Glossary

Acquired resistance

Clinical scenario in which a cancer that has initially responded to therapy relapses or progresses over time

ALK

Also known as anaplastic lymphoma kinase, it is a protein involved in cell growth

AMP

Also known as anchor multiplex PCR, it is a form of targeted NGS that allows detection of gene rearrangements from low nucleic acid input sourced from formalin-fixed paraffin-embedded specimens

Antigen

A foreign substance that induces an immune response in the body

Archer fusion

A targeted sequencing technology, it requires a single read spanning two separate genes to be considered a fusion candidate

Basket trial

A clinical trial in which patients are grouped primarily by genetic mutations that drive disease rather than by the disease site or histology

BDGF

Also known as brain-derived growth factor, it is a member of the neutrophin family of growth factors

Break-apart assay

Break-apart probes target two areas of a specific gene sequence

Breakthrough therapy

United States Food and Drug Administration designation that expedites drug development based on preliminary clinical evidence indicating that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints

Chimeric oncoprotein

A protein generated by the chromosome translocation of two genes in which the functional domains of two separate genes are fused together

Chromosomal rearrangement

A chromosome abnormality involving a change in the structure of the native chromosome

ctDNA

Also referred to as circulating tumour DNA, it is fragmented DNA derived from tumours that circulates in the bloodstream that is not associated with cells

Dimerisation

When two monomers join to form a dimer

Driver genetic alteration

Genetic changes that disrupt normal cellular processes and contribute to the initiation and progression of the malignant phenotype

Epitope

The part of an antigen that the antibody attaches itself to

Exon

DNA or RNA segment containing information coding for a protein or peptide sequence

Exosome

Extracellular vesicles that are produced in the endosomal compartment of most eukaryotic cells

FISH

Also known as fluorescence in situ hybridisation, it detects gene rearrangements in RNA/DNA that may generate a fusion transcript

Fusion protein

A protein created by the joining of two or more genes that originally coded for separate proteins

Gene fusion rearrangements

Process by which the complete or partial sequences of two or more distinct genes are fused into a single gene or transcript

Genetic profiling

The analysis of DNA samples from an individual

Genomics

The study of genes and their functions, and related techniques

IC50

The half maximal inhibitory concentration, which is a measure of the potency of a substance in inhibiting a specific biological or biochemical function

High-prevalence tumours

Tumours with a high likelihood of NTRK gene rearrangements. These include tumours with certain histologies or specific molecular subgroups, such as pan-negative lung adenocarcinoma, wild-type and MSI-high colorectal carcinomas, IDH1 wild-type gliomas, pan-negative GIST and CD34-positive fibrosarcoma of soft tissue and bone.

IHC

Also known as immunohistochemistry, it detects protein expression which may be attributable to a fusion event

Integrative Genomics Viewer

A visualisation tool that allows for real-time exploration of genomics data

Intron

A segment of DNA or RNA that does not code for proteins and interrupts the sequence of genes

Kinase domain

A structurally conserved region of protein kinases that contains the catalytic function of these enzymes

Low-prevalence tumours

Tumours with a low likelihood of NTRK gene rearrangements

MAPK

Also known as mitogen-activated protein kinase, this is a family of serine/threonine protein kinases involved in cellular functions such as proliferation, differentiation, apoptosis, and survival

Microsatellite instability

Predisposition to genetic mutation resulting from impaired DNA mismatch repair

Mismatch repair

DNA repair system in which one member of a mismatched pair of bases is converted to the normally matched base

Molecular tumour board

Multidisciplinary panel that provides opinion on the clinical implications of molecular pathology test results of patient tumours

Multiplex

To allow large expansion of the number of targets and throughput of diagnostic testing

Multikinase inhibitor

A small-molecule inhibitor of several kinases with potential antineoplastic activity

Nested RT-PCR

Also known as nested polymerase chain reaction, it is a form of PCR that reduces non-specific binding due to amplification of unexpected primer binding sites

Neutrophin

A family of proteins that signal cell survival, differentiation, growth cessation, and apoptosis, which involves binding to two classes cell surface receptors, one of which are TRKs

NGF

Also known as nerve growth factor, it is a neurotrophic factor and neuropeptide involved in the regulation of growth, maintenance, proliferation, and survival of neurons

NGS

Also known as next-generation sequencing, it detects known and novel fusions with breakpoints in DNA or RNA

NTRK gene

Gene coding for the neurotrophic receptor tyrosine kinase

NTRK gene fusion

Targetable driver genetic alterations that code for aberrant fusion proteins and drive tumourigenesis; these are formed by joining of the 3’ region of the NTRK gene, including the kinase domain, with the 5’ region of a different gene (i.e. the fusion partner) by intra- or inter-chromosomal rearrangement

Ommaya

An intraventricular catheter system used for aspiration of cerebrospinal fluid

Oncogenic driver

A genomic alteration that confers a selective growth advantage

Orphan drug

A pharmaceutical agent that has been developed specifically to treat a rare medical condition

PI3K

Also known as phosphoinositide 3-kinase, this enzyme is involved in signal transduction and controls cell growth and other cell functions, including cell survival

PKC

Also known as protein kinase C, this family of protein kinases controls the function of other proteins via phosphorylation of serine and threonine amino acid residues

Plasticity

Adaptability to environmental changes

Point mutation

Mutation affecting only one or very few nucleotides in a gene sequence

Precision medicine

Medical care that optimises the efficiency or therapeutic benefit for particular patients, particularly through the use genetic or molecular profiling

Primers

Short single strand of RNA or DNA that serves as a starting point for DNA synthesis

Proliferation assay

Assays typically used to measure the rate of DNA replication, analyse metabolic activity, and determine cell surface antigen recognitions

ROS1

A receptor tyrosine kinase with structural similarity to the anaplastic lymphoma kinase protein, its activation can lead to aberrant stimulation of signal transduction pathways

RT-PCR

Also known as reverse-transcriptase polymerase chain reaction, it can be used to detect known fusion transcripts in RNA

Sensitivity

Ability of a test to correctly identify those with the disease

Solvent-front substitution

Mutations involving the kinase solvent front of driver kinases and associated with resistance to kinase inhibitor therapies

Somatic

Referring to cells of the body rather than germ-line cells

Specificity

Ability of a test to correctly identify those without the disease

Transcript

Length of RNA or DNA that has been transcribed from a DNA or RNA template, respectively

Transcription

Process in which a single strand of DNA is copied into a molecular of mRNA

Translation

Process in which mRNA is decoded to produce a specific amino acid chain (protein)

TRK fusion cancers

Group of cancers that are caused in part by the presence of NTRK gene fusions

TRK fusion protein

The protein product of NTRK gene fusions, these proteins are constitutively active and result in cell growth, proliferation, and survival pathway activation

TRK inhibitors

A type of tyrosine kinase inhibitor and a type of targeted therapy against TRK fusion proteins

TRK receptors

Also known as tropomyosin receptor kinase receptor, these are a family of tyrosine kinases that regulates synaptic strength and plasticity in the mammalian nervous system

Tumour-agnostic treatment

A drug treatment that is used to treat any kind of cancer, regardless of where in the body or what tissue it initiated from

Tyrosine kinase

An enzyme that can transfer a phosphate group from ATP to a protein in a cell, it plays a critical activation and deactivation role in many cellular functions

Tyrosine kinase inhibitor

Substance that blocks the action of tyrosine kinases

Whole transcriptome sequencing

The use of next-generation sequencing (NGS) to reveal the presence and quantity of RNA in a biological sample

Xenograft

Transplant of an organ, tissue, or cells to an individual of another species

xDFG motif substitution

Mutations involving the xDFG motif of driver kinases and associated with resistance to kinase inhibitor therapies