Identification of a novel RASD1 somatic mutation in a USP8 -mutated corticotroph adenoma

Andrew V Uzilov; Khadeen C Cheesman; Marc Y Fink; Leah C Newman; Chetanya Pandya; Yelena Lalazar; Marco Hefti; Mary Fowkes; Gintaras Deikus; Chun Yee Lau; Aye S Moe; Yayoi Kinoshita; Yumi Kasai; Micol Zweig; Arpeta Gupta; Daniela Starcevic; Milind Mahajan; Eric E Schadt; Kalmon D Post; Michael J Donovan; Robert Sebra; Rong Chen; Eliza B Geer

doi:10.1101/mcs.a001602

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Identification of a novel RASD1 somatic mutation in a USP8 -mutated corticotroph adenoma

Journal article

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Identification of a novel RASD1 somatic mutation in a USP8 -mutated corticotroph adenoma

Andrew V Uzilov, Khadeen C Cheesman, Marc Y Fink, Leah C Newman, Chetanya Pandya, Yelena Lalazar, Marco Hefti, Mary Fowkes, Gintaras Deikus, Chun Yee Lau, …

Cold Spring Harbor molecular case studies, Vol.3(3), pp.a001602-a001602

05/2017

DOI: 10.1101/mcs.a001602

PMCID: PMC5411693

PMID: 28487882

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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 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 -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 -mutated tumor, we identified an interesting somatic mutation in the gene , 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.

ras Proteins - genetics

Adenoma - genetics

Pituitary Neoplasms - genetics

Humans

Endosomal Sorting Complexes Required for Transport - genetics

Receptors, Corticotropin-Releasing Hormone - genetics

Ubiquitin Thiolesterase - genetics

Adrenocorticotropic Hormone - genetics

Sequence Analysis, DNA

Pituitary ACTH Hypersecretion - genetics

ACTH-Secreting Pituitary Adenoma - genetics

Adult

Female

Mutation

Corticotrophs - metabolism

Details

Title: Subtitle: Identification of a novel RASD1 somatic mutation in a USP8 -mutated corticotroph adenoma
Creators: Andrew V Uzilov - Department of Genetics and Genomic Sciences and Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA
Khadeen C Cheesman - Division of Endocrinology, Diabetes, and Bone Disease, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA
Marc Y Fink - Department of Genetics and Genomic Sciences and Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA
Leah C Newman - Department of Genetics and Genomic Sciences and Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA
Chetanya Pandya - Department of Genetics and Genomic Sciences and Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA
Yelena Lalazar - Division of Endocrinology, Diabetes, and Bone Disease, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA
Marco Hefti - Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA
Mary Fowkes - Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA
Gintaras Deikus - Department of Genetics and Genomic Sciences and Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA
Chun Yee Lau - Department of Genetics and Genomic Sciences and Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA
Aye S Moe - Department of Genetics and Genomic Sciences and Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA
Yayoi Kinoshita - Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA
Yumi Kasai - Department of Genetics and Genomic Sciences and Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA
Micol Zweig - Department of Genetics and Genomic Sciences and Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA
Arpeta Gupta - Division of Endocrinology, Diabetes, and Bone Disease, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA
Daniela Starcevic - Department of Genetics and Genomic Sciences and Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA
Milind Mahajan - Department of Genetics and Genomic Sciences and Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA
Eric E Schadt - Department of Genetics and Genomic Sciences and Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA
Kalmon D Post - Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA
Michael J Donovan - Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA
Robert Sebra - Department of Genetics and Genomic Sciences and Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA
Rong Chen - Department of Genetics and Genomic Sciences and Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA
Eliza B Geer - Multidisciplinary Pituitary and Skull Base Tumor Center, Memorial Sloan Kettering, New York, New York 10065, USA
Resource Type: Journal article
Publication Details: Cold Spring Harbor molecular case studies, Vol.3(3), pp.a001602-a001602
DOI: 10.1101/mcs.a001602
PMID: 28487882
PMCID: PMC5411693
NLM abbreviation: Cold Spring Harb Mol Case Stud
ISSN: 2373-2873
eISSN: 2373-2873
Publisher: United States
Language: English
Date published: 05/2017
Academic Unit: Pathology; Iowa Neuroscience Institute
Record Identifier: 9984047735002771

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