4
Key Points
Table 1. Select Definitions of Commonly Used Terms in
Precision Oncology
Term Definition
Homologous
recombination
deficiency (HRD)
Cells that cannot efficiently repair damaged DNA via
homologous recombination.
The companion diagnostic for niraparib defines HRD-positive
as detection of deleterious or suspected deleterious mutations
within BRCA1 or BRCA2 or a positive GIS.
Immunotherapy A type of therapy that activates the body's immune system to
target cancer cells.
Intertumoral
heterogeneity
The evolution of tumor cells over time so that the genomic
profile differs between the primary and the metastatic sites and/
or amongst multiple metastatic lesions.
Intratumoral
heterogeneity (ITH)
Within the same tumor, different populations of cells within
distinct spatial regions have unique genomic alterations.
Multigene panel A next-generation sequencing (NGS) test that sequences a
defined list of genes with at least 50 genes in total.
Mutation A change in the nucleotide sequence encoding for a gene.
Mutational
signature
Combination of mutations that are characteristic of a specific
mutagenesis process leading to or contributing to the disease.
Minimal residual
disease (MRD)
e presence of tumor cells that have spread from the primary
tumor but are not detectable by imaging.
Microsatellite
instability (MSI)
e presence of nucleotide insertions or deletions at
microsatellite loci, which indicates a deficiency in the mismatch
repair machinery that normally corrects these errors.
• Microsatellites: Highly polymorphic, short, tandem repeats
of DNA nucleotides distributed throughout the human
genome, prone to replication errors.
• Microsatellite instability-high (MSI-H): The presence of a
high level of mutations at the sequenced microsatellite loci.
Mismatch repair
deficiency (dMMR)
e loss of function or expression of one or more of the
components of the dMMR (typically PMS2, MLH1, MSH2,
and MSH6) that recognize mismatches within DNA as a result
of injury and initiate the repair process.
LOH e loss of the wildtype allele of a gene that was previously in
a heterozygous state due to a germline or somatic mutation.
LOH can occur at a single gene or as a genome-wide event
due to defective DNA repair and be indicative of homologous
recombination deficiency.
(cont'd)
