Combining germline, tissue and liquid biopsy analysis by comprehensive genomic profiling to improve the yield of actionable variants in a real-world cancer cohort.

BACKGROUND: Comprehensive next-generation sequencing is widely used for precision oncology and precision prevention approaches. We aimed to determine the yield of actionable gene variants, the capacity to uncover hereditary predisposition and liquid biopsy appropriateness instead of, or in addition to, tumor tissue analysis, in a real-world cohort of cancer patients, who may benefit the most from comprehensive genomic profiling. METHODS: Seventy-eight matched germline/tumor tissue/liquid biopsy DNA and RNA samples were profiled using the Hereditary Cancer Panel (germline) and the TruSight Oncology 500 panel (tumor tissue/cfDNA) from 23 patients consecutively enrolled at our center according to at least one of the following criteria: no available therapeutic options; long responding patients potentially fit for other therapies; rare tumor; suspected hereditary cancer; primary cancer with high metastatic potential; tumor of unknown primary origin. Variants were annotated for OncoKB and AMP/ASCO/CAP classification. RESULTS: The overall yield of actionable somatic and germline variants was 57% (13/23 patients), and 43.5%, excluding variants previously identified by somatic or germline routine testing. The accuracy of tumor/cfDNA germline-focused analysis was demonstrated by overlapping results of germline testing. Five germline variants in BRCA1, VHL, CHEK1, ATM genes would have been missed without extended genomic profiling. A previously undetected BRAF p.V600E mutation was emblematic of the clinical utility of this approach in a patient with a liver undifferentiated embryonal sarcoma responsive to BRAF/MEK inhibition. CONCLUSIONS: Our study confirms the clinical relevance of performing extended parallel tumor DNA and cfDNA testing to broaden therapeutic options, to longitudinally monitor cfDNA during patient treatment, and to uncover possible hereditary predisposition following tumor sequencing in patient care.

Storage temperature effects on blood orange fruit quality.

Orange fruits of two blood varieties (Tarocco and Moro) were stored at 8 degrees C and 22 degrees C for 85 and 106 days, respectively, and analyzed periodically for standard quality parameters (total soluble solids, total acidity, ascorbic acid, juice yield, and rind color) and sensory influencing parameters (anthocyanins, and total and free hydroxycinnamic acids). A decrease in total acidity (TA) and juice yield during storage was observed for both cultivars; total soluble solids (TSS) increased only in the Tarocco oranges stored at 8 degrees C. The increase in TSS observed for Tarocco and the simultaneous decrease in TA in both varieties resulted in a higher maturity index (TSS/TA) for the two cultivars. No loss of vitamin C was noted in Tarocco orange at either temperature, whereas a sharp reduction in vitamin C occurred in the first 50 days of storage for Moro. A significant increase in anthocyanin content was observed in Tarocco and Moro stored at 8 degrees C. Overlong storage induces extensive hydrolysis of hydroxycinnamic derivatives to free acids in Moro orange and these, in turn, could develop the malodorous vinylphenols.