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

// Xiao-Ping Qi 1 , Jian-Qiang Zhao 2 , Zhen-Guang Chen 1 , Jin-Lin Cao 1 , Juan Du 3 , Nai-Fang Liu 1 , Feng Li 1 , Mao Sheng 1 , Er Fu 1 , Jian Guo 1, 5 , Hong Jia 4 Yi-Ming Zhang 1 , Ju-Ming Ma 1 1 Department of Oncologic and Urology Surgery, the 117th PLA Hospital, Wenzhou Medical University, Hangzhou 310004, Zhejiang Province, China 2 Department of Head and Neck Surgery, Zhejiang Cancer Hospital, Hangzhou 310022, Zhejiang Province, China 3 Zhejiang Academy of Medical Sciences, Hangzhou 310007, Zhejiang Province, China 4 Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, Jiangsu Province, China 5 Department of Dermatology, the 117th PLA Hospital, Wenzhou Medical University, Hangzhou 310004, Zhejiang Province, China Correspondence to: Xiao-Ping Qi, e-mail: qxplmd@vip.sina.com Keywords: thyroid neoplasia, medullary thyroid carcinoma, cutaneous amyloidosis, RET mutation, OSMR variant Received: March 05, 2015      Accepted: August 14, 2015      Published: August 22, 2015 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.