Abstract 2659: Genomic profiling of Chinese adenosquamous carcinoma of the pancreas
Authors: Wang Zheng , Yang Xue , Li Wei , Wu Zheng , Ma Qingyong , Qi Xiaofang , Zhao Juan 
Published: July 2021

Abstract
Background: Adenosquamous carcinoma of the pancreas (PASC) is a mixed tumor type which contains squamous cell carcinoma and also ductal adenocarcinoma components. PASC is a rare type representing about 1-4% of the total incidence. Due to the rarity of this malignancy, limited genomic data have been performed. In this study, we analyzed the genomic alterations and clinical signatures of PASC.
Materials and Methods: Formalin fixed, paraffin embedded (FFPE) tumor tissues and matched blood samples were collected for targeted next-generation sequencing (NGS) assay at OrigiMed (Shanghai, China), a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Genomic alterations including single base substitution, indel, copy number variations, gene fusions and rearrangement were assessed. Tumor mutational burden (TMB) was also analyzed by NGS algorithm. Alterations in homologous recombination repair (HRR) with PASC were analyzed.
Results: In total, 31 PASC patients were recruited included 15 females (48.4%) and 16 males (51.6%) with a media age of 59 years old (range 35-78). A total of 32% (10/31) of patients possessed a confirmed cancer-related family history. The most commonly altered genes were KRAS (97%), TP53 (77%), CDKN2A (35%), SMAD4 (23%), FAT3 (13%), CIC (10%) and SPTA1 (10%). The KEGG pathway analysis revealed that those top mutated genes significantly associated with MAPK signaling pathway. 42% (13/31) of the patients had one or more actionable genomic alterations, including BRCA2, STK11, CDKN2A/B, FGFR and PTEN. Germline mutations were identified in 4 patients (13%), including BRCA2 (2/4), SPINK1 (1/4), FANCA (1/4). The most common mutational type was substitution/Indel (56%), followed by truncation (20%) and gene amplification (17%). Three (10%) patients had at least one mutation in HRR genes, including BRCA2 (2/3) and CHEK2 (1/3).The median TMB of patients with PASC was 3.2 muts/Mb (range, 0.5-9.3 muts/Mb). Patients with STK11 alterations had lower value of TMB than STK11 wild type (median TMB 0.85 vs. 3.37 muts/Mb, respectively, P &lt;0.05). In addition, patients with HRR mutations had a significantly higher TMB value than HRR wild type (7.73 vs. 2.73 muts/Mb, respectively, P &lt;0.01).
Conclusion: Our study revealed the genomic profiling of the largest sample size of Chinese PASC patients so far. 42% (13/31) of the patients had one or more actionable genomic alterations. HRR pathway alterations are relatively frequent (10%) in PASC and consideration for biomarker-enriched clinical trials with PARP, immune checkpoint inhibitors, and novel combinations are warranted.
Citation Format: Zheng Wang, Xue Yang, Wei Li, Zheng Wu, Qingyong Ma, Xiaofang Qi, Juan Zhao. Genomic profiling of Chinese adenosquamous carcinoma of the pancreas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2659.