Biomaterial Database

Whole exome sequencing of thymic neuroendocrine tumor with ectopic ACTH syndrome. 2017

Yanli Li, and Ying Peng, and Xiuli Jiang, and Yulong Cheng, and Weiwei Zhou, and Tingwei Su, and Jing Xie, and Xu Zhong, and Dalong Song, and Luming Wu, and Liwen Fan, and Min Li, and Jie Hong, and Weiqing Wang, and Guang Ning, and Yanan Cao

Shanghai Clinical Center for Endocrine and Metabolic DiseasesShanghai Key Laboratory for Endocrine Tumors.

OBJECTIVE Thymic neuroendocrine tumor is the second-most prevalent cause of ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS), which is a rare disease characterized by ectopic ACTH oversecretion from nonpituitary tumors. However, the genetic abnormalities of thymic neuroendocrine tumors with EAS remain largely unknown. We aim to elucidate the genetic abnormalities and identify the somatic mutations of potential tumor-related genes of thymic neuroendocrine tumors with EAS by whole exome sequencing. METHODS Nine patients with thymic neuroendocrine tumors with EAS who were diagnosed at Shanghai Clinical Center for Endocrine and Metabolic Diseases in Ruijin Hospital between 2002 and 2014 were enrolled. We performed whole exome sequencing on the DNA obtained from thymic neuroendocrine tumors and matched peripheral blood using the Hiseq2000 platform. RESULTS We identified a total of 137 somatic mutations (median of 15.2 per tumor; range, 1-24) with 129 single-nucleotide mutations (SNVs). The predominant substitution in these mutations was C:G > T:A transition. Approximately 80% of detected mutations resulted in amino acid changes. However, we failed to discover any recurrent mutations in these nine patients. By functional predictions, HRAS, PAK1 and MEN1, previously reported in neuroendocrine tumors, were identified as candidate tumor-related genes associated with thymic neuroendocrine tumors. CONCLUSIONS Using whole exome sequencing, we identified genetic abnormalities in thymic neuroendocrine tumors with EAS. Thereby, this study acts as a further supplement of the genetic features of neuroendocrine tumors. Somatic mutations of three potential tumor-related genes (HRAS, PAK1 and MEN1) might contribute to the tumorigenesis of thymic neuroendocrine tumors with EAS.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000182	ACTH Syndrome, Ectopic	Symptom complex due to ACTH production by non-pituitary neoplasms.	Ectopic ACTH Syndrome,ACTH Syndromes, Ectopic,Ectopic ACTH Syndromes,Syndrome, Ectopic ACTH,Syndromes, Ectopic ACTH
D000324	Adrenocorticotropic Hormone	An anterior pituitary hormone that stimulates the ADRENAL CORTEX and its production of CORTICOSTEROIDS. ACTH is a 39-amino acid polypeptide of which the N-terminal 24-amino acid segment is identical in all species and contains the adrenocorticotrophic activity. Upon further tissue-specific processing, ACTH can yield ALPHA-MSH and corticotrophin-like intermediate lobe peptide (CLIP).	ACTH,Adrenocorticotropin,Corticotropin,1-39 ACTH,ACTH (1-39),Adrenocorticotrophic Hormone,Corticotrophin,Corticotrophin (1-39),Corticotropin (1-39),Hormone, Adrenocorticotrophic,Hormone, Adrenocorticotropic
D000328	Adult	A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available.	Adults
D013953	Thymus Neoplasms	Tumors or cancer of the THYMUS GLAND.	Cancer of Thymus,Thymus Cancer,Thymus Tumors,Cancer of the Thymus,Neoplasms, Thymic,Neoplasms, Thymus,Thymic Cancer,Thymic Neoplasms,Thymic Tumors,Cancer, Thymic,Cancer, Thymus,Cancers, Thymic,Cancers, Thymus,Neoplasm, Thymic,Neoplasm, Thymus,Thymic Cancers,Thymic Neoplasm,Thymic Tumor,Thymus Cancers,Thymus Neoplasm,Thymus Tumor,Tumor, Thymic,Tumor, Thymus,Tumors, Thymic,Tumors, Thymus
D016283	Proto-Oncogene Proteins p21(ras)	Cellular proteins encoded by the H-ras, K-ras and N-ras genes. The proteins have GTPase activity and are involved in signal transduction as monomeric GTP-binding proteins. Elevated levels of p21 c-ras have been associated with neoplasia. This enzyme was formerly listed as EC 3.6.1.47.	Proto-Oncogene Proteins c-ras,c-Ha-ras p21,c-Ki-ras p21,p21(N-ras),p21(c-Ha-ras),p21(c-Ki-ras),p21(c-ras),p21(ras),ras Proto-Oncogene Protein p21,Proto-Oncogene Protein p21(c-Ha-ras),Proto-Oncogene Protein p21(c-Ki-ras),Proto-Oncogene Protein p21(c-N-ras),Proto-Oncogene Protein p21(ras),Proto-Oncogene Protein ras,c-ras Proteins,p21 c-H-ras,p21 c-Ha-ras,p21 c-K-ras,p21 c-Ki-ras,p21 c-ras,ras Proto-Oncogene Product p21,Proteins c-ras, Proto-Oncogene,Proto Oncogene Protein ras,Proto Oncogene Proteins c ras,c Ha ras p21,c Ki ras p21,c ras Proteins,c-H-ras, p21,c-Ha-ras, p21,c-K-ras, p21,c-Ki-ras, p21,c-ras, Proto-Oncogene Proteins,c-ras, p21,p21 c H ras,p21 c Ha ras,p21 c K ras,p21 c Ki ras,p21 c ras,p21, c-Ha-ras,p21, c-Ki-ras,ras Proto Oncogene Product p21,ras Proto Oncogene Protein p21,ras, Proto-Oncogene Protein
D054462	p21-Activated Kinases	A family of serine-threonine kinases that bind to and are activated by MONOMERIC GTP-BINDING PROTEINS such as RAC GTP-BINDING PROTEINS and CDC42 GTP-BINDING PROTEIN. They are intracellular signaling kinases that play a role the regulation of cytoskeletal organization.	PAK Kinase,p21-Activated Kinase,Oligophrenin-3,PAK Kinases,PAK-1 Kinase,PAK-2 Kinase,PAK1 Kinase,PAK2 Kinase,PAK3 Kinase,PAK65,Serine-Threonine-Protein Kinase PAK 1,Serine-Threonine-Protein Kinase PAK 3,alpha p21-Activated Kinase,alpha-PAK,beta p21-Activated Kinase,beta-PAK,gamma-PAK,p21-Activated Kinase 1,p21-Activated Kinase 2,p21-Activated Kinase 3,p65(PAK),p65PAK Protein,Kinase, PAK,Kinase, p21-Activated,Kinases, PAK,Kinases, p21-Activated,Oligophrenin 3,PAK 1 Kinase,PAK 2 Kinase,Serine Threonine Protein Kinase PAK 1,Serine Threonine Protein Kinase PAK 3,alpha p21 Activated Kinase,beta p21 Activated Kinase,gamma PAK,p21 Activated Kinase,p21 Activated Kinase 1,p21 Activated Kinase 2,p21 Activated Kinase 3,p21 Activated Kinases,p21-Activated Kinase, beta