Exploring how gene mutations in tumors impact radiation sensitivity northwesternu
Purpose: Large-scale sequencing efforts have established that cancer-associated genetic alterations are highly diverse, posing a challenge to the identification of variants that regulate complex phenotypes like radiation sensitivity. The impact of the vast majority of rare or common genetic variants on the sensitivity of cancers to radiotherapy remains largely unknown.
Variants were prioritized based on genotype-phenotype associations from a previously completed large-scale cancer cell line radiation profiling study. Altogether, 488 alleles from 92 genes were generated and profiled in an immortalized lung cell line, BEAS-2B. We validated our results in other cell lines ,via the use of both cell line and patient-derived murine xenografts, and in clinical cohorts.
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