P2.03b-029 Analysis of Genomic Alterations and Heterogeneity in Pulmonary Adenoid Cystic Carcinoma by Next-Generation Sequencing: Topic: Biomarkers

Abstract

Pulmonary adenoid cystic carcinoma (PACC) is one of the rare malignancies, that primary from glandular tissues of lung. Currently, the treatment of PACC relies on surgery and local radiotherapy. However the therapy for advanced PACC patients is limited. A larger number of studies demonstrated that advanced PACC patients obtained little benefit from chemotherapy. Moreover, only a few case reports revealed PACC patients were appropriate for target therapy. Using high-flux and high-resolution techniques to detect the genomic alterations of PACC could provide theoretical foundation for the precision therapy of PACC. 8 PACC patients who received surgical resection between January 2013 and December 2015 were enrolled. The tumor tissues from different locations and blood samples were collected. The oncoscreenTM panel by Illumina platform, which utilizing probe hybridization to gathering 287 exon regions and 22 intron regions, were used to detect the gene mutation status of PACC. And the embryonal system mutations were filtered by contrasting the gene mutation status of the leukocytes. The tumor heterogeneity was revealed by comparing the gene mutation status in different areas of the same PACC, and the phylogenetic relationships were analyzed to disclose the evolving and developing progression of PACC. There were 69 gene mutations together among 8 patients including 29 samples. Each patient has 8.6 mutations averagely. The high-frequency mutations were PAK3-D219E, FBXW7-D112E, TET2-T418I, KAT6A-E796A, and MET-R1005Q. However, the common mutations in other NSCLC, like EGFR, KRAS, ALK, etc., weren’t happened in this group of PACC. In this study, the spatial heterogeneity was discovered in PACC, not only in the mutation site, but also in the mutant abundance. Moreover, the phylogenetic relationships revealed that the clonal evolution and development existed in PACC. The status of genomic alterations in PACC was different from the other non-small cell lung cancer (NSCLC). PACC showed obvious spatial heterogeneity and clonal evolution.