Genetic characterisation of molecular targets in carcinoma of unknown primary

Abstract Background Carcinoma of unknown primary (CUP) is a metastatic epithelial malignancy in the absence of an identifiable primary tumour. Prognosis for patients with CUP is poor because treatment options are generally limited to broad spectrum chemotherapy. A shift towards personalised cancer management based on mutation profiling offers the possibility of new treatment paradigms. This study has explored whether actionable, oncogenic driver mutations are present in CUP that have potential to better inform treatment decisions. Methods Carcinoma of unknown primary cases (n = 21) were selected and DNA was isolated from formalin-fixed paraffin embedded sections prior to amplification and sequencing. Two distinct yet complementary targeted gene panels were used to assess variants in up to 76 known cancer-related genes for the identification of biologically relevant and actionable mutations. Results Variants were detected in 17/21 cases (81%) of which 11 (52%) were potentially actionable with drugs currently approved for use in known primary cancer types or undergoing clinical trials. The most common variants detected were in TP53 (47%), KRAS (12%), MET (12%) and MYC (12%). Differences at the molecular level were seen between common CUP histological subtypes. CUP adenocarcinomas and poorly differentiated carcinomas harboured the highest frequency of variants in genes involved in signal transduction pathways (e.g. MET, EGFR, HRAS, KRAS, and BRAF). In contrast, squamous cell carcinoma exhibited a higher frequency of variants in cell cycle control and DNA repair genes (e.g. TP53, CDKN2A and MLH1). Conclusion Taken together, mutations in biologically relevant genes were detected in the vast majority of CUP tumours, of which half provided a potentially novel treatment option not generally considered in CUP

MOESM1 of Genetic characterisation of molecular targets in carcinoma of unknown primary

Additional file 1: Table S1. Combined gene list of the Oncomine Focus Assay (OFA) and Cancer Hotspot v2 (CHPv2) panel (ThermoFisher Scientific)

Fish and invertebrate assemblages in seagrass, mangrove, saltmarsh, and nonvegetated habitats

The original publication can be found at www.springerlink.comMany studies compare utilization of different marine habitats by fish and decapod crustaceans; few compare multiple vegetated habitats, especially using the same sampling equipment. Fish and invertebrates in seagrass, mangrove, saltmarsh, and nonvegetated habitats were sampled during May–August (Austral winter) and December–January (Austral summer) in the Barker Inlet-Port River estuary, South Australia. Sampling was undertaken using pop nets in all habitats and seine nets in seagrass and nonvegetated areas. A total of 7,895 fish and invertebrates spanning 3 classes, 9 orders, and at least 23 families were collected. Only one fish species,Atherinosoma microstoma, was collected in all 4 habitats, 11 species were found in 3 habitats (mangroves, seagrass, and nonvegetated), and 13 species were only caught in seagrass and nonvegetated habitats. Seagrass generally supported the highest numbers of fish and invertebrates and had the greatest species richness. Saltmarsh was at the other extreme with 29 individuals caught from two species. Mangroves and nonvegetated habitats generally had more fish, invertebrates, and species than saltmarsh, but less than seagrass. Analyses of abundances of individual species generally showed an interaction between habitat and month indicating that the same patterns were not found through time in all habitats. All habitats supported distinct assemlages although seagrass and nonvegetated assemblages were similar in some months. The generality of these patterns requires further investigation at other estuaries. Loss of vegetated habitats, particularly seagrass, could result in loss of species richness and abundance, especially for organisms that were not found in other habitats. Although low abundances were found in saltmarsh and mangroves, species may use these habitats for varying reasons, such as spawning, and such use should not be ignored.A. L. Bloomfield and B. M. Gillander