Molecular reference standards

Molecular/Genomic reference standards are a class of ‘controls’ or standards used to check the performance of molecular diagnostic assays. Molecular/Genomic Reference Materials (RMs) are selected or engineered to model a specific genetic biomarker as it occurs in a patient biopsy. Reference materials (RM) are used for a calibration of the measuring system, for assessment of a measurement procedure, for assigning values to materials, or for quality control.

Molecular reference materials
Molecular reference standards are available in a variety of formats, each of which has strengths and weaknesses. These materials range from synthetic DNA oligonucleotides or patient-derived genomic DNA, to actual patient tissue biopsies with known mutation status.

Proficiency schemes
Proficiency schemes involve the distribution of blinded reference materials to subscription laboratories, and the subsequent scoring and assessment of the proficiency of those labs in their molecular diagnostic testing.

Proficiency schemes are usually organized by not-for-profit organizations, usually government affiliated, to which hundreds of laboratories may subscribe. These schemes are funded with the subscription fees paid by each member laboratory.

Proficiency schemes have historically relied upon patient biopsies with known mutation status for distribution to member laboratories. However, due to the significant rise in the number of labs performing molecular testing (in turn caused by the increase in the number of available targeted drugs whose prescription is linked to the presence or absence of a particular biomarker), patient samples are becoming an unsustainable source of reference material. Increasingly, proficiency scheme organizers are turning to genetically modified cell lines as a sustainable and well defined source of reference material.

Some of the largest proficiency scheme organizers in the world include:
 * College of American Pathologists (CAP) – USA
 * European Molecular Quality Network (EMQN) – UK, Europe, EMEA
 * United Kingdom National External Quality Assessment Scheme (NEQAS) – UK, Europe, EMEA