synopsis of the genomic variants that have been identified and categorized by potential actionability with regard to treatment options.

Types of genomic alterations/changes reported

Somatic or acquired variants arise in cancers and alter the normal sequence pattern of DNA. They occur when cells are damaged during replication, by viruses or by exposure to carcinogens, such as tobacco smoke or radiation.


Type of variant



Point Mutation

Single nucleotide variant (SNV) or nucleotide change

Substitution, deletion, duplication, insertions, or a combination 

BRAF V600E (substitution)


Copy number variant (CNV)

change in the number of copies of a cancer-related gene

ERBB2 Amplification (copy number gain)


Structural rearrangement

May include chromosome translocations, deletions, duplication, or inversions

EML4-ALK recurrent inversion mutation in non-small cell lung cancer


Reporting the impact of genomic variants

Variants may or may not have an impact on the function of the gene. Genomic variations that do impact function may be activating, resulting in a gain of function of the protein, or inactivating, resulting in a loss of function.1  The significance of the change depends on the location of the variant, the type of genetic aberration, and the normal function of the protein.

 Genomic variants are classified into three general categories:

  • Benign or likely benign: variants do not have any functional consequences and are often seen commonly in the general population. You may also see these referred to as “polymorphisms.”
  • Pathogenic or likely pathogenic: variants impact the function of the gene in some way. Most accurately, these are referred to as “variants that impact function”. More commonly, these may be referred to as “mutations.”
  • Variants of unknown significance or VUS are changes in the gene for which the impact is unknown. This may be because they are rare and there is not enough data available to be conclusive about their functional impact. Over time, VUS are likely to be re-classified as benign or pathogenic as more data are amassed.

Genomic variant nomenclature

The combination of numbers and letters provides a variant’s location, type of aberration and protein change.


“c.” prefix denotes standard variant nomenclature based on coding DNA reference sequences 

“p.” prefix denotes standard variant nomenclature based on protein-level amino acid sequences

Other common biomarkers

PARP inhibition biomarkers

  • Homologous recombination repair deficiency (HRD): A measure of genomic instability that results from defects in the ability of cells to repair double-strand DNA breaks through the homologous recombination pathway. This can include analysis of BRCA1 and BRCA2 and loss of heterozygosity (LOH). A high HRD score is associated with potential sensitivity to platinum-based chemotherapy and PARP inhibitors in some cancer types.
  • Loss of heterozygosity (LOH): A measure of genomic instability that results from the loss of one copy of a gene or chromosomal region. This can be caused by defective homologous recombination repair mechanisms. A high level of LOH is associated with potential sensitivity to platinum-based chemotherapy and PARP inhibitors in some cancer types.

Immunotherapy biomarkers

  • Microsatellite Instability (MSI): A measure of genomic instability that results from defects in the DNA mismatch repair (MMR) system. High MSI is associated with a better response to immunotherapy in some cancer types. Reported as: high (MSI-H) or stable (MSS)
  • Mismatch Repair deficiency (MMR): A measure of genomic instability that results from variants in the genes that code for MMR proteins (MLH1, MSH2, MSH6, PMS2) and causes microsatellite instability (MSI). These variants can be inherited or acquired during an individual's lifetime.Reported as: proficient or deficient
  • PD-L1 (programmed death ligand-1): A protein that is associated with immune system suppression. Positive PD-L1 immunohistochemistry (IHC) has been associated with response to immunotherapy in some cancer types.Reported as: Tumor proportion score (TPS), Tumor Cell Expression (%), Combined positive score (CPS), Tumor cell (TC) score (%), or Tumor-infiltrating immune cell (IC) score (%)
  • Tumor mutational burden (TMB): A measure of the number of mutations present in tumor tissue or in circulating tumor DNA. High TMB is associated with improved response to immunotherapy.Reported as: number of mutations per megabase of DNA analyzed

Learn More

Exploring Cancer Biomarker Testing (CME|CNE). Learn about benefits, limitations, and challenges of using large biomarker tests.

Interpreting Cancer Biomarker Testing - When is Additional Testing Needed? (CME|CNE). Learn when additional cancer biomarker testing is indicated for further evaluation of genome-informed therapy.

Ordering & Interpreting PD-L1 testing. Discusses which patients may benefit from PD-L1 testing and how to select and interpret tests for patients with different cancer types.

PARP Inhibitors: Overview and Indications. Discusses FDA-approved indications for PARPi for maintenance therapy and cancer treatment.

Sequence Variant Nomenclature. Provides recommendations for the description of sequence variants. Nomenclature authorized by Human Genome Variation Society (HGVS), Human Variome Project (HVP), and the HUman Genome Organization (HUGO).

Types of Molecular Tumor Testing. Describes different types of genomic variants/alterations and testing methodology.


1. Li MM, Datto M, Duncavage EJ, Kulkarni S, Lindeman NI, Roy S, et al. Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists. J Mol Diagn. 2017;19(1):4-23.


All information in this resource is provided for educational purposes only.