CANscript™ as a patient-derived predictive platform for individualizing treatment in lung cancer

Abstract

(cancer-cohort, n ¼ 50) or that did not present NSCLC or any other tumors at an advanced age (cancer-free cohort, n ¼ 50). We sequenced their germline DNA using the Agilent Human Exome Capture v5, which includes 21,522 genes (357,999 exons). We selected genetic variants located in the exonic regions and splice sites of the genes evaluated; that codified for non-synonymous codons; and that showed allelic differences >15% between both cohorts. Results: The mean age for the cancer and cancer-free cohorts was 50 (range 34-55) and 78 years (72-90). Mean tobacco consumption was 44 (range 6-72) and 55 pack-years (20-124). Median exome sequencing coverage was 96% at > 10X and median depth was 97X. We identified 229 differential variants between both cohorts, located in 189 genes. The most significant variants (p < 10-4) are shown in the table. Twenty genes or family genes included >3 differential genetic variants (range 3-25): ADAMTS, ALPK2/ 3, ankyrins, APOL4, CCDC, CRIPAK, FYCO1, HLA-A, keratins, mucins, olfactory receptors, PDPR, PRAME family, RFPL2, RP1L1, SAMD9, SLC transporters, anocta-mins, TTN, and ZNF family. Conclusions: We identified genetic variants associated with individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced NSCLC. These variants warrant further study to characterize their impact in the development of these extreme phenotypes. Legal entity responsible for the study: Universidad de Navarra.