Novel tandem germline RET proto-oncogene mutations in a patient with multiple endocrine neoplasia type 2B: report of a case and a literature review of tandem RET mutations with in silico analysis

Head Neck. 2013 Dec;35(12):E363-8. doi: 10.1002/hed.23241. Epub 2013 Mar 6.

Abstract

Background: Multiple endocrine neoplasia type 2B (MEN2B) is the rarest and most aggressive form of MEN2. MEN2B cases usually carry either an M918T or A883T mutation of the RET, but to date, there are 3 atypical MEN2B caused by tandem mutations.

Methods and results: A 32-year-old woman with no family history of medullary thyroid carcinoma (MTC) presented with a neck tumor and multiple mucosal nodules. She was diagnosed with MEN2B. Genetic analyses of RET revealed that she had 2 mutations, Q781R and V804M. Subclone and genetic analyses revealed that Q781R was on the paternal allele and V804M was a de novo. In silico analysis of the tandem mutations showed a high prediction score.

Conclusions: We describe a novel combination of tandem RET mutations (Q781R/V804M) in a MEN2B-like patient. In silico analysis showed a high prediction score, which was compatible with the clinical phenotype in the present case.

Keywords: MEN2B; RET; de novo; in silico; tandem mutation.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Amino Acid Substitution
  • Calcitonin / blood
  • Computer Simulation
  • Female
  • Genotype
  • Germ-Line Mutation*
  • Humans
  • Lymphatic Metastasis
  • Mouth Mucosa / pathology
  • Multiple Endocrine Neoplasia Type 2b / genetics*
  • Multiple Endocrine Neoplasia Type 2b / pathology
  • Multiple Endocrine Neoplasia Type 2b / surgery
  • Neck Dissection
  • Pedigree
  • Polymerase Chain Reaction
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-ret / genetics*
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / pathology
  • Thyroid Neoplasms / surgery
  • Thyroidectomy

Substances

  • MAS1 protein, human
  • Proto-Oncogene Mas
  • Calcitonin
  • Proto-Oncogene Proteins c-ret
  • RET protein, human