Mar Mallo - Academia.edu (original) (raw)

Papers by Mar Mallo

IHC protein expression of IDH1, EGFR (intensity 3 as high versus 0-2), high intensity, PTEN, OLIG... more IHC protein expression of IDH1, EGFR (intensity 3 as high versus 0-2), high intensity, PTEN, OLIG2, Ki67 and SOX2 by IGS (first row) and TCGA subtype (second row: KNN, third row: SVM, fourth row: ssGSEA). Significant differences were seen between mesenchymal and classical or proneural tumors. See Supplementary Data File S1e for results simplified in Table 1.

Statistically significant adjusted P-values for differential expression of genes in the pairwise ... more Statistically significant adjusted P-values for differential expression of genes in the pairwise comparison of molecular subtypes. Two of these genes were selected for immunohistochemical analysis for the identification of the mesenchymal subtype.

Representative images comparing high versus low immunohistochemical expression of (A,B) EGFR,(C,D... more Representative images comparing high versus low immunohistochemical expression of (A,B) EGFR,(C,D) PTEN, (E,F) SOX-2, (G,H) SHC1, (I,J) TCIRG1,(K,L) IDH1R132H (K:positive, L: negative), (M,N) Olig2,and (O,P) Ki67

Purpose:Molecular subtype classifications in glioblastoma may detect therapy sensitivities. IHC w... more Purpose:Molecular subtype classifications in glioblastoma may detect therapy sensitivities. IHC would potentially allow the identification of molecular subtypes in routine clinical practice.Experimental Design:Formalin-fixed, paraffin-embedded tumor samples of 124 uniformly treated, newly diagnosed patients with glioblastoma were submitted to RNA sequencing, IHC, and immune-phenotyping to identify differences in molecular subtypes associated with treatment sensitivities.Results:We detected high molecular and IHC overlapping of the The Cancer Genome Atlas (TCGA) mesenchymal subtype with instrinsic glioma subtypes (IGS) cluster 23 and of the TCGA classical subtype with IGS cluster 18. IHC patterns, gene fusion profiles, and immune-phenotypes varied across subtypes. IHC revealed that the TCGA classical subtype was identified by high expression of EGFR and low expression of PTEN, while the mesenchymal subtype was identified by low expression of SOX2 and high expression of two antibodies...

Spearman correlation between gene and protein expression for the four antibodies selected accordi... more Spearman correlation between gene and protein expression for the four antibodies selected according to RNA-Seq differential expression.

Clinical Lymphoma Myeloma and Leukemia

Scientific Reports

RNA-Sequencing (RNA-Seq) can identify gene fusions in tumors, but not all these fusions have func... more RNA-Sequencing (RNA-Seq) can identify gene fusions in tumors, but not all these fusions have functional consequences. Using multiple data bases, we have performed an in silico analysis of fusions detected by RNA-Seq in tumor samples from 139 newly diagnosed glioblastoma patients to identify in-frame fusions with predictable oncogenic potential. Among 61 samples with fusions, there were 103 different fusions, involving 167 different genes, including 20 known oncogenes or tumor suppressor genes (TSGs), 16 associated with cancer but not oncogenes or TSGs, and 32 not associated with cancer but previously shown to be involved in fusions in gliomas. After selecting in-frame fusions able to produce a protein product and running Oncofuse, we identified 30 fusions with predictable oncogenic potential and classified them into four non-overlapping categories: six previously described in cancer; six involving an oncogene or TSG; four predicted by Oncofuse to have oncogenic potential; and 14 oth...

Blood

Cytogenetics has long represented a critical component in the clinical evaluation of hematologic ... more Cytogenetics has long represented a critical component in the clinical evaluation of hematologic malignancies. Chromosome banding studies provide a simultaneous snapshot of genome-wide copy number and structural variation, which have been shown to drive tumorigenesis, define diseases, and guide treatment. Technological innovations in sequencing have ushered in our present-day clinical genomics era. With recent publications highlighting novel sequencing technologies as alternatives to conventional cytogenetic approaches, we, an international consortium of laboratory geneticists, pathologists, and oncologists, describe herein the advantages and limitations of both conventional chromosome banding and novel sequencing technologies and share our considerations on crucial next steps to implement these novel technologies in the global clinical setting for a more accurate cytogenetic evaluation, which may provide improved diagnosis and treatment management. Considering the clinical, logisti...

Blood, 2021

The prevailing theory in del(5q) is that haploinsuffciency (HI) stemming from deletion and not si... more The prevailing theory in del(5q) is that haploinsuffciency (HI) stemming from deletion and not simply LOH (loss of heterozygosity) is the culprit in clonal evolution. To date no haploinsufficient gene has been found to be the leukemogenic factor conveying growth advantage, but various other genes have been found to be important for phenotypic features or for propensity to acquire subsequent specific lesions. RPS14 is an example of such a gene, particularly in patients (pts) with isolated del(5q), responsible for macrocytic anemia and erythroid dysplasia and a propensity for acquisition of TP53 mutations. We hypothesized that RPS14 downmodulation and its consequences may be more common than del(5q) and it is frequent pathophysiologic feature in MDS. We first analyzed the genomic and expression profile of 170 pts with del(5q) and 825 diploid for 5q. We developed a new analytic pipeline to identify the most HI genes present in a large number of del(5q) pts. Genes within CDR (common del...

Cancers, 2021

Myelodysplastic syndromes (MDS) are a heterogeneous group of hematological diseases. Among them, ... more Myelodysplastic syndromes (MDS) are a heterogeneous group of hematological diseases. Among them, the most well characterized subtype is MDS with isolated chromosome 5q deletion (MDS del(5q)), which is the only one defined by a cytogenetic abnormality that makes these patients candidates to be treated with lenalidomide. During the last decade, single cell (SC) analysis has emerged as a powerful tool to decipher clonal architecture and to further understand cancer and other diseases at higher resolution level compared to bulk sequencing techniques. In this study, a SC approach was used to analyze intratumoral heterogeneity in four patients with MDS del(5q). Single CD34+CD117+CD45+CD19- bone marrow hematopoietic stem progenitor cells were isolated using the C1 system (Fluidigm) from diagnosis or before receiving any treatment and from available follow-up samples. Selected somatic alterations were further analyzed in SC by high-throughput qPCR (Biomark HD, Fluidigm) using specific TaqMa...

Scientific Reports, 2021

Haematopoietic malignancies are frequently characterized by karyotypic abnormalities. The develop... more Haematopoietic malignancies are frequently characterized by karyotypic abnormalities. The development of targeted drugs has been pioneered with compounds against gene products of fusion genes caused by chromosomal translocations. While polysomies are equally frequent as translocations, for many of them we are lacking therapeutic approaches aimed at synthetic lethality. Here, we report two new cell lines, named MBU-7 and MBU-8, that differ in complete trisomy of chromosome18, a partial trisomy of chromosome 7 and a tetrasomy of the p-arm of chromosome 8, but otherwise share the same mutational pattern and complex karyotype. Both cell lines are divergent clones of U-937 cells and have the morphology and immunoprofile of monocytic cells. The distinct karyotypic differences between MBU-7 and MBU-8 are associated with a difference in the specific response to nucleoside analogues. Taken together, we propose the MBU-7 and MBU-8 cell lines described here as suitable in vitro models for scre...

Blood, 2014

INTRODUCTION AND AIMS: Abnormalities of chromosome 1 (chr 1) are frequently found in hematopoieti... more INTRODUCTION AND AIMS: Abnormalities of chromosome 1 (chr 1) are frequently found in hematopoietic stem cell disorders, but their impact and prognosis in Myelodysplastic Syndrome (MDS) remains unclear. For this reason, we retrospectively analyzed a large series of patients. MATERIALS AND METHODS: A series of 90 patients with MDS and abnormalities of chr 1 were retrospectively evaluated, coming from the Spanish Registry of MDS (68), Marqués de Valdecilla Universitary Hospital (16) and Azienda Careggi Universitary Hospital (Florence) (6). We compared this group to a control group of 992 patients with MDS and an abnormal karyotype, but without abnormalities of chr 1, included in the Spanish Registry of MDS. RESULTS: Abnormalities of chr 1 occurred in 8.3% of patients with MDS. Fifty seven percent belonged to the high/very high IPSS-R (Revised International Prognostic Scoring System) risk group. The median number of chromosomal abnormalities in the group with and without chr 1 involveme...

Blood, 2010

4008 Introduction: Loss of the Y chromosome has been reported to be associated with hematopoietic... more 4008 Introduction: Loss of the Y chromosome has been reported to be associated with hematopoietic diseases (Wiktor et al., 2000), but it was also described as an age-related phenomenon in males (UKCCG, 1992). Determination of clonality and prediction of prognosis and treatment outcome might benefit from a differentiation between age- and MDS-associated Y loss. The aim of this study was to evaluate if Y loss was an age- and/or MDS-associated phenomenon by retrospectively analyzing our multicenter, international DACH-, ICWG- and IMRAW-database and by testing the established hypotheses in an experimental study. Patients and Methods: In our multicenter MDS-database of 2901 patients, 101 primary, untreated MDS patients (3.5%) with loss of the Y were identified. We analyzed them according to age, clone size, and the presence or absence of additional chromosomal aberrations and assessed the prognostic relevance of the aberrations using univariate and multivariate models. Additionally, by i...

Blood, 2009

2772 Poster Board II-748 Introduction: The IPSS-Score, published by Greenberg et al. (1997), defi... more 2772 Poster Board II-748 Introduction: The IPSS-Score, published by Greenberg et al. (1997), defines the gold standard in risk stratification of patients with MDS. Since its implementation in 1997 based on 816 patients with primary MDS, the knowledge concerning the prognostic impact of distinct abnormalities increased extensively. The present study proposes a new and comprehensive cytogenetic scoring system based on an international data collection of 3803 patients, originating from the German-Austrian (GA)-, the International Risk analysis workshop (IMRAW)- and the Spanish Cytogenetics working group (GCECGH). Additionally, 53 cases of rare abnormalities were contributed by the International Cytogenetics Working Group of the MDS Foundation (ICWG), resulting in total number of 3856 pts. As compared to our previous reports, the data set was substantially enlarged by adding the GCECGH cases and data quality was improved by updating the clinical and survival data; allowing the analysis ...

Blood, 2016

Background: Whole genome amplification (WGA) has become an invaluable method for working with sma... more Background: Whole genome amplification (WGA) has become an invaluable method for working with small amounts of starting DNA and for preserving limited samples of precious stock material. Next-Generation Sequencing (NGS) techniques can benefit from WGA, but due to their high sensitivity, WGA reliability needs to be certified to ensure an unbiased and accurate amplification of whole genomes. Myelodysplastic Syndromes (MDS) are a group of clonal hematopoietic stem cell disorders characterized by presenting somatic mutations in several myeloid-related genes. We have performed whole exome sequencing (WES) and targeted deep sequencing in tumoral samples from MDS patients. With the aim to determine if Multiple Displacement Amplification-based WGA can be applied to perform NGS in these type of samples and to obtain valuable results, targeted deep sequencing was performed on both fresh-DNA and WGA-DNA from the same patients. Mehtods: Whole bone marrow samples from four MDS patients were incl...