Abstract 5742: The landscape of genetic alteration in Chinese lung adenosquamous carcinoma patients
Authors: Wang Hongbiao , Lin Yingcheng , Liu Jun , Cai Yuyin , Qi Xiaofang , Huang Lujia 
Published: June 2022

Background: Lung adenosquamous carcinoma (LASC) is a mixed histologic component tumor type that contains both squamous cell carcinoma and adenocarcinoma, with each component accounting for at least 10% of tumors. The incidence of LASC is very low, only comprising 0.4-4% of all lung cancers. LASC yields a more aggressive clinical course, and its prognosis is generally worse than that of adenocarcinoma and squamous cell carcinoma of the lung. Due to the rarity of LASC, currently, there is no standard treatment. Also, to date, limited genomic data have been performed. In this study, we analyzed the genomic alterations and clinical signatures of LASC.

Materials and Methods: Formalin-fixed, paraffin-embedded (FFPE) tumor tissues and matched blood samples were collected for a 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, and gene fusion and rearrangement were assessed.

Results: A total of 124 LASC patients were enrolled in our study, including 77 (62.1%) males and 47 (37.9%) females, with a median age of 61 years old (range 27-82). Forty-three (43, 34.68%) patients had a smoking history and half of patients possessed a Stage III/IV disease. The most commonly altered genes were TP53 (66.9%), EGFR (54.8%), CDKN2A (21%), TERT (21%), and LRP1B (18.5%). Surprisingly, 91.1% and 52.4% patients harbored at least one druggable alteration based on the solid cancer and NSCLC NCCN guides, respectively. The most frequent druggable mutation, EGFR, is comprised of 35 (51.47%) single mutations and 33 (48.53%) complexed mutations, with most containing a 19 exon deletion and EGFR amplification (12%). The median tumor mutational burden (TMB) of patients with LASC was 5.15 muts/Mb (range, 0-69.3 muts/Mb), and 33 (26.6%) patients were TMB-H (TMB ≥ 10 Muts/Mb). Patients with an ARID2, BRCA1, or KEAP1 mutation had a significantly higher value of TMB than wild type (median TMB 16.1 vs. 5 muts/Mb, 29.7 vs. 5 muts/Mb, 14.6 vs. 4.85 muts/Mb, respectively, P &lt; 0.05). Patients with HRR or DDR mutations also displayed a higher TMB value than for wild type. We additionally determined that mutation signature 1 (the clock-like signature), signature 2 (the APOBEC signature), and signature 3 (the BRCA mutational signature) exhibited a higher mutational load for the entire cohort. All patients with signature 2 or 3 displayed a HLA-B heterozygous subtype.

Conclusions: Our study revealed genomic profiling for the largest sample size of Chinese LASC patients to date. Profiling obtained from this study demonstrates that LASC patients have the same chance for targeted therapy and immune checkpoint inhibitors as compared to lung adenocarcinoma and lung squamous cell carcinoma, respectively.

Citation Format: Hongbiao Wang, Yingcheng Lin, Jun Liu, Yuyin Cai, Xiaofang Qi, Lujia Huang. The landscape of genetic alteration in Chinese lung adenosquamous carcinoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5742.