Abstract 3908: Universal genetic and transcriptomic concordance metrics to validate patient-derived tumor organoid models

• Published in: Cancer research (Chicago, Ill.) Ill.), 2020-08, Vol.80 (16_Supplement), p.3908-3908
• Main Authors: Mapes, Brandon L., Bell, Joshua SK, Langer, Lee F., Huether, Robert, Igartua, Catherine, Sanchez-Freire, Veronica, Tell, Robert, Borgia, Jeffrey A., Masood, Ashiq, Salahudeen, Ameen A.
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2020-3908

Background Patient derived tumor organoids (TOs) are emerging as potential models to elucidate mechanisms of tumor biology and therapeutic response. Here, we establish pan-cancer metrics for validation of genetic and transcriptomic recapitulation, and concordance of an organoid to its native tumor. Methods/Results We sequenced 50 tumor/TO pairs from 12 cancer types using the Tempus xT DNAseq panel and transcriptome RNAseq platforms. Concordance metrics between tumors and TOs were derived for genomic variants called by the DNA xT platform and comparative ratios were calculated for all detected somatic variants. Across all sequenced pairs, somatic variant detection concordance between any mutation identified in primary tissues and tumor organoids resulted in a mean value of 88.1%. Somatic primary tumor variant recapitulation, the percent of somatic variants identified in the primary tumors that were also detected in the TO, averaged 96.3%. In addition to genetic concordance, DNAseq can identify and track clonal and subclonal diversity from source material to TO. In particular, we observed that >90% of source tumor/TO pairs harbor variants with allelic fractions