RET mutation p.S891A in a Chinese family with familial medullary thyroid carcinoma and associated cutaneous amyloidosis binding OSMR variant p.G513D.
Oncotarget
; 6(32): 33993-4003, 2015 Oct 20.
Article
de En
| MEDLINE
| ID: mdl-26356818
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.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Maladies génétiques de la peau
/
Tumeurs de la thyroïde
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Carcinome médullaire
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Néoplasie endocrinienne multiple de type 2a
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Amyloïdose familiale
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Protéines proto-oncogènes c-ret
/
Récepteur bêta à l'oncostatine M
/
Mutation
Type d'étude:
Risk_factors_studies
Limites:
Adolescent
/
Adult
/
Aged
/
Child
/
Female
/
Humans
/
Male
Pays/Région comme sujet:
Asia
Langue:
En
Journal:
Oncotarget
Année:
2015
Type de document:
Article
Pays d'affiliation:
Chine