Molecular subtyping of adrenocortical carcinoma reveals distinct subtypes with prognostic and therapeutic implications
The authors report that adrenocortical carcinoma can be stratified into distinct molecular subtypes with prognostic and therapeutic implications and that targeted treatment options may differ by subtype.
Adrenocortical carcinoma (ACC) is a rare but aggressive malignancy with poor survival and limited treatment options. We performed an integrated genomic analysis on 61 Chinese patients with ACC and identified recurrent mutations in TP53 (25%), CTNNB1 (15%), ZNRF3 (10%) and MEN1 (8%). Unsupervised clustering of transcriptomic data revealed four distinct molecular subtypes: cortisol‑driven (CD), immune‑suppressed (IS), cell‑cycle‑altered (CCA) and immunomodulatory (IM). Copy‑number analysis uncovered focal amplifications (TERT, CDK4) and HLA‑II deletions. The study proposes subtype‑specific therapeutic strategies, such as CDK4/6 inhibition for CCA and immunotherapy for IM tumors.
Understanding the molecular heterogeneity of ACC could guide precision therapies and improve outcomes for this aggressive, treatment‑refractory cancer.
Evidence level: Sejtvonalas. Laboratóriumi sejtekben vizsgálták.
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