What is the clinical evidence from this study?

Study design: Other. Population: Benign lesions of the adrenal cortex (PPNAD, AIMAH/MMAD, McCune-Albright syndrome) (n=6). Intervention: Somatic GNAS mutations vs. Germline PRKAR1A mutations. Primary outcome: Enrichment for extracellular matrix receptor interaction pathway (fold enrichment 3.5, p=<0.0001).

January 19, 2012The Journal of Clinical Endocrinology & Metabolism

Activation of Cyclic AMP Signaling Leads to Different Pathway Alterations in Lesions of the Adrenal Cortex Caused by Germline PRKAR1A Defects versus Those due to Somatic GNAS Mutations

Q: What are the key findings of this study?

Adrenal lesions harboring somatic GNAS mutations were significantly enriched for extracellular matrix receptor interaction and focal adhesion pathways compared to those with germline PRKAR1A mutations.

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Key result

Adrenal lesions harboring somatic GNAS mutations were significantly enriched for extracellular matrix receptor interaction and focal adhesion pathways compared to those with germline PRKAR1A mutations.

Population

Normal (pooled) adrenals, PRKAR1A-mutant (n=3) and GNAS-mutant (n=3) adrenal lesions

Comparison

Whole-genome expression profiling (WGEP) vs Normal adrenal tissue and comparison between…

Design

Preclinical

Authors

MAMadson Q. AlmeidaUniversidade de São Paulo MAMonalisa Ferreira AzevedoUniversidade de Brasília PXParaskevi XekoukiUniversity of Crete

Discussion

Member takes

Implication

Animal data on divergent adrenal pathways warrant no practice change; leaves open mutation-specific therapeutic targets pending human validation.

Structured PICO

Population

6 patients with benign lesions of the adrenal cortex caused by germline PRKAR1A defects or somatic GNAS mutations whose tissues were analyzed for whole-genome expression profiles.

Exposure

Whole-genome expression profiling (WGEP)

Comparator

Normal adrenal tissue and comparison between PRKAR1A- and GNAS-mutant lesions

Outcome

Gene expression profiles and pathway alterationssurrogate

Main Result

Effect estimate: fold enrichment 3.5

p-value: p=<0.0001

Adrenal lesions with PRKAR1A or GNAS mutations share some downstream oncogenic signals but differ substantially in other pathway alterations despite both involving cAMP activation.

Limitations

Small sample size of 3 lesions per group

Cite This Study

Almeida et al. (2012) studied Benign lesions of the adrenal cortex (PPNAD, AIMAH/MMAD, McCune-Albright syndrome) (n=6). Somatic GNAS mutations vs. Germline PRKAR1A mutations was evaluated on Enrichment for extracellular matrix receptor interaction pathway (fold enrichment 3.5, p=<0.0001). Adrenal lesions harboring somatic GNAS mutations were significantly enriched for extracellular matrix receptor interaction and focal adhesion pathways compared to those with germline PRKAR1A mutations.

synapsesocial.com/papers/6a8714b0ddd5671cb07ccbb6 https://doi.org/10.1210/jc.2011-3000

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Implication

Animal data on divergent adrenal pathways warrant no practice change; leaves open mutation-specific therapeutic targets pending human validation.

Activation of Cyclic AMP Signaling Leads to Different Pathway Alterations in Lesions of the Adrenal Cortex Caused by Germline PRKAR1A Defects versus Those due to Somatic GNAS Mutations

Discussion

Member takes

Implication

Structured PICO

Main Result

Limitations

Cite This Study

Activation of Cyclic AMP Signaling Leads to Different Pathway Alterations in Lesions of the Adrenal Cortex Caused by Germline PRKAR1A Defects versus Those due to Somatic GNAS Mutations

Discussion

Member takes

Implication

Structured PICO

Main Result

Limitations

Cite This Study

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