Integrated proteogenomic characterization of medullary thyroid carcinoma

Author:

Shi Xiao,Sun YaotingORCID,Shen Cenkai,Zhang Yan,Shi Rongliang,Zhang Fan,Liao Tian,Lv Guojun,Zhu Zhengcai,Jiao Lianghe,Li Peng,Xu Tiansheng,Qu Ning,Huang Naisi,Hu Jiaqian,Zhang Tingting,Gu Yanzi,Qin Guangqi,Guan Haixia,Pu Weilin,Li Yuan,Geng Xiang,Zhang Yan,Chen Tongzhen,Huang Shenglin,Zhang Zhikang,Ge Shuting,Wang Wu,Xu Weibo,Yu Pengcheng,Lu Zhongwu,Wang Yulong,Guo Liang,Wang Yu,Guo TiannanORCID,Ji Qinghai,Wei Wenjun

Abstract

AbstractMedullary thyroid carcinoma (MTC) is a rare neuroendocrine malignancy derived from parafollicular cells (C cells) of the thyroid. Here we presented a comprehensive multi-omics landscape of 102 MTCs through whole-exome sequencing, RNA sequencing, DNA methylation array, proteomic and phosphoproteomic profiling. Integrated analyses identified BRAF and NF1 as novel driver genes in addition to the well-characterized RET and RAS proto-oncogenes. Proteome-based stratification of MTCs revealed three molecularly heterogeneous subtypes named as: (1) Metabolic, (2) Basal and (3) Mesenchymal, which are distinct in genetic drivers, epigenetic modification profiles, clinicopathologic factors and clinical outcomes. Furthermore, we explored putative therapeutic targets of each proteomic subtype, and found that two tenascin family members TNC/TNXB might serve as potential prognostic biomarkers for MTC. Collectively, our study expands the knowledge of MTC biology and therapeutic vulnerabilities, which may serve as an important resource for future investigation on this malignancy.

Funder

Natural Science Foundation of Shanghai

National Natural Science Foundation of China

National Key R&D Program of China

Publisher

Springer Science and Business Media LLC

Subject

Cell Biology,Genetics,Molecular Biology,Biochemistry

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