Translating RNA sequencing into clinical diagnostics: opportunities and challenges

The 21-gene recurrence score (RS) assay quantifies the likelihood of distant recurrence in women with estrogen receptor-positive, lymph node-negative breast cancer treated with adjuvant tamoxifen. The relationship between the RS and chemotherapy benefit is not known. The RS was measured in tumors from the tamoxifen-treated and tamoxifen plus chemotherapy-treated patients in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B20 trial. Cox proportional hazards models were utilized to test for interaction between chemotherapy treatment and the RS. A total of 651 patients were assessable (227 randomly assigned to tamoxifen and 424 randomly assigned to tamoxifen plus chemotherapy). The test for interaction between chemotherapy treatment and RS was statistically significant (P = .038). Patients with high-RS (> or = 31) tumors (ie, high risk of recurrence) had a large benefit from chemotherapy (relative risk, 0.26; 95% CI, 0.13 to 0.53; absolute decrease in 10-year distant recurrence rate: mean, 27.6%; SE, 8.0%). Patients with low-RS (< 18) tumors derived minimal, if any, benefit from chemotherapy treatment (relative risk, 1.31; 95% CI, 0.46 to 3.78; absolute decrease in distant recurrence rate at 10 years: mean, -1.1%; SE, 2.2%). Patients with intermediate-RS tumors did not appear to have a large benefit, but the uncertainty in the estimate can not exclude a clinically important benefit. The RS assay not only quantifies the likelihood of breast cancer recurrence in women with node-negative, estrogen receptor-positive breast cancer, but also predicts the magnitude of chemotherapy benefit.

The 14th St Gallen International Breast Cancer Conference (2015) reviewed new evidence on locoregional and systemic therapies for early breast cancer. This manuscript presents news and progress since the 2013 meeting, provides expert opinion on almost 200 questions posed to Consensus Panel members, and summarizes treatment-oriented classification of subgroups and treatment recommendations.

Transfer RNAs (tRNAs) represent the single largest, best-understood class of non-protein coding RNA genes found in all living organisms. By far, the major source of new tRNAs is computational identification of genes within newly sequenced genomes. To organize the rapidly growing collection and enable systematic analyses, we created the Genomic tRNA Database (GtRNAdb), currently including over 74 000 tRNA genes predicted from 740 species. The web resource provides overview statistics of tRNA genes within each analyzed genome, including information by isotype and genetic locus, easily downloadable primary sequences, graphical secondary structures and multiple sequence alignments. Direct links for each gene to UCSC eukaryotic and microbial genome browsers provide graphical display of tRNA genes in the context of all other local genetic information. The database can be searched by primary sequence similarity, tRNA characteristics or phylogenetic group. The database is publicly available at http://gtrnadb.ucsc.edu.