Cell-free plasma microRNAs that identify patients with glioblastoma.

Glioblastoma (GBM) is still one of the most commonly diagnosed advanced stage primary brain tumors. Current treatments for patients with primary GBM (pGBM) are often not effective and a significant proportion of the patients with pGBM recur. The effective treatment options for recurrent GBM (rGBM) are limited and survival outcomes are poor. This retrospective multicenter pilot study aims to determine potential cell-free microRNAs (cfmiRs) that identify patients with pGBM and rGBM tumors. 2,083 miRs were assessed using the HTG miRNA whole transcriptome assay (WTA). CfmiRs detection was compared in pre-operative plasma samples from patients with pGBM (n = 32) and rGBM (n = 13) to control plasma samples from normal healthy donors (n = 73). 265 cfmiRs were found differentially expressed in plasma samples from pGBM patients compared to normal healthy donors (FDR < 0.05). Of those 193 miRs were also detected in pGBM tumor tissues (n = 15). Additionally, we found 179 cfmiRs differentially expressed in rGBM, of which 68 cfmiRs were commonly differentially expressed in pGBM. Using Random Forest algorithm, specific cfmiR classifiers were found in the plasma of pGBM, rGBM, and both pGBM and rGBM combined. Two common cfmiR classifiers, miR-3180-3p and miR-5739, were found in all the comparisons. In receiving operating characteristic (ROC) curves analysis for rGBM miR-3180-3p showed a specificity of 87.7% and a sensitivity of 100% (AUC = 98.5%); while miR-5739 had a specificity of 79.5% and sensitivity of 92.3% (AUC = 90.2%). This study demonstrated that plasma samples from pGBM and rGBM patients have specific miR signatures. CfmiR-3180-3p and cfmiR-5739 have potential utility in diagnosing patients with pGBM and rGBM tumors using a minimally invasive blood assay.

A Novel 31.1 kb α-Thalassemia Deletion (- -MEX3) Found in a Mexican Family.

α-Thalassemia (α-thal), a genetic disease characterized by microcytosis, hypochromia and anemia, is predominantly caused by deletions of the α-globin genes, HBA2 and HBA1. In this study, we describe a novel 31.1 kb α-thal deletion, - -MEX3 (NC_000016.10: g.151479_182582del), observed in a Mexican family, probably originated from non homologous recombination between two Alu sequences; the 5' Alu element has been involved in at least two other α-thal deletions [- -FIL (NG_000006.1: g.11684_43534del) and - -KOL] and possesses a core homologous sequence next to the - -MEX3 breakpoint. In addition, a 286 bp insertion in an Alu sequence downstream to the - -MEX3 3' breakpoint was found in the studied family, - -FIL carriers, and healthy subjects, suggesting a common genetic variation in the Mexican population. We highlight the involvement of Alu elements and their core sequence in the origin of deletions in the α-globin gene cluster, and the importance of characterizing rare mutations, to better understand DNA rearrangement origins.