Whole-genome and transcriptome analysis enhances precision cancer treatment options.

BACKGROUND: Recent advances are enabling delivery of precision genomic medicine to cancer clinics. While the majority of approaches profile panels of selected genes or hotspot regions, comprehensive data provided by whole-genome and transcriptome sequencing and analysis (WGTA) present an opportunity to align a much larger proportion of patients to therapies. PATIENTS AND METHODS: Samples from 570 patients with advanced or metastatic cancer of diverse types enrolled in the Personalized OncoGenomics (POG) program underwent WGTA. DNA-based data, including mutations, copy number and mutation signatures, were combined with RNA-based data, including gene expression and fusions, to generate comprehensive WGTA profiles. A multidisciplinary molecular tumour board used WGTA profiles to identify and prioritize clinically actionable alterations and inform therapy. Patient responses to WGTA-informed therapies were collected. RESULTS: Clinically actionable targets were identified for 83% of patients, of which 37% of patients received WGTA-informed treatments. RNA expression data were particularly informative, contributing to 67% of WGTA-informed treatments; 25% of treatments were informed by RNA expression alone. Of a total 248 WGTA-informed treatments, 46% resulted in clinical benefit. RNA expression data were comparable to DNA-based mutation and copy number data in aligning to clinically beneficial treatments. Genome signatures also guided therapeutics including platinum, poly-ADP ribose polymerase inhibitors and immunotherapies. Patients accessed WGTA-informed treatments through clinical trials (19%), off-label use (35%) and as standard therapies (46%) including those which would not otherwise have been the next choice of therapy, demonstrating the utility of genomic information to direct use of chemotherapies as well as targeted therapies. CONCLUSIONS: Integrating RNA expression and genome data illuminated treatment options that resulted in 46% of treated patients experiencing positive clinical benefit, supporting the use of comprehensive WGTA profiling in clinical cancer care.

Testing the utility of the newest vital sign (NVS) health literacy assessment tool in older African-American patients.

OBJECTIVE: To evaluate utility of the newest vital sign (NVS) which can be completed in 3min compared to the short version test of functional literacy in adults (S-TOFHLA) that takes 7min for health literacy in the older African American patients. METHODS: We enrolled 62 older (age>65 years) African American patients and administered the NVS and the S-TOFHLA. A score of less than 4 for the NVS and less than 16 for the S-TOFHLA was indicative of limited health literacy. RESULTS: Mean age of our patients was 73.2+7.9 years with an average education level of twelfth grade. Using S-TOFHLA 51% of the subjects were deemed to be sufficiently literate, with a score of 23.0+8.6 compared to 56% on the NVS with a score of 3.0+1.9. The average time for completing the NVS was 11min in our patient population. CONCLUSION: Based on our data, while health literacy level can be assessed with the NVS its practicality as a quick screening tool in the elderly population appears limited. PRACTICE IMPLICATIONS: Knowing the level of patient's health literacy may help physicians deliver health information in the format that patients can understand.

Effect of streptomycin on lipid composition with particular reference to cyclic depsipeptide biosynthesis in Serratia marcescens and other micro-organisms.

The addition of low concentrations of streptomycin (5-10mug/ml of medium) to Serratia marcescens caused significant alterations in the lipid composition of this organism, but neither growth nor pigmentation was affected. The acetone-soluble cyclic depsipeptides, which comprise on average 15% of the total lipid, were decreased almost to zero and the total lipid phosphorus was more than doubled in the presence of streptomycin. Most of the phospholipid increase was due to an increase in phosphatidylethanolamine. Cyclic depsipeptides were not leached from the cell in the presence of streptomycin, indicating a definite inhibition of the biosynthetic pathway. The effect of streptomycin on the reported peptidolipids of Rhodopseudomonas spheroides, Halobacterium halobium, Nocardia asteroides and Pseudomonas tabaci was investigated. In the case of the only strictly comparable cellular cyclic depsipeptide (that of N. asteroides) the biosynthesis was strongly inhibited by streptomycin, but cell weight was maintained or even slightly increased. A possible mode and site of action of low concentrations of streptomycin on bacterial lipids is discussed.