We show the following: 1) aHIF is a natural antisense transcript derived from HIF1alpha gene sequences encoding the 3' untranslated region of HIF1alpha mRNA; 2) aHIF is specifically overexpressed in all nonpapillary clear-cell renal carcinomas examined, but not in the papillary renal carcinomas examined; 3) aHIF is overexpressed in an established nonpapillary renal carcinoma cell line under both normoxic (i.e., normal aerobic) and hypoxic conditions; and 4) although aHIF is not further induced by hypoxia in nonpapillary disease, it can be induced in lymphocytes where there is a concomitant decrease in HIF1alpha mRNA. To our knowledge, this is the first case of overexpression of a natural antisense transcript exclusively associated with a specific human malignant disease.

The von Hippel-Lindau locus on chromosome 3p is a tumor suppressor gene known to be involved in nonpapillary renal cell carcinoma. A previous loss of heterozygosity (LOH) study aimed at determining the allelotype of kidney tumors has indicated that in addition to 3p, chromosome arms 5q, 6q, 10q, llq, 17p, and i9p may also harbor tumor suppressor genes. However, cytogenetic studies reveal that chromosomes 3p, 6q, 8p, 9pq, and 14q most frequently undergo karyotypic changes in renal tumors. To resolve these differences, a collection of microsatellite DNA probes has been used to scan for LOH so that 90%o of individual tumor genomes were rendered informative for allele loss. The assay is capable of detecting quantitative genomic alterations in tumor cells as well. We find that LOH is most frequent for chromosome arm 3p. However, in no tumor is 3p exclusively affected. LOH for 6q, 8p, 9pq, and 14q is also distinctly elevated for both nonpapillary as well as papillary tumors and suggest that many of the tumor suppressor loci involved may be common to the etiology of both forms of kidney cancer.

Background Circulating tumor cells (CTC) and plasma cell-free RNA (cfRNA) can serve as biomarkers for prognosis and treatment response in lung cancer. One barrier to the selected or routine use of CTCs and plasma cfRNA in precision oncology is the limited quantity of both, and CTCs are only seen in metastatic disease. As capture of CTCs and plasma cfRNA presents an opportunity to monitor and assess malignancies without invasive procedures, we compared two methods for CTC capture and identification, and profiled mRNA from CTCs and plasma cfRNA to identify potential tumor-associated biomarkers. Methods Peripheral blood was collected from ten patients with small cell lung cancer (SCLC), ten patients with non-small cell lung cancer (NSCLC) and four healthy volunteers. Two methods were used for CTC capture: the standard epithelial cell adhesion molecule (EpCam) CellSearch kit (unicapture) and EpCAM plus HER2, EGFR and MUC-1 specific combined ferrofluid capture (quadcapture). For the quadcapture, anti-cytokeratin 7 (CK7) was additionally used to assist in CTC identification. NanoString analysis was performed on plasma cfRNA and on mRNA from combined ferrofluid isolated CTCs. Expression data was analyzed using STRING and Reactome. Results Unicapture detected CTCs in 40% of NSCLC and 60% of SCLC; whereas, quadcapture/CK7 identified CTCs in 20% of NSCLC and 80% of SCLC. Bioinformatic analysis of NanoString data identified high expression of a platelet factor 4 (PF4)-related group of transcripts. Conclusions Quadcapture ferrofluid reagent did not significantly improve CTC capture efficacy. NanoString analysis based on CTC and plasma cfRNA data highlighted an intriguing PF-4-centric network in patients with metastatic lung cancer. Electronic supplementary material The online version of this article (10.1186/s12885-019-5795-x) contains supplementary material, which is available to authorized users.

Objectives-Development of targeted therapies for pancreatic cancer could be enhanced by a reliable method for noninvasive tumor cell assessment. In this pilot study we isolated and phenotypically characterized circulating tumor cells (CTC) from patients with metastatic pancreatic cancer and explored their relationship to clinical outcome.Methods-Peripheral blood from 50 patients was collected at treatment initiation and first disease evaluation for CTC enumeration and phenotyping by CellSearch® system. Expression of human mucin 1 (MUC-1) was performed.Results-48 and 37 patients had evaluable samples at baseline and first disease evaluation, respectively. The cohort was 62% male, with a median age of 63 years. At least 1 CTC/7.5mL was detected in 23 patients (48%) pre-treatment and 11 patients (30%) at first disease evaluation. No difference was seen in overall survival between patients with ≥ 1 CTC vs no CTC at baseline (p=0.14). Patients with MUC-1 expressing CTC (n=10) had shorter median overall survival compared to those with MUC-1 negative CTC (n=13) (2.7 vs. 9.6m; p=0.044).Conclusions-CTC enumeration and phenotypic characterization from metastatic pancreatic cancer patients is feasible. No correlation was found between CTC isolation and survival. However, the presence of MUC-1 expressing CTC demonstrated a trend toward inferior survival.

Rotating-gel electrophoresis and DNA hybridization were used to compare the electrophoretic karyotype of six Candida albicans isolates. The hybridization pattern for 22 cloned sequences, including eight previously unmapped genes, indicates that there are eight pair of homologous chromosomes in each strain. However, since homologous chromosomes can differ in length, it is possible to resolve more than eight bands in some strains. The mapping data demonstrate that linkage groups are generally conserved suggesting that, in spite of gross karyotype differences, there is an underlying similarity in the genome organization of different isolates. The hybridization data also provide direct evidence that DNA translocations and reciprocal translocations contribute to chromosome length polymorphisms in C. albicans.