The Analysis Of The Genomic Evolution Of Squamous Cell Carcinoma Of The Lung

Background: Genomic tumor heterogeneity is one reason for recurrence and resistance to cancer therapy. It is still not known what leads to the relapse or the emergence of metastasis in individual patients. To contribute to answer this question, we investigated the evolutionary patterns in squamous cell carcinoma of the lung (SCC) in 10 patients with multiple matched tumors (primary vs recurrence/metastasis). Methods: To identify the genomic profile, frozen tissues from SCC patients were subjected to multiparameter ploidy profiling (MPP). Tumor populations were sorted based on ploidy (DNA-content using DAPI) and p40 was used to control for diploid tumor populations. Subsequent genomic profiling by array comparative genomic hybridization (aCGH) and targeted massive parallel sequencing (Ion Torrent Comprehensive Cancer Panel with an all-exon coverage of 409 cancer genes) was applied. Results: The usage of MPP enabled the determination of the clonal composition of the SCC and define genomic characteristics. Due to flow sorting the tumor populations were effectively isolated and existence of distinct clonal populations was indicated. Aneuploid and diploid tumors were successfully revealed using the additional marker p40. Therefore, the absence of non-malignant cells increased the precision in the genomic analyses Conclusion: The study uncovered the composition of human SCC in the sense of different clonal populations, which harbor private genomic aberrations and mutations confirmed by aCGH and NGS. Even if our data is still preliminary we provide evidence that applying MPP increases the precision of aCGH and sequencing analysis. Genomic analyses of sorted pure tumor population allows to reconstruct the clonal evolution and facilitates the understanding of tumor heterogeneity and their evolutionary pattern, which could have potentially an impact on therapeutic response or metastasis development. Citation Format: Arthur Krause, Thomas Lorber, Valeria Perrina, Tanja Dietsche, Michael Barrett, Christian Ruiz, Lukas Bubendorf. The analysis of the genomic evolution of squamous cell carcinoma of the lung. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 155.