Analysis of the genomic landscape in ALK+ NSCLC patients identifies novel aberrations associated with clinical outcomes

Rearrangements in the anaplastic lymphoma kinase (ALK) gene are found in approximately 5% of non-small cell lung carcinoma (NSCLC). Here, we present a comprehensive genomic landscape of 11 ALK+ NSCLC patients and investigate its relationship with response to crizotinib. Using whole exome sequencing and RNAseq data, we identified 4 rare ALK fusion partners (HIP1, GCC2, ERC1 and SLC16A7), and 1 novel partner (CEP55). At the mutation level, TP53 was the most frequently mutated gene, and was only observed in patients with the shortest progression free survival (PFS). Of note, only 4% of the genes carrying mutations are present in more than one patient. Analysis of somatic copy number aberrations (SCNA) demonstrated that a gain in EML4 was associated with longer PFS and a loss of ALK or gain in EGFR were associated with shorter PFS. This study is the first to report a comprehensive view of the ALK+ NSCLC copy number landscape and to identify SCNA regions associated with clinical outcome. Our data show presence of TP53 mutation as a strong prognostic indication of poor clinical response in ALK+ NSCLC. Furthermore, new and rare ALK fusion partners were observed in the present cohort expanding our knowledge in ALK+ NSCLC.