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TCGA'S Study of Papillary Thyroid Carcinoma

What is thyroid cancer?

Thyroid cancer develops in the follicular cells of the thyroid. The thyroid gland is located at the front of the neck below the voice box. The thyroid gland secretes hormones that control heart rate, blood pressure, body temperature and weight. It is estimated that approximately 45,000 Americans were diagnosed and about 1,700 died from thyroid cancer in 2010.1 Papillary thyroid carcinoma, the type being studied by TCGA, accounts for 80% of all thyroid cancer cases. It is diagnosed most commonly in patients who are around the age of 49 and it is more common in women.1 Thyroid cancer grows very slowly and if it is diagnosed early, this cancer can be cured. Additional information about thyroid cancer.

What have TCGA researchers learned about thyroid cancer?

  • A few different groups of molecular alterations drive papillary thyroid carcinoma:
    • The majority of papillary thyroid carcinomas studied were driven by mutations in either BRAF (specifically, BRAF-V600E) or RAS, both of which deregulate the mitogen-activated protein kinase (MAPK) signaling pathway
    • Novel driver gene EIF1AX impairs the MAPK pathway and is mutually exclusive from BRAF and RAS mutations
    • Oncogenic drivers were identified in 96.5% of tumor samples
  • Classification of papillary thyroid carcinomas may potentially be refined to include a tumor’s likeness to BRAF-V600E driven tumors versus RAS driven tumors
    • BRAFV-600E driven tumors and RAS driven tumors showed distinct molecular profiles that differentially affect downstream signaling: BRAF-V600E driven tumors demonstrate high MAPK-signaling while RAS driven tumors demonstrate lower MAPK-signaling
    • A thyroid differentiation scoring system helps determine whether tumors are BRAF-V600E driven or RAS driven
    • Heterogeneous gene expression for the BRAF-V600E subtype suggests further stratification of the subtype could lead to better prognostic value
  • Potential therapeutic avenues based on molecular features may be pursued:
    • BRAF-V600E and RAS driven tumors may respond differently to treatments such as radioactive iodine and targeted therapy

TCGA's study of papillary thyroid carcinoma

TCGA Research Network publications

Find NCI-supported thyroid cancer clinical trials

Selected References

1American Cancer Society. Cancer Facts and Figures 2010. Atlanta: American Cancer Society, Inc. 2010.

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