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Identification of a novel RASD1 somatic mutation in a USP8 -mutated corticotroph adenoma.
- Source :
-
Cold Spring Harbor molecular case studies [Cold Spring Harb Mol Case Stud] 2017 May; Vol. 3 (3), pp. a001602. - Publication Year :
- 2017
-
Abstract
- Cushing's disease (CD) is caused by pituitary corticotroph adenomas that secrete excess adrenocorticotropic hormone (ACTH). In these tumors, somatic mutations in the gene USP8 have been identified as recurrent and pathogenic and are the sole known molecular driver for CD. Although other somatic mutations were reported in these studies, their contribution to the pathogenesis of CD remains unexplored. No molecular drivers have been established for a large proportion of CD cases and tumor heterogeneity has not yet been investigated using genomics methods. Also, even in USP8 -mutant tumors, a possibility may exist of additional contributing mutations, following a paradigm from other neoplasm types where multiple somatic alterations contribute to neoplastic transformation. The current study utilizes whole-exome discovery sequencing on the Illumina platform, followed by targeted amplicon-validation sequencing on the Pacific Biosciences platform, to interrogate the somatic mutation landscape in a corticotroph adenoma resected from a CD patient. In this USP8 -mutated tumor, we identified an interesting somatic mutation in the gene RASD1 , which is a component of the corticotropin-releasing hormone receptor signaling system. This finding may provide insight into a novel mechanism involving loss of feedback control to the corticotropin-releasing hormone receptor and subsequent deregulation of ACTH production in corticotroph tumors.
- Subjects :
- Adenoma genetics
Adrenocorticotropic Hormone genetics
Adult
Corticotrophs metabolism
Endosomal Sorting Complexes Required for Transport genetics
Female
Humans
Mutation
Pituitary ACTH Hypersecretion genetics
Pituitary Neoplasms genetics
Receptors, Corticotropin-Releasing Hormone genetics
Sequence Analysis, DNA
Ubiquitin Thiolesterase genetics
ACTH-Secreting Pituitary Adenoma genetics
ras Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2373-2873
- Volume :
- 3
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Cold Spring Harbor molecular case studies
- Publication Type :
- Academic Journal
- Accession number :
- 28487882
- Full Text :
- https://doi.org/10.1101/mcs.a001602