How does Foundation Medicine Comprehensive Genomic Profiling work?

Foundation Medicine looks broadly across the genome.1,3

Foundation Medicine is a Comprehensive Genomic Profiling (CGP) approach that interrogates the entire coding region of relevant cancer genes and selected introns to:1,3

  • Accurately detect all four classes of genomic alterations1,3
  • Identify TMB and MSI with no additional tests, in a single report4,5,10
             
             
a   b c d e f

No filter results

    315 genes interrogated
     
    Insertions & deletions
    Base substitutions
    Copy number alterations
    Rearrangements
  28 select introns profiled

No filter results

MSI: microsatellite instability; TMB: tumour mutation burden.

Foundation Medicine detects genomic alterations with high sensitivity and specificity.2,8,9

As Foundation Medicine CGP is a next-generation sequencing approach that uses hybrid capture-based target enrichment it can accurately detect genomic alterations, as well as TMB and MSI status, with higher sensitivity and specificity compared to PCR-based target enrichment.2-4,8-10

Foundation Medicine FAQs

  • How is Comprehensive Genomic Profiling (CGP) different to standard diagnostic techniques, such as FISH, IHC and RT-PCR?

    Standard diagnostic techniques, such as FISH, IHC and RT-PCR, are specific – the genomic target and class of alteration needs to be pre-determined, which means some alterations can be missed.44-47

     

    In addition, as standard diagnostic techniques can only detect one or two classes of genomic alterations, they are limited in their ability to detect all possible alterations.2

     

    What’s more, sequential biomarker testing results in high tissue depletion, which can preclude subsequent tests that may be needed for rare markers.14

     

    In contrast, the Foundation Medicine CGP approach identifies all four major classes of genomic alterations, including base substitutions, insertions and deletions, copy number alterations, and rearrangements, in a single tissue-sparing assay.1,3,14

     

    FISH: fluorescence in situ hybridisation; IHC: immunohistochemistry; RT-PCR: real-time or reverse transcriptase polymerase chain reaction.

     

  • How does the type of NGS technology used determine how well genomic alterations are detected?

    PCR-based NGS hotspot analysis employs a selective approach to analyse the gene sequence.48 The use of primers with pre-determined start and stop locations means that reads are stacked in vertical columns at the same region of the gene, missing alterations in other regions.48

     

    Foundation Medicine hybrid capture-based NGS employs a tiled approach to recreate the entire gene sequence.48 The use of overlapping probes means reads are stacked in a staggered or step-wise manner, which creates continuous alignment that ensures no alterations are missed.48

     

    NGS: next-generation sequencing

  • How well does Comprehensive Genomic Profiling (CGP) detect alterations compared to PCR-based NGS hotspot testing?

    PCR-based NGS hotspot analysis only sequences selected regions of a gene, leaving many gene alterations missed.14 In contrast, Foundation Medicine CGP uses hybrid capture-based target enrichment to look broadly across the genome, interrogating the entire coding region of relevant cancer genes and selected introns.1,3

     

    This means that Foundation Medicine can detect all four classes of genomic alterations, as well as TMB and MSI, with higher sensitivity and specificity.2-4,10

     

    MSI: microsatellite instability; TMB: tumour mutation burden

  • How can Foundation Medicine CGP help physicians navigate the clinical complexities of cancer care?

    Cancer care is becoming increasingly complex due to the increasing number of potential genomic targets being identified and the increasing availability of targeted therapies.14, 49-51

     

    Because standard diagnostic techniques (e.g. FISH, IHC, RT-PCR) only test for a handful of possibilities, there are potentially many other classes of alterations, and treatment possibilities, that can be missed.2,52 As a clinically validated pan-cancer CGP approach, Foundation Medicine enables accurate detection of all four classes of genomic alterations,2,5-9 in a single tissue-sparing assay.

     

    All FoundationOne® samples are simultaneously profiled for TMB and MSI status, while FoundationOne®Heme samples are simultaneously profiled for TMB status.4,5,7,10

     

    By providing physicians with detailed insight into their patient’s cancer, Foundation Medicine can open up more treatment possibilities for patients.1-4

     

    FISH: fluorescence in situ hybridisation; IHC: immunohistochemistry; RT-PCR: real-time or reverse transcriptase polymerase chain reaction; MSI: microsatellite instability; TMB: tumour mutation burden

  • Why is Comprehensive Genomic Profiling so important?

    The significant number of genomic alterations not routinely tested for, or not detected by standard techniques, leaves many actionable alterations unidentified.52,53 For example, in a study of ~7,300 tumours from 27 distinct tissue types tested, it was found that the majority of HER2/ERBB2 alterations were missed by FISH and IHC.52

     

    Missing actionable alterations can impact treatment possibilities for patients.52,53 Comprehensive Genomic Profiling can help find the genomic alterations that other tests miss, so that new treatment possibilities may become possible for many patients.1-3

     

    FISH: fluorescence in situ hybridisation; IHC: immunohistochemistry.

  • Do all FOUNDATION MEDICINE results lead to actionable treatment options?

    While clinical trials have demonstrated that Foundation Medicine can detect more actionable alterations compared to standard diagnostic techniques and NGS hotspot testing, not all profiling results lead to actionable treatment options.1,2,8,14,15 

     

    However, even if no actionable alterations are detected, the result can still be of value in clinical practice, by helping to rule out uncertainties and determine an alternative course of action.

     

    NGS: next-generation sequencing

  • Does Foundation Medicine profiling predict response to chemotherapy or the likelihood of recurrence?

    These profiles are not designed to predict response to chemotherapy or recurrence of disease. They help to match the genomic alterations present in a cancer with specific targeted and immunotherapies either approved, launched or being investigated in clinical trials.