Designating eukaryotic orthology via processed transcription units

Orthology is a widely used concept in comparative and evolutionary genomics. In addition to prokaryotic orthology, delineating eukaryotic orthology has provided insight into the evolution of higher organisms. Indeed, many eukaryotic ortholog databases have been established for this purpose. However, unlike prokaryotes, alternative splicing (AS) has hampered eukaryotic orthology assignments. Therefore, existing databases likely contain ambiguous eukaryotic ortholog relationships and possibly misclassify alternatively spliced protein isoforms as in-paralogs, which are duplicated genes that arise following speciation. Here, we propose a new approach for designating eukaryotic orthology using processed transcription units, and we present an orthology database prototype using the human and mouse genomes. Currently existing programs cover less than 69% of the human reference sequences when assigning human/mouse orthologs. In contrast, our method encompasses up to 80% of the human reference sequences. Moreover, the ortholog database presented herein is more than 92% consistent with the existing databases. In addition to managing AS, this approach is capable of identifying orthologs of embedded genes and fusion genes using syntenic evidence. In summary, this new approach is sensitive, specific and can generate a more comprehensive and accurate compilation of eukaryotic orthologs

Cure of unresectable, locally advanced pancreatic cancer after multidisciplinary therapy

The treatment of unresectable, locally advanced pancreatic cancer (ULAPC) is highly challenging as it is considered to be an incurable disease. Our previous studies demonstrated that the combination of gemcitabine, oxaliplatin and 46-h infusion of fluorouracil (5-FU) and leucovorin, the GOFL regimen, is a promising, well-tolerated triplet regimen for locally advanced and recurrent/metastatic pancreatic cancer. Herein, we report a case of ULAPC who remained alive and disease-free for more than five years after a successful, multidisciplinary approach consisting of a 9-month course of induction GOFL, followed by gemcitabine-based concurrent chemoradiotherapy (CCRT) and maintenance GOFL, and subsequently radical R0 resection. This case highlights that prolonged multi-agent chemotherapy with consolidation CCRT can be used to select the patients with ULAPC who may be potential candidates for curative-intent resection, and ultimately even lead to a cure for ULAPC