Abstract 743: Fusion gene identification from common cancer cell lines and comparison to primary tumors

Abstract

Abstract Fusion transcripts, frequently observed in cancer, contribute to oncogenicity by either altering the expression of tumor suppressors/proto-oncogenes or modifying the original function of a protein resulting in an abnormal chimeric protein that stimulates tumorigenesis. Cancer cell lines, extensively used as in-vitro molecular models to study biological processes related to cancer, often do not represent the genomic profiles of primary tumors. To examine the true representation of the cancer cell lines, we examined fusions in tumor- derived cancer cell lines from 20 cancer types in the Cancer Cell Line Encyclopedia (CCLE) and compared them to fusions present in the primary tumors from the TCGA (The Cancer Genome Atlas). ChimeRScope, an alignment-free algorithm developed by our group, was used to screen fusion genes using level 1 paired-end RNA sequencing read data from CCLE and TCGA (GDC data portal). A total of 8,883 primary tumor samples, 730 normal samples spanning 33 cancer types from TCGA, and 802 common laboratory cell lines from CCLE were analyzed in this study. The pool of recurrent fusions identified from CCLE was vastly different from those identified in primary tumors with merely 2% of an overlap. Canonical fusions were found to be more common than non-canonical fusions (fusions containing genes in antisense strand) between TCGA and CCLE. Hierarchical clustering analysis of both canonical and non-canonical recurrent fusions in CCLE and TCGA clustered the primary tumors and cell lines into separate clusters, revealing that fusions in cell lines are vastly different from primary tumors. However, canonical and non-canonical fusion profiles of endometrial cancer cell lines were very similar to female primary tumors (ovarian and breast) and thyroid cancer cell lines were similar to bladder cancer in TCGA. The results from this study indicate that the recurrent fusions in common cancer cell lines harbor fusions that are significantly different from primary tumors. Citation Format: Neetha Nanoth Vellichirammal, Abrar Albahrani, Jasjit K. Banwait, You Li, Babu Guda. Fusion gene identification from common cancer cell lines and comparison to primary tumors [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 743.