Anti-PIGH monoclonal antibody Made to order

This study was designed to identify predictive signatures of pathological complete response (pCR) in breast cancer treated by taxane-based regimen, using clinicopathological variables and transcriptomic data (Affymetrix Hgu133 Plus 2.0 devices). The REMAGUS 02 trial (n = 153, training set) and the publicly available M. D. Anderson data set (n = 133, validation set) were used. A re-sampling method was applied. All predictive models were defined using logistic regression and their classification performances were tested through Area Under the Curve (AUC) estimation. A stable set of 42 probesets (31 genes) differentiate pCR or no pCR samples. Single-or 2-probesets signatures, mainly related to ER pathway, were equally predictive of pCR with AUC greater then 0.80. Models including probesets associated with ESR1, MAPT, CA12 or PIGH presented good classification performances. When clinical variables were entered into the model, only CA12 and PIGH, remained informative (p = 0.05 and p = 0.005) showing that a combination of a few genes provided robust and reliable prediction of pCR. (C) 2013 Elsevier Ltd. All rights reserved.

PIGC (OMIM 601730) encodes the PIGC protein, which is part of an enzyme complex involved in the biosynthesis of the glycosylphosphatidylinositol protein anchor. The other proteins in the complex include PIGA, PIGH, PIGQ, PIGY, PIGP and DPM2. Homozygous and compound heterozygous mutations in PIGC have recently been described to cause severe global developmental delay, intellectual disability, and seizures in two unrelated families, without indication of another system involvement or dysmorphism. Here we describe two siblings, born to second cousin parents, displaying severe psychomotor delay, seizures, organomegaly, cardiopulmonary anomalies, and similar facial dysmorphism. Exome sequencing in the boy revealed a homozygous variant in PIGC gene, c.12_13insTTGTGACTAACA leading to a premature stop codon p.(Gln4_Pro5insLeu*). His affected sister was also found to be homozygous, and their parents were found to be heterozygous. This is the first detailed clinical description of two related patients suggesting that PIGC deficiency can cause a severe recognisable phenotype including multisystem disorders, in association to previously reported severe developmental delay and seizures.