Cervical small cell neuroendocrine tumor mutation profiles via whole exome sequencing

Soo Young Cho, Minhye Choi, Hyo Jeong Ban, Chang Hyeon Lee, Soojun Park, Han Kyeom Kim, Young Sik Kim, Young Seek Lee, Ji Yun Lee

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)


Cervical small cell neuroendocrine tumors (CSCNETs) are rare, aggressive neuroendocrine tumors (NETs). Reliable diagnostic and prognostic CSCNET markers are lacking, making diagnosis and prognosis prediction difficult, and treatment strategies limited. Here we provide mutation profiles for five tumor-normal paired CSCNETs using whole exome sequencing (WES). We expanded our assessment of frequently mutated genes to include publicly available data from 55 small intestine neuroendocrine tumors, 10 pancreatic neuroendocrine tumors, 42 small cell lung cancers, six NET cell lines, and 188 cervical cancers, along with our five CSCNETs. We identified 1,968 somatic mutations, including 1,710 missense, 106 nonsense, 144 splice site, 4 lncRNA, 3 nonstop, and 1 start codon mutation. We assigned functions to the 114 most frequently mutated genes based on gene ontology. ATRX, ERBB4, and genes in the Akt/mTOR pathway were most frequently mutated. Positive cytoplasmic ERBB4 immunohistochemical staining was detected in all CSCNET tumors tested, but not in adjacent normal tissues. To our knowledge, this study is the first to utilize WES in matched CSCNET and normal tissues to identify somatic mutations. Further studies will improve our understanding of how ATRX and ERBB4 mutations and AKT/mTOR signaling promote CSCNET tumorigenesis, and may be leveraged in novel anti-cancer treatment strategies.

Original languageEnglish
Pages (from-to)8095-8104
Number of pages10
Issue number5
Publication statusPublished - 2017

Bibliographical note

Funding Information:
This research was supported by the Collaborative Genome Program for Fostering New Post-Genome Industry through the National Research Foundation of Korea (NRF), which is funded by the Ministry of Science ICT and Future Planning (NRF-2014M3C9A3064693), by the Basic Science Research Program Grant (NRF-2014R1A2A2A01003566) from the National Research Foundation of Korea (NRF), which is funded by the Ministry of Education, Science and Technology (MEST), Republic of Korea, and Republic of Korea, and Future Planning and Bio-Synergy Research Project (NRF-2014M3A9C4066487) of the Ministry of Science, ICT and Future Planning through the National Research Foundation.


  • AKT/mTOR
  • ATRX
  • Cervical small cell neuroendocrine tumor
  • ERBB4
  • Whole exome sequencing

ASJC Scopus subject areas

  • Oncology


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