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Related Concept Videos

The Ras Gene02:38

The Ras Gene

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The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
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Discriminating Interpatient Variabilities of RAS Gene Variants for Precision Detection of Thyroid Cancer.

Guodong Fu1, Ronald S Chazen1, Christina MacMillan1,2

  • 1Alex and Simona Shnaider Research Laboratory in Molecular Oncology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Sinai Health, Toronto, Ontario, Canada.

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Interpatient differences in RAS variants within thyroid tumors were identified, showing association with lower recurrence risk. Combining RAS, BRAF, and TERT variant analysis improves malignancy detection in thyroid nodules.

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Area of Science:

  • Genomic analysis of thyroid neoplasms
  • Molecular diagnostics in oncology
  • Cancer genomics and personalized medicine

Background:

  • Interpatient variability in genomic variants can indicate differing tumor statuses.
  • Understanding these variations is crucial for accurate thyroid nodule diagnosis.

Purpose of the Study:

  • To delineate interpatient variabilities in RAS variants in thyroid tumors according to the WHO classification.
  • To assess the diagnostic significance of these variants in cancer detection.

Main Methods:

  • Prospective diagnostic study analyzing surgically resected thyroid tumors and FNA biopsies.
  • Quantitative detection of RAS (NRAS, HRAS, KRAS), BRAF V600E, and TERT promoter variants using digital PCR.
  • Analysis of variant allele fractions (VAFs) and comparison with histopathologic diagnoses.

Main Results:

  • RAS variants were found in 20.3% of thyroid tumors, with varying VAFs.
  • RAS variant distribution differed significantly between NIFTPs and invasive follicular variant papillary thyroid carcinomas.
  • Inclusion of RAS variants improved sensitivity for malignancy detection when combined with BRAF and TERT assays.

Conclusions:

  • Interpatient differences in RAS variants, along with BRAF and TERT variants, can aid in preoperative precision diagnosis of thyroid nodules.
  • Discriminating these variabilities may enhance diagnostic accuracy in indeterminate and nondiagnostic fine-needle aspirates.