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High prevalence of RAS mutations in RET-negative sporadic medullary thyroid carcinomas

Margarida M Moura1, Branca M Cavaco, António E Pinto

  • 1Centro de Investigação de Patobiologia Molecular, Instituto Português de Oncologia de Lisboa Francisco Gentil E.P.E., Rua Prof. Lima Basto, 1099-023 Lisboa, Portugal. mmoura@ipolisboa.min-saude.pt

The Journal of Clinical Endocrinology and Metabolism
|February 18, 2011
PubMed
Abstract

Insights

RAS gene mutations are common in RET-negative medullary thyroid carcinoma (MTC), suggesting alternative pathways in MTC development. These findings highlight RAS as a potential therapeutic target in specific MTC subtypes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Sporadic medullary thyroid carcinomas (MTC) often have RET protooncogene mutations.
  • Previous studies identified RET-positive and RET-negative cases in MTC.

Purpose of the Study:

  • Investigate RAS and BRAF protooncogene involvement in RET-negative sporadic MTC.
  • Determine the role of these genes in MTC tumorigenesis.

Main Methods:

  • Analyzed H-, K-, and N-RAS (codons 12, 13, 61) and BRAF (codon 600, exon 11) mutations via PCR and sequencing.
  • Studied 65 sporadic MTC samples (40 RET-positive, 25 RET-negative).

Main Results:

  • RAS mutations found in 56.0% (H-RAS) and 12.0% (K-RAS) of RET-negative MTC.
  • Only 2.5% of RET-positive MTC had a RAS mutation (H-RAS).
  • No N-RAS or BRAF mutations were detected in any samples.

Conclusions:

  • RAS mutations occurred in 68.0% of RET-negative MTC versus 2.5% of RET-positive MTC.
  • RAS and RET protooncogene activation are alternative genetic events in sporadic MTC.
  • RAS mutations are significantly more prevalent in RET-negative MTC.

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