Abstract 3400: Comprehensive genomic profiling in Chinese patients with pulmonary sarcomatoid carcinoma

Abstract

Abstract Background:Pulmonary sarcomatoid carcinoma (PSC) is a unique type of lung tumor with low incidence and poor prognosis. There is no standard treatment for advanced PSC patients. Most of them refer to NSCLC chemotherapy. The molecular characteristic of PSC was not as clear as other histological subtypes of NSCLC. Comprehensive genomic analysis of PSC would provide guidance for targeted and immune therapies. Methods:Next generation sequencing (NGS) targeting 450 cancer genes was performed on FFPE and matched blood samples collected from 13 Chinese PSC patients (16 samples). Genomic alterations (GAs) including single nucleotide variations, short and long insertions and deletions, copy number variations, and gene rearrangements were analyzed. Microsatellite instability (MSI) status was assessed by NGS algorithms. Tumor tissues were analyzed for PDL1 expression by immunohistochemistry (IHC) staining. . Results:The median age of PSC patients was 63 years (range 32-79), among them 10 were male and 3 were female. Average of 12.4 GAs /sample and 2.2 actionable GAs/sample were detected. The most frequently mutated genes were TP53 (10/13), PDGFRA (4/13), KRAS (3/13), MET (3/13), BAP1 (3/13), SPTA1 (3/13), FAT3 (3/13), LRP1B (3/13). In seven of the 13 patients (53.8%), two or more gene variants were co-existed, with up to five mutations in a single case. RB1 and KRAS alterations were found only in TP53-mut cases. The frequencies of the seven genes recommended by NCCN guidelines for NSCLC were MET (3/13), BRAF (2/13), EGFR (2/13), ALK(1/13), respectively. No RET, HER2 and ROS1 variations were found. Notably, the genomic alteration frequencies of MET and BRAF were higher compared with that in other NSCLC (MET: 4.9%, BRAF: 4.4%). MET exon 14 alterations including splice point mutation (c.3028+1G>C) and point mutation (D1010Y) were identified in two patients. BRAF and EGFR mutations occurred in PSC patients were all hotspot including V600E for BRAF and exon 19 deletion and L858R for EGFR. The variations of ALK include gene rearrangement and point mutation (A1200V). In addition, other potential therapeutic targets were also detected: PDGFRA (4/13), PIK3CA(2/13), PTEN (1/13), FGFR1 (1/13) and CDKN2A (1/13). MSI status was evaluated in 12 patients, and all the 12 patients were MSS. PD-L1 IHC assay was only performed in 4 available patients, and 3 patients were PD-L1 positive and 1 patient was PD-L1 negative. More pts will be collected and involved in the study. Conclusion: Chinese PSC patients have multiple genomic alterations that can be targeted for treatments. The proportion of MET exon 14 mutations in PSC was higher, which was consistent with previous literatures. Therefore, the use of full-scale genome sequencing to explore potential therapeutic targets can help PSC patients benefit from potential targeted therapy and immunotherapy. Citation Format: Rong Shen, Fabo Qiu, Hao Zou, Lixin Li, Bin Yue, Zhihao Lu, Hanxia Han, Lijuan Chen, Lin Zhang. Comprehensive genomic profiling in Chinese patients with pulmonary sarcomatoid carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3400.