The top 7 attributes of cell line-derived reference standards for oncology assays.

Cell line-derived reference standards offer significant advantages over other types of controls used in oncology assays due to their ability to closely mimic the genetic complexity of patient samples.

These controls are developed to represent a spectrum of genetic variations like insertion/deletion polymorphisms (INDELs), single nucleotide variants (SNVs), copy number variations (CNVs) and fusions. The resulting standards facilitate both cancer-specific and comprehensive pan-cancer analyses in cancer research.

When developing our Mimix™ portfolio of ready-made reference standards, our scientists used these seven attributes as their guideposts:

1. Full genomic complexity: Cell line-derived controls encapsulate a range of biologically relevant oncology mutations within their natural genomic context, providing a robust way to test and monitor oncology assays.
2. Reproducible and reusable: Cell line-derived materials provide a stable, reproducible, and reusable source of reliable controls, unlike patient-derived controls that are finite and may not yield similar results when replaced.
3. Stability and storage: Designed for longevity, cell line-derived materials have a shelf life of up to 60 months at standard refrigeration temperatures. This stability is particularly advantageous for liquid biopsy standards, some of which are offered in synthetic plasma and are stable for up to 13 months.
4. Defined allele frequencies: Cell line-derived controls encompass a wide range of allele frequencies, mirroring the genetic diversity found in tumors, ranging from germline to low-frequency somatic mutations. This breadth is critical for establishing the limit of detection (LOD) in new gene panels., a standard practice in NGS assays. Very low allelic frequencies enable the verification of minimal residual disease (MRD) assays.
5. Multiple types of variants: Cell line-derived reference materials are customizable to test a wide array of mutations, including SNVs, CNVs, Indels, and fusions. Given cancer's heterogeneous nature, individuals may possess multiple mutation types, underscoring the need for comprehensive reference material.
6. Versatile formats: To closely emulate patient samples and integrate seamlessly with laboratory workflows, a variety of control formats are available, like FFPE curls/blocks, ctDNA, gDNA, formalin compromised DNA (fcDNA), fcRNA, genome in a bottle. This flexibility allows for tailored assay development and monitoring across different stages of testing procedures.
7. Compatibility across platforms: These reference materials are designed to be used with a variety of genetic testing methods, including qPCR, ddPCR, Sanger sequencing, microarray, and NGS, supporting the evolution of precision oncology testing.

The use of reliable cell line-derived reference materials is crucial for the development of accurate and reliable oncology tests. Industry consortia like the Medical Device Innovation Consortium recognize the significance of reference standards for enhancing the verification and regulatory review processes in cancer research testing.

Revvity’s Mimix portfolio of cell line-derived cancer-specific and pan-cancer reference standards, that facilitate cancer research, includes FFPE ready-made controls:  

• Colorectal cancer FFPE reference standard
• Prostate cancer FFPE reference standard
• PTEN loss FFPE reference standard
• Lymphoid cancer FFPE reference standard

For a deeper dive into the advantages of cell line-derived reference materials in oncology, please download our white paper. 

For research use only. Not for use in diagnostic procedures.