lect 30 n 31 Mutation Detection in Solid Tumours - Vocabulary Review

Comprehensive vocabulary flashcards based on the lecture on solid tumour mutation detection, covering cancer diagnostics, specific mutations (BRAF, EGFR), immunotherapy, and laboratory methods.

Cancer

A malignant tumour characterized by uncontrolled cell division and the ability to invade adjacent tissue (invasion) or migrate to distant sites (metastasis).

Invasion

The direct growth of transformed cancer cells into adjacent tissues.

Metastasis

The migration of cancer cells from the primary site to distant sites in the body.

Differential Diagnosis

The use of mutation testing to indicate a particular diagnosis when histology or immunohistochemical stains are not definitive, such as identify a $c-KIT$ mutation to diagnose GIST.

Prognosis

The predicted outcome or survival rate of a patient based on the presence of specific markers, such as $IDH1/IDH2$ mutations in brain tumours.

Targeted Cancer Therapies

Treatments that rely on the presence or absence of specific mutations in tumour cells to inhibit mutant receptors or signalling molecules.

$EGFR$ Tyrosine Kinase Inhibitors ($EGFR$ TKIs)

Drugs used in lung cancer treatment for patients with activating $EGFR$ mutations; examples include gefitinib and erlotinib.

$$EGFR_{T790M}$$

A specific mutation in lung cancer that mediates resistance to $1^{st}$ and $2^{nd}$ generation $EGFR$ TKIs but remains sensitive to $3^{rd}$ generation inhibitors like osimertinib.

Disease Monitoring

The detection of tumour-specific DNA mutations in circulation (blood) to indicate treatment response or predict relapse.

Next Generation Sequencing (NGS)

A high-throughput DNA sequencing technology used to identify single mutations, whole genome profiles, or actionable clinical mutations.

Tumour Mutation Burden (TMB)

Molecular marker representing the total number of mutations per megabase; high TMB ($TMB-H$) is defined as $> 10$ mutations per megabase.

Microsatellites

Short DNA segments ($1-6\,bp$) consecutively repeated throughout the genome which are prone to errors during replication.

MMR Enzymes

Mismatch Repair enzymes (e.g., $MLH1$, $PMS2$, $MSH2$, $MSH6$) that act as heterodimers to detect and repair errors in nucleotide repeats.

Microsatellite Instability (MSI)

A condition caused by the inactivation of MMR enzymes, leading to a high mutation burden and increased susceptibility to immunotherapies.

Immune Checkpoints

Normal immune system components (e.g., $PD-1/PD-L1$, $CTLA4$) that act as switches to turn off immune reactions and prevent destruction of normal cells.

Checkpoint Inhibitors

A type of immunotherapy that reactivates immune responses against cancer by blocking the 'inhibitor' signals used by tumour cells to evade the immune system.

Small Molecule Inhibitors

Targeted drugs that typically end in the suffix '-ib' (e.g., imatinib, vemurafenib).

Antibodies

Targeted drugs or immunotherapies that typically end in the suffix '-ab' (e.g., trastuzumab, nivolumab).

$$BRAF_{V600E}$$

A common mutation found in approximately $40-50\%$ of cutaneous melanomas that indicates sensitivity to $BRAF$ inhibitors.

Small Cell Lung Cancer (SCLC)

A subtype comprising $~15\%$ of lung cancers, strongly associated with smoking and nearly universal mutations in $TP53$ and $RB1$.

Non-Small Cell Lung Cancer (NSCLC)

The most common lung cancer subtype ($~85\%$), including adenocarcinomas and squamous cell carcinomas, often tested for actionable mutations like $EGFR$ or $ALK1$.

Osimertinib (Tagrisso)

A $3^{rd}$ generation $EGFR$ TKI used to treat patients who have developed the $EGFR_{T790M}$ resistance mutation.

Formalin-Fixed Paraffin-Embedded (FFPE)

The routine processing method for solid tumour pathology specimens, providing excellent preservation and long-term stability for molecular testing.

Fixatives

Chemicals like $4\%$ buffered formalin that crosslink proteins to preserve tissue structure and prevent enzymatic degradation.

Variant Allele Frequency (VAF)

The proportion of a specific mutant DNA sequence relative to the total DNA in a sample, used to assess the presence of mutations in heterogeneous tumours.

Clonal Evolution

The process by which cancer cells acquire new mutations over time, leading to subpopulations of cells with survival advantages and genetic heterogeneity.

RCPAQAP

Royal College of Pathologists of Australasia Quality Assurance Programmes, which provide external quality assurance testing for pathology laboratories.