Abstract
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 language | English |
|---|---|
| Pages (from-to) | 8095-8104 |
| Number of pages | 10 |
| Journal | Oncotarget |
| Volume | 8 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2017 |
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Keywords
- AKT/mTOR
- ATRX
- Cervical small cell neuroendocrine tumor
- ERBB4
- Whole exome sequencing
ASJC Scopus subject areas
- Oncology
Cite this
Cervical small cell neuroendocrine tumor mutation profiles via whole exome sequencing. / Cho, Soo Young; Choi, Minhye; Ban, Hyo Jeong; Lee, Chang Hyeon; Park, Soojun; Kim, Han Kyeom; Kim, Young Sik; Lee, Young Seek; Lee, Ji-Yun.
In: Oncotarget, Vol. 8, No. 5, 2017, p. 8095-8104.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cervical small cell neuroendocrine tumor mutation profiles via whole exome sequencing
AU - Cho, Soo Young
AU - Choi, Minhye
AU - Ban, Hyo Jeong
AU - Lee, Chang Hyeon
AU - Park, Soojun
AU - Kim, Han Kyeom
AU - Kim, Young Sik
AU - Lee, Young Seek
AU - Lee, Ji-Yun
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - AKT/mTOR
KW - ATRX
KW - Cervical small cell neuroendocrine tumor
KW - ERBB4
KW - Whole exome sequencing
UR - http://www.scopus.com/inward/record.url?scp=85018911358&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85018911358&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.14098
DO - 10.18632/oncotarget.14098
M3 - Article
AN - SCOPUS:85018911358
VL - 8
SP - 8095
EP - 8104
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 5
ER -