Combination Testing
ThyGeNEXT + ThyraMIR is the only testing platform that utilizes both mutational and microRNA markers to aid patient management
Why Combination Testing?
- Not all mutations are strongly predictive of malignancy1
- Strong driver mutations, such as BRAF V600E, TERT promoter, and RET fusions have proven useful in surgical decision-making2-9
- Weak driver mutations, such as RAS or PAX8/PPAR, carry less certainty10,11
- microRNA classification complements cytology and mutation analysis1
Variable PPV of RAS Mutations
- RAS mutations are common in adenomas14
- PPV of RAS mutations can vary due to differences in risk of malignancy among histopathologic subtypes13
- microRNA classification further risk-stratified patients with weak driver mutations, including RAS12
“Mutations strongly associated with malignancy, such as BRAF V600E, RET fusions, and TERT, can assist in surgical decision-making. Other mutations considered weak drivers of cancer, such as RAS, carry less certainty.”12
Patient Management with ThyGeNEXT + ThyraMIR
- Strong driver mutations, such as BRAF V600E, TERT promoter, and RET/PTC help inform consideration of surgical intervention2-9
- microRNA classification assists with variable mutational profiles
- Lack of detectable mutations1
- Weak driver mutations, such as RAS1,12
Markers that MatterTM
Strategically Designed Mutation Panel for the Optimal Management of Thyroid Nodules
| DNA mutation panel | RNA panel (# fusions) | ALK | ALK (2) |
|---|---|
| BRAF | BRAF (3) |
| GNAS | NTRK (8) |
| KRAS | RET (14) |
| NRAS | THADA (5) |
| PIK3CA | mRNA markers: NKX2-1, PAX8, TBP, USP33 |
| PTEN | |
| RET | |
| TERT |
- BRAF V600E, TERT promoter, and ALK mutations can reliably help predict aggressive biological features of thyroid cancer8,14,15
| FTC | PTC | PDTC | ATC | MTC | |
|---|---|---|---|---|---|
| Upregulated | miR-222-3p | miR-222-3p | miR-222-3p | miR-222-3p | miR-375 |
| miR-146b-5p | miR-146b-5p | miR-146b-5p | miR-146b | ||
| miR-31-5p | miR-551b | ||||
| Downregulated | MiR-139-5p | miR-204-5p | miR-204-5p | miR-138-1-3p | |
| miR-155-5p | miR-29b-1-5p | ||||
| miR-155-5p |
- miRNAs can help rule in all types of thyroid cancers16,17
References
1. Banizs AB, Silverman JF. Diagn Cytopathol. 2019;47(4):268-274. 2. Liu T, et al. Oncogene. 2014;33(42):4978-4984. 3. Landa I, et al. J Clin Endocrinol Metab. 2013;98(9):E1562-1566. 4. Nikiforov YE, et al. J Clin Endocrinol Metab. 2011;96(11):3390-3397. 5. Santoro M, Carlomagno F. Cold Spring Harb Perspect Biol. 2013;5(12):a009233. 6. Liu X, et al. Endocr Relat Cancer. 2013;20(4):603-610. 7. Fussey JM, et al. Clin Endocrinol (Oxf). 2019;91(6):697-707. 8. Melo M, et al. J Clin Endocrinol Metab. 2014;99 (5):E754-765. 9. Censi S, et al. Eur J Endocrinol. 2019;181(1):1-11. 10. Marcadis AR, et al. Surgery. 2019;165(1):17-24. 11. Guan H, et al. Thyroid. 2020;30(4):536-547. 12. Lupo MA, et al. Diagn Cytopathol. 2020;1–11. https://doi.org/10.1002/dc.24564 13.Nabhan F, et al. Thyroid. 2018;28(6):729-738. 14. Liu R, et al. Endocr Relat Cancer. 2016;23(3):R143-R155. 15. Bae JS, et al. Diagn Pathol. 2016;11:21. 16.Visone R, Pallante P, Vecchione A, et al. Specific microRNAs are downregulated in human thyroid anaplastic carcinomas. Oncogene. 2007;26(54):7590-7595. 17. Nikiforova, MN, Tseng GC, Steward D, et al. MicroRNA expression profiling of thyroid tumors: biological significance and diagnostic utility. J Clin Endocrinol Metab. 2008;93(5):1600-1608
