The dawn of the liquid biopsy in the fight against cancer

ABSTRACT Cancer is a molecular disease associated with alterations in the genome, which, thanks to the highly improved sensitivity of mutation detection techniques, can be identified in cell-free DNA (cfDNA) circulating in blood, a method also called liquid biopsy. This is a non-invasive alternative to surgical biopsy and has the potential of revealing the molecular signature of tumors to aid in the individualization of treatments. In this review, we focus on cfDNA analysis, its advantages, and clinical applications employing genomic tools (NGS and dPCR) particularly in the field of oncology, and highlight its valuable contributions to early detection, prognosis, and prediction of treatment response

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Biobanking—Budgets and the Role of Pathology Biobanks in Precision Medicine

Biobanks have become an important component of the routine practice of pathology. At the 2016 meeting of the Association of Pathology Chairs, a series of presentations covered several important aspects of biobanking. An often overlooked aspect of biobanking is the fiscal considerations. A biobank budget must address the costs of consenting, procuring, processing, and preserving high-quality biospecimens. Multiple revenue streams will frequently be necessary to create a sustainable biobank; partnering with other key stakeholders has been shown to be successful at academic institutions which may serve as a model. Biobanking needs to be a deeply science-driven and innovating process so that specimens help transform patient-centered clinical and basic research (ie, fulfill the promise of precision medicine). Pathology’s role must be at the center of the biobanking process. This ensures that optimal research samples are collected while guaranteeing that clinical diagnostics are never impaired. Biobanks will continue to grow as important components in the mission of pathology, especially in the era of precision medicine

Mass spectrometry-based absolute quantification of amyloid proteins in pathology tissue specimens: Merits and limitations.

To clarify the significance of quantitative analyses of amyloid proteins in clinical practice and in research relating to systemic amyloidoses, we applied mass spectrometry-based quantification by isotope-labeled cell-free products (MS-QBIC) to formalin-fixed, paraffin-embedded (FFPE) tissues. The technique was applied to amyloid tissues collected by laser microdissection of Congo red-stained lesions of FFPE specimens. Twelve of 13 amyloid precursor proteins were successfully quantified, including serum amyloid A (SAA), transthyretin (TTR), immunoglobulin kappa light chain (IGK), immunoglobulin lambda light chain (IGL), beta-2-microglobulin (B2M), apolipoprotein (Apo) A1, Apo A4, Apo E, lysozyme, Apo A2, gelsolin, and fibrinogen alpha chain; leukocyte cell-derived chemotaxin-2 was not detected. The quantification of SAA, TTR, IGK, IGL, and B2M confirmed the responsible proteins, even when the immunohistochemical results were not decisive. Considerable amounts of Apo A1, Apo A4, and Apo E were deposited in parallel amounts with the responsible proteins. Quantification of amyloid protein by MS-QBIC is feasible and useful for the classification of and research on systemic amyloidoses

Development of Standard Operating Procedure (SOP) of Micro-computed tomography (micro-CT) in Pathology

BACKGROUNDAND GOAL: Micro-computed tomography (micro-CT) is an emerging technology in the biomedical field and enables us to analyze 3D structures non-destructively and observe these structures in various directions, thus enabling innovation in this area of pathology. However, application of micro-CT for medicine has just started and optimization per purpose has not yet been done. The purpose of this study is to 1) demonstrate the potential utility of micro-CT in pathology; 2) optimize micro-CT imaging technology and develop a standard operating protocol and; 3) investigate whether micro-CT incurs any radiation damage to pathological tissue samples. MATERIAL AND METHODS:The samples of fresh tissue, formalin fixed tissue and formalin fixed paraffin-embedded (FFPE) tissue blocks were scanned using a custom-built Nikon Metrology micro-CT system with a variety of parameters then evaluated with histology correlation in detail. Radiation damage to tissue samples was also evaluated. Through our study, we have established the scanning protocol and workflow for each type of sample. RESULTS:For fresh/fixed tissue, the house made polystyrene foam container was most ideal and the scanning time for fresh tissue was six minutes at as shortest, in which it is possible to detect neoplastic lesions in the tissue. In case of FFPE blocks, 10 -17 hours scanned images