ADCY2
Overview
ADCY2 (Adenylate Cyclase 2) encodes a transmembrane adenylyl cyclase that synthesizes cAMP from ATP, functioning downstream of G-protein-coupled receptor signaling. In cancer genomics, ADCY2 has been identified as a recurrent rearrangement target in acral lentiginous melanoma (ALM), where it participates in structural variants including RNA fusions with TERT. Its role as the most-rearranged gene in ALM suggests involvement in aberrant signaling through cAMP-dependent pathways in this melanoma subtype.
Alterations observed in the corpus
- Most-rearranged gene in acral lentiginous melanoma (ALM), affected in 21% of patients (7/34); also participates in a TERT:ADCY2 RNA fusion (patient 12 of 34), representing an interchromosomal structural event linking the TERT reverse-transcriptase locus to ADCY2 PMID:28373299
Cancer types (linked)
- ALM — most-rearranged gene (21%), structural variants including TERT:ADCY2 RNA fusion; observed in a 34-patient ALM WGS cohort PMID:28373299
Co-occurrence and mutual exclusivity
- TERT structural events (including the TERT:ADCY2 fusion) occur in the context of broader TERT dysregulation (41% of ALM patients with somatic/germline TERT aberrations); ADCY2 rearrangements co-occur with the TERT locus PMID:28373299
Therapeutic relevance
- No direct therapeutic targeting of ADCY2 is reported; TERT:ADCY2 fusion patient expressed TERT mRNA, and TERT inhibition (Telomerase Inhibitor IX) was explored as a broader ALM strategy PMID:28373299
Open questions
- Functional consequence of TERT:ADCY2 fusion on ADCY2 signaling and cAMP pathway activity is uncharacterized PMID:28373299
- Whether ADCY2 rearrangements drive oncogenesis independently or solely function to dysregulate TERT expression remains unresolved PMID:28373299
Sources
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