Development and Clinical Validation of a Blood Test for Early Detection of Colorectal Adenomas and Cancer for Screening and Postpolypectomy Surveillance.

Background And Aims: There is a lack of convenient, sensitive, noninvasive strategies for screening and surveillance for colorectal neoplasia. An assay combining the results of circulating epithelial cells (CECs) and somatic mutations of cell-free DNA adjusting for age/sex using a unique algorithm is evaluated in patients requiring colonoscopy.

Methods: A prospective single-site 458-subject study (asymptomatic: 43% screening/43% surveillance, enriched with 65 symptomatic subjects undergoing colonoscopy) was conducted.

Analytical validation of the CellMax platform for early detection of cancer by enumeration of rare circulating tumor cells.

The CellMax (CMx®) platform was developed to enrich for epithelial circulating tumor cells (CTCs) in the whole blood. This report provides assay performance data, including accuracy, linearity, limit of blank, limit of detection (LOD), specificity, and precision of enumeration of cancer cell line cells (CLCs) spiked in cell culture medium or healthy donor blood samples. Additionally, assay specificity was demonstrated in 32 young healthy donors and clinical feasibility was demonstrated in a cohort of 47 subjects consisting of healthy donors and patients who were colonoscopy verified to have colorectal cancer, adenomas, or a negative result.

Genome-wide DNA methylation measurements in prostate tissues uncovers novel prostate cancer diagnostic biomarkers and transcription factor binding patterns.

Background: Current diagnostic tools for prostate cancer lack specificity and sensitivity for detecting very early lesions. DNA methylation is a stable genomic modification that is detectable in peripheral patient fluids such as urine and blood plasma that could serve as a non-invasive diagnostic biomarker for prostate cancer.

Methods: We measured genome-wide DNA methylation patterns in 73 clinically annotated fresh-frozen prostate cancers and 63 benign-adjacent prostate tissues using the Illumina Infinium HumanMethylation450 BeadChip array.

NUSAP1 expression is upregulated by loss of RB1 in prostate cancer cells.

Background: Overexpression of NUSAP1 is associated with poor prognosis in prostate cancer, but little is known about what leads to its overexpression. Based on previous observations that NUSAP1 expression is enhanced by E2F1, we hypothesized that NUSAP1 expression is regulated, at least in part, by loss of RB1 via the RB1/E2F1 axis.

Methods: Using Significance Analysis of Microarrays, we examined RB1, E2F1, and NUSAP1 transcript levels in prostate cancer gene expression datasets.

Novel fusion transcripts associate with progressive prostate cancer.

The mechanisms underlying the potential for aggressive behavior of prostate cancer (PCa) remain elusive. In this study, whole genome and/or transcriptome sequencing was performed on 19 specimens of PCa, matched adjacent benign prostate tissues, matched blood specimens, and organ donor prostates. A set of novel fusion transcripts was discovered in PCa.

Increased expression of GCNT1 is associated with altered O-glycosylation of PSA, PAP, and MUC1 in human prostate cancers.

Background: Protein glycosylation is a common posttranslational modification and glycan structural changes have been observed in several malignancies including prostate cancer. We hypothesized that altered glycosylation could be related to differences in gene expression levels of glycoprotein synthetic enzymes between normal and malignant prostate tissues.

Methods: We interrogated prostate cancer gene expression data for reproducible changes in expression of glycoprotein synthetic enzymes.

mRNA-Seq of single prostate cancer circulating tumor cells reveals recapitulation of gene expression and pathways found in prostate cancer.

Circulating tumor cells (CTC) mediate metastatic spread of many solid tumors and enumeration of CTCs is currently used as a prognostic indicator of survival in metastatic prostate cancer patients. Some evidence suggests that it is possible to derive additional information about tumors from expression analysis of CTCs, but the technical difficulty of isolating and analyzing individual CTCs has limited progress in this area. To assess the ability of a new generation of MagSweeper to isolate intact CTCs for downstream analysis, we performed mRNA-Seq on single CTCs isolated from the blood of patients with metastatic prostate cancer and on single prostate cancer cell line LNCaP cells spiked into the blood of healthy donors.

DNA methylation profiling reveals novel biomarkers and important roles for DNA methyltransferases in prostate cancer.

Candidate gene-based studies have identified a handful of aberrant CpG DNA methylation events in prostate cancer. However, DNA methylation profiles have not been compared on a large scale between prostate tumor and normal prostate, and the mechanisms behind these alterations are unknown. In this study, we quantitatively profiled 95 primary prostate tumors and 86 benign adjacent prostate tissue samples for their DNA methylation levels at 26,333 CpGs representing 14,104 gene promoters by using the Illumina HumanMethylation27 platform.

Nuclear magnetic resonance detects phosphoinositide 3-kinase/Akt-independent traits common to pluripotent murine embryonic stem cells and their malignant counterparts.

Pluripotent embryonic stem (ES) cells, a potential source of somatic precursors for cell therapies, cause tumors after transplantation. Studies of mammalian carcinogenesis using nuclear magnetic resonance (NMR) spectroscopy have revealed changes in the choline region, particularly increased phosphocholine (PCho) content. High PCho levels in murine ES (mES) cells have recently been attributed to cell pluripotency.