Squamous cell carcinoma of unknown primary (SCCUP): a genomic landscape study

作者：H.R. Robinson, Stephanie Lakritz, Dean C. Pavlick, Sarah Lindsey Davis, Christopher Hanyoung Lieu, Corbin Jeffrey Eule, Laura S Graham, Philippe E. Spiess, Ruichao Li, Ashish M. Kamat, Petros D. Grivas, J M Jacob, Gennady Bratslavsky, Alina Basnet, Kum Thong Wong, Douglas I. Lin, Andrea Necchi, J.S. Ross, Elaine T. Lam · 发表于：ESMO Open · 年份：2025 · DOI：10.1016/j.esmoop.2025.105312 · 被引用次数：7 · 研究领域：Cancer Diagnosis and Treatment、Head and Neck Cancer Studies、Oral Health Pathology and Treatment

BACKGROUND: Squamous cell carcinoma (SCC) of unknown primary (SCCUP) refers to any SCC for which the primary tumor origin cannot be identified despite guideline-directed evaluation. Although strategies employing comprehensive genomic profiling (CGP) to identify targets for non-SCC carcinomas of unknown primary (CUPs) have shown benefit, the genomic landscape in SCCUP remains poorly defined. Here we describe results of CGP in patients with SCCUP to identify potential therapy targets and characteristic biomarkers. PATIENTS AND METHODS: Cases of advanced SCCUP were identified in the FoundationCORE® database by review of clinical history and pathology records. Samples underwent DNA extraction and sequencing to identify genomic alterations (GAs), microsatellite instability (MSI) status, tumor mutational burden (TMB), genomic mutational signatures, and viral reads. Programmed death-ligand 1 (PD-L1) expression was determined by immunohistochemistry. RESULTS: 443 SCCUP cases were identified. Common presentation sites included lymph nodes (41.1%), liver (15.6%), and soft tissue (15.1%). A mean of 6.5 GAs were observed per case. The most frequent non-targetable GAs involved TP53 (62.5%), CDKN2A (37.0%), CDKN2B (19.6%), KMT2D (18.3%), and TERT (16.0%); the most frequent GAs potentially targetable in biomarker-driven trials included PIK3CA (27.3%), PTEN (15.1%), MTAP (13.1%), KRAS (10.4%), and NOTCH1 (8.4%). Among all SCCUP cases, 2.0% had MSI-high (MSI-H) status and 33.9% had TMB ≥10 mu...