Consider testing all patients immediately upon diagnosis with mCRC to get a full clinical picture including BRAF status. There are a number of testing methodologies that are currently available, depending on the sample type and other considerations.
ctDNA in liquid-based NGS
Circulating tumor DNA, or ctDNA, is fragmented DNA released by dying tumor cells into the bloodstream and can be collected in a blood sample.1
Sample type: liquid based
Potential advantages:
- Less invasive than tissue-based testing2
- Able to capture tumor heterogeneity2
- Can be collected and analyzed repeatedly for monitoring tumor response and/or relapse2
- Faster turnaround time than tissue-based testing2
- High concordance rate with tissue-based testing
- In a retrospective, large-scale genomic profiling study of patients with mCRC and without prior chemotherapy, the BRAF mutation had a ~97% concordance rate between tissue and liquid biopsy3,4*
Potential limitations:
- May require tumor biopsy results for confirmation or detection of false negatives5
- May miss genetic alterations in early disease states with low ctDNA shedding6
Turnaround time: 7-10 days7
PCR
Polymerase chain reaction, or PCR, is a laboratory technique that selectively amplifies a specific DNA sequence and can detect specific known mutations.8,9
Sample type: liquid or tissue based
Potential advantages:
- High levels of sensitivity (variant allele frequency [VAF] for detection of ≤0.01%)9
Potential limitations:
- Limited to detecting either a single or a small number of known mutations9
Turnaround time: 1-3 days10†
IHC
Immunohistochemistry, or IHC, testing uses antibodies to identify the presence of specific protein markers, such as a mutated BRAF protein, in a tissue sample.11
Sample type: tissue based
Potential advantages:
- High sensitivity and specificity12
- Potential for faster turnaround time than other test types12
- Widely available and globally established11
Potential limitations:
- More invasive than a blood-based sample2
- May be more difficult to interpret due to staining variability12
- Tumor heterogeneity may interfere with establishing true mutational profile2
Turnaround time: 1 day13‡
Resources and common questions about testing
*Patients in this study were enrolled in GOZILA, a nationwide plasma genomic profiling study involving 31 core cancer institutions in Japan.4
†Defined as the time from the start to the result of the test. Does not include sample preparation, cutting slides, quality control by the pathologist, and reporting of results.10
‡In-lab time.13
NGS, next-generation sequencing.
References
- Tao XY, Li QQ, Zeng Y. Mol Cancer. 2024;23(1):145.
- Lone SN, Nisar S, Masoodi T, et al. Mol Cancer. 2022;21(1):79.
- Aoki Y, Nakamura Y, Denda T, et al. JCO Precis Oncol. 2023;7:e2200688 [Appendix].
- Aoki Y, Nakamura Y, Denda T, et al. JCO Precis Oncol. 2023;7:e2200688.
- Benavides M, Alcaide-Garcia J, Torres E, et al. ESMO Open. 2022;7(3):100481.
- Nikanjam M, Kato S, Kurzrock R. J Hematol Oncol. 2022;15(1):131.
- Malla M, Loree JM, Kasi PM, et al. J Clin Oncol. 2022;40(24):2846-2857.
- National Human Genome Institute. Talking Glossary of Genomic and Genetic Terms: Polymerase Chain Reaction (PCR). NIH, 2024. Accessed December 4, 2024. https://www.genome.gov/genetics-glossary/Polymerase-Chain-Reaction-PCR
- Dasari A, Morris VK, Allegra CJ, et al. Nat Rev Clin Oncol. 2020;17(12):757-770.
- Bisschop C, Ter Elst A, Bosman LJ, et al. Melanoma Res. 2018;28(2):96-104.
- Gamde SM, Francis L, Adisa JO. Perspect Med Res. 2024;12(2):15-21.
- Kwon JH, Jeong BK, Yoon YS, Yu CS, Kim J. J Pathol Transl Med. 2018;52(3):157-163.
- Hummel M, Hegewisch-Becker S, Neumann JHL, et al. Patholege. 2021;42(Suppl1):S98-S109.