Identification of a secondary RET mutation in a pediatric patient with relapsed acute myeloid leukemia leads to the diagnosis and treatment of asymptomatic metastatic medullary thyroid cancer in a parent: a case for sequencing the germline

Cold Spring Harb Mol Case Stud. 2019 Apr 1;5(2):a003889. doi: 10.1101/mcs.a003889. Print 2019 Apr.

Abstract

The incorporation of tumor-normal genomic testing into oncology can identify somatic mutations that inform therapeutic measures but also germline variants associated with unsuspected cancer predisposition. We describe a case in which a RET variant was identified in a 3-yr-old male with relapsed leukemia. Sanger sequencing revealed the patient's father and three siblings carried the same variant, associated with multiple endocrine neoplasia 2A (MEN2A). Evaluation of the father led to the diagnosis and treatment of metastatic medullary thyroid carcinoma. Detection of RET mutations in families with hereditary MTC allows for genetic risk stratification and disease surveillance to reduce morbidity and mortality.

Keywords: acute myeloid leukemia; medullary thyroid carcinoma.

Publication types

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

MeSH terms

  • Carcinoma, Neuroendocrine / diagnosis*
  • Carcinoma, Neuroendocrine / genetics
  • Child, Preschool
  • Fathers
  • Germ-Line Mutation*
  • Humans
  • Incidental Findings
  • Leukemia, Myeloid, Acute / genetics*
  • Male
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local / genetics*
  • Pedigree
  • Proto-Oncogene Proteins c-ret / genetics*
  • Sequence Analysis, DNA
  • Thyroid Neoplasms / diagnosis*
  • Thyroid Neoplasms / genetics

Substances

  • Proto-Oncogene Proteins c-ret
  • RET protein, human

Supplementary concepts

  • Thyroid cancer, medullary