Serial analysis of gene expression in adrenocortical hyperplasia caused by a germline PRKAR1A mutation.
BACKGROUND
Adrenocortical tumors have been studied at the molecular genetic and cytogenetic levels, but the gene expression profiles of normal and tumor adrenal tissue have not been extensively investigated.


OBJECTIVE
The objective of this study was to obtain information about transcriptome differences in hyperplastic adrenal cells.


METHODS
We performed serial analysis of gene expression (SAGE) on control adrenal tissue and primary pigmented nodular adrenocortical disease (PPNAD) tissue from two adolescent female patients.


METHODS
The main outcome measure was to provide quantitative datasets of the vast majority of the transcripts implicated in normal and pathogenic adrenal functioning.


RESULTS
The libraries of 28,705 and 31,278 tags represented 14,846 and 16,698 unique mRNAs from the control and PPNAD tissue, respectively. A total of 842 tags from the two libraries did not match any known sequences. We found 127 tags, including 70 no-match tags, to be expressed almost exclusively in control and/or PPNAD adrenals and to be absent or very rare in other human tissues. Examples of well-characterized genes expressed at significantly higher levels in PPNAD included steroidogenic acute regulator, chromogranin A, and those coding for the steroidogenic enzymes P450 cytochromes CYP17A1 and CYP21A2. Pathway analysis revealed Wnt signaling as the most up-regulated in PPNAD. These data were confirmed for selected genes by quantitative RT-PCR and/or immunohistochemistry.


CONCLUSIONS
This study was the first of its kind for adrenal tissue and provides important information about the adrenal transcriptome and aberrant signaling in an inherited form of adrenocortical hyperplasia.
Horvath
Anelia
A
Section on Endocrinology and Genetics, Developmental Endocrinology Branch, National Institute of Child Health and Human Development/NIH, Building 10, Clinical Research Center, Room I-1330, 10 Center Drive, MSC 1103, Bethesda, MD 20892-1103, USA.
Mathyakina
Ludmila
L
Vong
Queenie
Q
Baxendale
Vanessa
V
Pang
Alan L Y
AL
Chan
Wai-Yee
WY
Stratakis
Constantine A
CA
D000306:Adrenal Cortex Neoplasms / Q000235:genetics* / Q000378:metabolism; D002648:Child; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; D017868:Cyclic AMP-Dependent Protein Kinases; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D015723:Gene Library; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; C517834:PRKAR1A protein, human; D011506:Proteins; D012333:RNA, Messenger; D017868:Cyclic AMP-Dependent Protein Kinases