Abstract 1059: Precision medicine in a community cancer center: pan-cancer DNA/RNA sequencing of tumors reveals clinically relevant gene fusions
Authors: Darabi Sourat , Braxton David R. , Zuazo Carlos E. , Eisenberg Burton L. , Demeure Michael J. 
Published: June 2023

Background: Gene fusions occur when two independent genes form a hybrid gene through genomic rearrangements, which often leads to abnormal expression and function of the encoded proteins. In hematological and solid cancers, oncogenic fusions may be prognostic, diagnostic, or therapeutic biomarkers. Improved detection and understanding of the functional implications of such fusions may be beneficial for patient care. Herein, we report gene fusions in different solid tumors seen in a community cancer center.

Method: We retrospectively analyzed our internal genomic cancer center-specific cBioPortal database for gene fusions identified by DNA and RNA sequencing of solid tumors through a CLIA/CAP commercial lab from 2016-2022. We divided the identified fusions into two groups: 1) known oncogenic fusions; and 2) unclassified fusions.

Results: We identified 420 known oncogenic fusions in 4,415 tumors. Oncogenic fusions occurred most often in ovarian adenocarcinoma (N=62/420; 14.8%), followed by non-small cell lung cancer (NSCLC) (N=55/420; 13.1%), prostate cancer (N=48/420; 11.4%), breast cancer (N=46/420; 10.1%), glioblastoma (N=35/420; 8.3%), and colorectal cancer (N=22/420; 5.2%). We identified EML4-ALK fusions in 13 tumor samples and KIF5B-RET fusions in 9 tumors, all in NSCLC. We identified 18 fusions in soft tissue sarcomas, including the fusions that are the hallmark of synovial sarcomas, such as SS18-SSX1 and SS18-SSX2. In addition, we identified 25 unclassified fusions (Table).

Conclusions: 9.5% of our tumors have oncogenic fusions that may be clinically relevant, which suggests patients with advanced cancers should have comprehensive molecular profiling that includes RNA sequencing. Additional studies are needed to determine the function of the identified unclassified gene fusions to assess potential clinical significance.

Table- Unclassified Fusions (number per total unclassified fusions) Tumor Type (Total Number of Samples Profiled) Fusion Positive samples Unclassified Fusions Prostate adenocarcinoma (89) 8 (32%) BMPR1B-PDLIM5 (2 patients), CDC13-SUGCT, NIPBL-RAI14, TTC6-MIPOL1, NFIB-UBE3B, GALNT7-SPOCK3, TBCA-AP3B1 Breast cancer (224) 8 (32%) NIPBL-PIEZO1, ETV6-RINT1, PAK1-TEX14, PAK1-MMP20, PAK1-LOC101928896, TTC6-MIPOL1, BMPR1B-PDLIM5, CMTM8-OSBPL10 Non-small cell lung cancer (751) 4 (16%) PANX1-PRPF19 (2 patients), TTC6-MIPOL1, GALNT7-SMIM8 Head and neck cancer (177) 2 (8%) ETV6-DNAH14, TP53BP1-SND1 Salivary gland tumor (22) 1 (4%) NFIB-CHCHD7 Pancreatic adenocarcinoma (186) 1 (4%) CMTM8-GPD1L Ovarian cancer (362) 1 (4%) NIPBL-SLC1A3 Total Number of Fusions 25

Citation Format: Sourat Darabi, David R. Braxton, Carlos E. Zuazo, Burton L. Eisenberg, Michael J. Demeure. Precision medicine in a community cancer center: pan-cancer DNA/RNA sequencing of tumors reveals clinically relevant gene fusions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1059.