RET mutation p.S891A in a Chinese family with familial medullary thyroid carcinoma and associated cutaneous amyloidosis binding OSMR variant p.G513D

Oncotarget. 2015 Oct 20;6(32):33993-4003. doi: 10.18632/oncotarget.4992.

Abstract

There are no reports on the relationship between familial medullary thyroid carcinoma (FMTC) associated with cutaneous amyloidosis (CA) and RET or OSMR/IL31RA gene mutations. In this study, we investigated a Chinese family with FMTC/CA and found a recurrent RET c.2671T>G (p.S891A) mutation in six of 17 family members. Three of the six p.S891A mutation carriers presented with medullary thyroid carcinoma (MTC). Of them, three (two with and one without MTC) were diagnosed as having combined lichen/macular biphasic CA. We also identified a novel RET variant, c.1573C>T (p.R525W) in five members. Of them, three carriers had no evidence of thyroid/skin or basal serum/stimulated calcitonin abnormalities. In vitro cell proliferation assay indicated that oncogenic activity of RET p.S891A was slightly enhanced by p.R525W, whereas p.R525W alone had no effect on cell proliferation. Meanwhile, we identified a novel OSMR variant, c.1538G>A (p.G513D) in seven members. We noticed that three OSMR p.G513D carriers presenting with CA also had the RET p.S891A mutation. Our investigation indicated that the RET p.S891A mutation combined with OSMR p.G513D may underlie a novel phenotype manifesting as FMTC and CA.

Keywords: OSMR variant; RET mutation; cutaneous amyloidosis; medullary thyroid carcinoma; thyroid neoplasia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Amyloidosis, Familial / complications
  • Amyloidosis, Familial / genetics*
  • Amyloidosis, Familial / metabolism
  • Calcitonin / metabolism
  • Carcinoma, Medullary / congenital*
  • Carcinoma, Medullary / genetics
  • Carcinoma, Medullary / metabolism
  • Cell Proliferation
  • Child
  • China
  • DNA Mutational Analysis
  • Family Health
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Genetic Association Studies
  • Genetic Variation
  • Genetic Vectors
  • Germ-Line Mutation
  • HEK293 Cells
  • Heterozygote
  • Humans
  • Male
  • Multiple Endocrine Neoplasia Type 2a / genetics*
  • Multiple Endocrine Neoplasia Type 2a / metabolism
  • Mutation*
  • Oncostatin M Receptor beta Subunit / genetics*
  • Phenotype
  • Proto-Oncogene Proteins c-ret / genetics*
  • Skin Diseases, Genetic / complications
  • Skin Diseases, Genetic / genetics*
  • Skin Diseases, Genetic / metabolism
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / metabolism

Substances

  • OSMR protein, human
  • Oncostatin M Receptor beta Subunit
  • Calcitonin
  • Proto-Oncogene Proteins c-ret
  • RET protein, human

Supplementary concepts

  • Amyloidosis, Primary Cutaneous
  • Familial medullary thyroid carcinoma