title: RET mutation p.S891A in a Chinese family with familial medullary thyroid carcinoma and associated cutaneous amyloidosis binding OSMR variant p.G513D.
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.
authors.affiliation: Department of Oncologic and Urology Surgery, the 117th PLA Hospital, Wenzhou Medical University, Hangzhou 310004, Zhejiang Province, China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Qi
authors.affiliation: Department of Head and Neck Surgery, Zhejiang Cancer Hospital, Hangzhou 310022, Zhejiang Province, China.
authors.forename: Jian-Qiang
authors.initials: JQ
authors.lastname: Zhao
authors.affiliation: Department of Oncologic and Urology Surgery, the 117th PLA Hospital, Wenzhou Medical University, Hangzhou 310004, Zhejiang Province, China.
authors.forename: Zhen-Guang
authors.initials: ZG
authors.lastname: Chen
authors.affiliation: Department of Oncologic and Urology Surgery, the 117th PLA Hospital, Wenzhou Medical University, Hangzhou 310004, Zhejiang Province, China.
authors.forename: Jin-Lin
authors.initials: JL
authors.lastname: Cao
authors.affiliation: Zhejiang Academy of Medical Sciences, Hangzhou 310007, Zhejiang Province, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Oncologic and Urology Surgery, the 117th PLA Hospital, Wenzhou Medical University, Hangzhou 310004, Zhejiang Province, China.
authors.forename: Nai-Fang
authors.initials: NF
authors.lastname: Liu
authors.affiliation: Department of Oncologic and Urology Surgery, the 117th PLA Hospital, Wenzhou Medical University, Hangzhou 310004, Zhejiang Province, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Oncologic and Urology Surgery, the 117th PLA Hospital, Wenzhou Medical University, Hangzhou 310004, Zhejiang Province, China.
authors.forename: Mao
authors.initials: M
authors.lastname: Sheng
authors.affiliation: Department of Oncologic and Urology Surgery, the 117th PLA Hospital, Wenzhou Medical University, Hangzhou 310004, Zhejiang Province, China.
authors.forename: Er
authors.initials: E
authors.lastname: Fu
authors.affiliation: Department of Oncologic and Urology Surgery, the 117th PLA Hospital, Wenzhou Medical University, Hangzhou 310004, Zhejiang Province, China.|Department of Dermatology, the 117th PLA Hospital, Wenzhou Medical University, Hangzhou 310004, Zhejiang Province, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Guo
authors.affiliation: Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, Jiangsu Province, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Jia
authors.affiliation: Department of Oncologic and Urology Surgery, the 117th PLA Hospital, Wenzhou Medical University, Hangzhou 310004, Zhejiang Province, China.
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Zhang
authors.affiliation: Department of Oncologic and Urology Surgery, the 117th PLA Hospital, Wenzhou Medical University, Hangzhou 310004, Zhejiang Province, China.
authors.forename: Ju-Ming
authors.initials: JM
authors.lastname: Ma
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D028226:Amyloidosis, Familial / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D002116:Calcitonin / Q000378:metabolism; D018276:Carcinoma, Medullary / Q000151:congenital* / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D002648:Child; D002681:China; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D056726:Genetic Association Studies; D014644:Genetic Variation; D005822:Genetic Vectors; D018095:Germ-Line Mutation; D057809:HEK293 Cells; D006579:Heterozygote; D006801:Humans; D008297:Male; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D053681:Oncostatin M Receptor beta Subunit / Q000235:genetics*; D010641:Phenotype; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D012873:Skin Diseases, Genetic / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism
chemical_list: C508348:OSMR protein, human; D053681:Oncostatin M Receptor beta Subunit; D002116:Calcitonin; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human
keywords: OSMR variant; RET mutation; cutaneous amyloidosis; medullary thyroid carcinoma; thyroid neoplasia