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01-12-2021 | Pituitary Adenoma | Research article

The genomic profiling and MAMLD1 expression in human and canines with Cushing’s disease

Authors: Andrew Wang, Stewart G. Neill, Scott Newman, Marianna A. Tryfonidou, Adriana Ioachimescu, Michael R. Rossi, Björn P. Meij, Nelson M. Oyesiku

Published in: BMC Endocrine Disorders | Issue 1/2021

Abstract

Background

Cushing’s disease (CD) is defined as hypercortisolemia caused by adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas (corticotroph PA) that afflicts humans and dogs. In order to map common aberrant genomic features of CD between humans and dogs, we performed genomic sequencing and immunostaining on corticotroph PA.

Methods

For inclusion, humans and dog were diagnosed with CD. Whole exome sequencing (WES) was conducted on 6 human corticotroph PA. Transcriptome RNA-Seq was performed on 6 human and 7 dog corticotroph PA. Immunohistochemistry (IHC) was complete on 31 human corticotroph PA. Corticotroph PA were compared with normal tissue and between species analysis were also performed.

Results

Eight genes (MAMLD1, MNX1, RASEF, TBX19, BIRC5, TK1, GLDC, FAM131B) were significantly (P < 0.05) overexpressed across human and canine corticotroph PA. IHC revealed MAMLD1 to be positively (3+) expressed in the nucleus of ACTH-secreting tumor cells of human corticotroph PA (22/31, 70.9%), but absent in healthy human pituitary glands.

Conclusions

In this small exploratory cohort, we provide the first preliminary insights into profiling the genomic characterizations of human and dog corticotroph PA with respect to MAMLD1 overexpression, a finding of potential direct impact to CD microadenoma diagnosis. Our study also offers a rationale for potential use of the canine model in development of precision therapeutics.

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Title: The genomic profiling and MAMLD1 expression in human and canines with Cushing’s disease
Authors: Andrew Wang
Stewart G. Neill
Scott Newman
Marianna A. Tryfonidou
Adriana Ioachimescu
Michael R. Rossi
Björn P. Meij
Nelson M. Oyesiku
Publication date: 01-12-2021
Publisher: BioMed Central
Keyword: Pituitary Adenoma
Published in: BMC Endocrine Disorders / Issue 1/2021
Electronic ISSN: 1472-6823
DOI: https://doi.org/10.1186/s12902-021-00845-z

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Abstract

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