Comprehensive genomic and clinical analysis of cancer of unknown primary site in Chinese patients

e15071 Background: Cancer of unknown primary (CUP) comprises 2-5% of all diagnosed cancers worldwide and is one of most common cause of death. Deep understanding of CUP plays an imported role in improving the disease diagnoses and finding the primary sites. In this study, our data revealed the genomic and clinical features of CUP in Chinese patients. Methods: FFPE samples and matched peripheral blood were collected for NGS based 450 cancer genes panel assay. Somatic variants were analyzed following CAP/CLIA-certificated workflows, including Single Nucleotide Variant (SNV), Copy Number Variation (CNV), large insertion and deletions (Lindel) and gene rearrangements. MSI status and TMB were also acquired by an NGS algorithm in house. PD-L1 status was analyzed by IHC. Results: Of the 264 CUP patients, 54.2% were male and median age was 61 years old (range, 2-88 years old). The median value of TMB was 4.6 muts/Mb (range, 0-61.2). Only 1 patient was found MSI-H status with the TMB value of 61.2 muts/Mb. In addition, 23.9% and 28.4% of the CUP patients presented PDL1 positive (> 1%) and PDL1 negative respectively, with others unavailable. In the patients of available stage status, they were all advanced stage (stage ≥ III). Top metastatic sites were lymphaden (17.8%), liver(15.9%) and bone (15.5%). TP53 was the most common mutated gene (62.1%), followed by KRAS (22.3%), CDKN2A (15.9%), TERT (10.2%), EGFR (9.8%) and PIK3CA (9.8%). In the alterations of KRAS, G12D, G12V and G12C were occupied 32.2%, 28.8% and 8.4% respectively. Among the alterations of EGFR, 38.5% were L858R and 19.2% were 19del. Besides, amplification of MYC (4.9%) and 11q13 (5.3%) obviously appeared in our data. Fusion/Rearrangements of ALK and ROS1 accounted for 0.8% and 1.1% respectively . The gene alterations of tyrosine kinase were found in 48.4% of CUP patients such as ALK, BRAF, EGFR, FGFR1/2/3/4, RET, ROS1 and so on. PI3K−Akt signaling pathway and MAPK signaling pathway were the most significantly pathways (fdr < 0.001) enriched in our data. A CUP patient with positive PDL1 and high TMB achieved a 9-month PFS after treatment of TP chemotherapy and immunotherapy. Conclusions: In this study, we revealed comprehensive genomic and clinical features of cancer of unknown primary site in Chinese patients. It shows promise to identify the origin anatomic site of tumor while targeted therapeutic approaches to improve outcomes.