Biomarkers of proliferation, survival, and migration of human breast tumor cells: future perspectives

Despite recent major advance in the understanding of the mechanisms of breast cancer (BC) progression and in the development of novel therapeutic modalities, BC remains the second leading cause of mortality among women. Mortality is almost invariably due to metastasis. The different histological subtypes of BC and molecular maker expression (ER, PR and HER2) have strong prognostic and predictive values but are not enough to prevent that BC patients (BCP) develop a relapse and metastasis. So the aim of this work was the simultaneous evaluation of the expression of biomarkers related to BC progression and metastasis (OPG, TRAIL, TRAIL receptores (R) [R1, R2, R3 y R4], RANKL, RANK (RANKL-R), SDF-1, CXCR-4 (SDF-1-R), IL-6, IL-6-R, MCSF and M-CSF-R in BC cells together with the study of classic prognostic parameters (age, ER, PR, HER2, tumor size and histological grade) in BCP. Regarding the expression of these biomarkers in BC cells, the results are contradictory.Fil: Labovsky, Vivian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Martinez, Leandro Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Calcagno, María. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Davies, Kevin. Hospital Italiano de La Plata; ArgentinaFil: Wenicke, Alejandra. Hospital Italiano; ArgentinaFil: Garcia Rivello, Hernan. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Fernández Vallone, Valeria Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Chasseing, Norma Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaProceedings of the AACR Special Conference on Tumor Invasion and MetastasisPhiladelphiaEstados UnidosAmerican Association for Cancer Researc

Status in Diffuse Large B Cell Lymphoma not otherwise specified: A single center study from Argentina

BackgroundDiffuse large B-cell Lymphoma (DLBCL) is a heterogeneous disease. Based on Hans? algorithm, DLBCL not otherwise specified (NOS) is classified by cell-of-origin into germinal center B-cell (GCB) and non-GCB subtypes. Non-GCB ones have frequently NF-kB pathway activation and worse prognosis compared to GCB cases. MYD88 is an adaptor protein of toll-like and IL-1 receptor signalling, leading downstream NF-kB pathway activation. MYD88 L265P mutation confers the protein constitutional activation. This mutation is present in around 20% of non-GCB subtype, and rarely found in GCB subtype of DLBCL. The prognostic value of MYD88 L265P mutation in DLBCL has been matter of controversy.AimsThe aim of the study was to determine the prevalence of MYD88 L265P mutation in DLBCL NOS cases of Argentina, and compare it with previous reports in the literature.MethodsA retrospective cohort of 73 DLBCL NOS cases diagnosed in the Italian Hospital of Buenos Aires (Argentina) between 2010 and 2016 was studied. Complete clinical records, Hans? algorithm, and available material for molecular testing were inclusion criteria. Patients with prior diagnosis of low-grade lymphoma or diagnosis of immunodeficiency-associated, post-transplant, EBV+, primary mediastinal, primary testicular, primary CNS, primary effusion, leg-type or intravascular DLBCL were excluded. DNA was extracted from tissue blocks using QIAamp mini kit (Qiagen). MYD88 L265P was assessed using an in-house allele-specific probe-based Real-Time PCR assay. Positive (primary testicular DLBCL) and negative controls (tonsil) were added to each run. Every case was checked subsequently using qBiomarker MYD88 L265P Somatic Mutation Assay (Qiagen). Prevalences were expressed as percentage, confident intervals were calculated using Clopper-Pearson exact method. Kaplan Meier curves and Log-rank test were used to evaluate overall survival (OS).Results36 patients (49,31%) were female, and median age at diagnosis was 66 years (range 26-89). 33 patients (45,20%) had extranodal involvement (gastrointestinal tract: 14 cases; liver: 5 cases; bone: 4 cases; other locations: 10 cases). 44 cases (60,27%) were GCB and 29 (39,73%) were non-GCB DLBCLs. MYD88 L265P mutation was present in 2 cases (2,74% ; CI 95%: 0,33-9,55%) among all DLBCLs, including 1 GCB case (2,27% ; CI 95%: 0,06-12,02%) and 1 non-GCB case (3,45% ; CI 95%: 0,09-17.76%). There was no significant association between MYD88 L265P status, Hans´algorithm subtype, sex, age or Ki67 index and OS.ConclusionIn the analyzed population, the prevalence of GCB and non-GCB subtypes among DLBCL NOS cases was similar to international reports, although we did not find significant difference between both groups regarding OS (p=0,712). MYD88 L265P mutation was found only in 2 patients (1 GCB and 1 non-GCB), accounting for 2,74% (CI 95%: 0,33-9,55%) and 2,27% (CI 95%: 0,06-12,02%) of all DLBCL NOS and non-GCB cases, respectively. Both prevalences are significantly lower than those published in 2017 by Lee et al. in a meta-analysis, where they found that MYD88 L265P is present in 16% (CI 95%: 15-18,09%) and 20,63% (CI 95%: 18,41-23%) of patients among all DLBCLs and non-GCB subtype, respectively. However, MYD88 L265P prevalence in primary SNC, testicular and leg-type DLBCLs diagnosed in our institution are similar to the literature (data not shown).Fil: Jauk, Federico. Hospital Italiano; ArgentinaFil: Kohan, Dana. Hospital Italiano; ArgentinaFil: Ortega, Leandro Ismael. Hospital Italiano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Diaz de Arce, Heidy. Hospital Italiano; ArgentinaFil: Cristaldo, Nancy. Hospital Italiano; ArgentinaFil: RANUNCOLO, Stella Maris. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; ArgentinaFil: Warley, Fernando. Hospital Italiano; ArgentinaFil: Otero, Victoria. Hospital Italiano; ArgentinaFil: Garcia Rivello, Hernan Jorge. Hospital Italiano; Argentina24th Congress of the European Hematology AssociationAmsterdamHolandaEscuela Europea de Hematologí

Global DNA Methylation levels analysis in a serie of Hematological, Breast and Colorectal cancer samples from Argentina

Unlike their normal counterparts, tumor cells exhibited highly variable CpG methylation levels in a large proportion of the genome, which can lead to malignant cell transformation through multiple pathways. This prompted us to assess the extent of LINE1 methylation, a surrogate marker of global DNA methylation, of samples derived from controls and cancer patients from Argentina. Preliminary DNA methylation results from selected samples were replicated in a large serie of 146 controls (blood) and various cancer types: 112 oncohematological cancer (HemCa), 70 colorectal cancer (CRC) and 68 breast cancer (BrCa) samples. Further, we evaluated correlation with biological, clinical and demographic features. Blood samples were available in all cases, and for solid tumors paired tumoral/non-tumoral adjacent tissues (T/N) were available too. LINE1 methylation level was analyzed by MS-MLPA method. HemCa cases showed statistically significant higher LINE1 methylation level (p>0.001) compared to controls (mean 0.93 and 0.84, respectively). This variation could be a consequence of chemotherapy. Methylation status in blood (0.86) and N tissue (0.87) from BrCa cases did not differ from controls, while levels in T tissue (0.88) were significantly higher than controls (p<0.05). No differences between N and T tissues were found. CRC cases showed hypomethylation for LINE1 when comparing T (0.81) to blood (0.87) or N tissues (0.88), reaching statistical significance of p<0.05 and p<0.001, respectively. This is in line with reported results. We found a negative correlation between individual age and methylation level in controls (-0.17, p=0.04), and BrCa T tissue (-0.33, p=0.03). Finally, no relevant associations between global methylation and mitochondrial genome variation (copy number and ancestry) were found for controls and HemCa sample sets. LINE1 methylation analysis in samples from lung, ovarian, pancreatic and skin cancers are ongoing.Fil: Cerliani, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Mayordomo, Andrea Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Sanchez Dova, Anaclara. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Piñero, Tamara Alejandra. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; ArgentinaFil: Cajal, Andrea. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; ArgentinaFil: Jauk Vitali, Federico. Hospital Italiano; ArgentinaFil: Garcia Rivello, Hernan Jorge. Hospital Italiano; ArgentinaFil: Vaccaro, Carlos Alberto. Hospital Italiano; ArgentinaFil: Richard, Silvina Mariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Bravi, Claudio Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Pavicic, Walter Hernan. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; ArgentinaReunión Anual de Sociedades de BiocienciaArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de Farmacología ExperimentalSociedad Argentina de BiologíaSociedad Argentina de BiologíaAsociación Argentina de NanomedicinasAsociación Argentina de Ciencia y Tecnología de Animales de Laboratori

CD105 expression in cancer-associated fibroblasts: a biomarker for bone metastasis in early invasive ductal breast cancer patients

Introduction: Bone metastasis is one of the causes that mainly decrease survival in patients with advanced breast cancer. Therefore, it is essential to find prognostic markers for the occurrence of this type of metastasis during the early stage of the disease. Currently, cancer-associated fibroblasts, which represent 80% of the fibroblasts present in the tumor microenvironment, are an interesting target for studying new biomarkers and developing alternative therapies. This study evaluated the prognostic significance of the CD105 expression in cancer-associated fibroblasts in early breast cancer patients. Methods: Immunohistochemistry was used to assess CD105 expression in invasive ductal breast carcinomas (n = 342), analyzing its association with clinical and pathological characteristics. Results: High CD105 expression in cancer-associated fibroblasts was associated with an increased risk of metastatic occurrence (p = 0.0003), particularly bone metastasis (p = 0.0005). Furthermore, high CD105 expression was associated with shorter metastasis-free survival, bone metastasis-free survival, and overall survival (p = 0.0002, 0.0006, and 0.0002, respectively). CD105 expression also constituted an independent prognostic factor for metastasis-free survival, bone metastasis-free survival, and overall survival (p = 0.0003, 0.0006, and 0.0001, respectively). Discussion: The high CD105 expression in cancer-associated fibroblasts is an independent prognostic marker for bone metastasis in early breast cancer patients. Therefore, the evaluation of CD105(+) CAFs could be crucial to stratify BCPs based on their individual risk profile for the development of BM, enhancing treatment strategies and outcomes.Fil: Giorello, Maria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Martinez, Leandro Marcelo. Cornell University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Borzone, Francisco Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Padin, María del Rosario. Hospital Italiano; ArgentinaFil: Mora, María Florencia. Hospital Italiano; ArgentinaFil: Sevic, Ina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; ArgentinaFil: Alaniz, Laura Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; ArgentinaFil: Calcagno, María de Luján. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Garcia Rivello, Hernan Jorge. Hospital Italiano; ArgentinaFil: Wernicke, Alejandra. Hospital Italiano; ArgentinaFil: Labovsky, Vivian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Chasseing, Norma Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

Mono- and biallelic germline variants of DNA glycosylase genes in colon adenomatous polyposis families from two continents

Recently, biallelic germline variants of the DNA glycosylase genes MUTYH and NTHL1 were linked to polyposis susceptibility. Significant fractions remain without a molecular explanation, warranting searches for underlying causes. We used exome sequencing to investigate clinically well-defined adenomatous polyposis cases and families from Finland (N=34), Chile (N=21), and Argentina (N=12), all with known susceptibility genes excluded. Nine index cases (13%) revealed germline variants with proven or possible pathogenicity in the DNA glycosylase genes, involving NEIL1 (mono- or biallelic) in 3 cases, MUTYH (monoallelic) in 3 cases, NTHL1 (biallelic) in 1 case, and OGG1 (monoallelic) in 2 cases. NTHL1 was affected with the well-established, pathogenic c.268C>T, p.(Gln90Ter) variant. A recurrent heterozygous NEIL1 c.506G>A, p.(Gly169Asp) variant was observed in two families. In a Finnish family, the variant occurred in trans with a truncating NEIL1 variant (c.821delT). In an Argentine family, the variant co-occurred with a genomic deletion of exons 2 - 11 of PMS2. Mutational signatures in tumor tissues complied with biological functions reported for NEIL1. Our results suggest that germline variants in DNA glycosylase genes may occur in a non-negligible proportion of unexplained colon polyposis cases and may predispose to tumor development.Peer reviewe

Prognostic impact of bone marrow fibrosis in primary myelodysplastic syndromes

La mielofibrosis (MF) se observa en el 10-20% de los pacientes con síndrome mielodisplásico (SMD). Su presencia es reconocida como un hallazgo histológico adverso asociado a curso agresivo, fallo medular temprano, sobrevida acortada y evolución leucémica.El objetivo fue examinar la influencia de la MF (MF ≥1) en la sobrevida global (SG) y su asociacióncon variables clínicas e histopatológicas.Se identificaron 468 pacientes con SMD incluidos en el Registro Argentino de SMD de 2007 a 2017.La mediana de SG del subgrupo MF ≥1 fue de 20,1 meses (IC 95%: 10,1-30,0) versus 67,6 meses (IC95% 45,1-90,3) del subgrupo MF-0 (p2 (HR 2,07, 95% IC 1,44-2,96; p5% (HR 2,94,IC 95% 2,06-4,20; p3 (HR 2,17; IC 95%: 1,48-3,19;p1000 ug/L (OR 3,41; p= 0,006) y la localización eritroide atípica (OR 2,65; p=0,004) se asociaron significativamente con la presencia de MF ≥1.Los resultados destacan la presencia de MF ≥1 como un factor pronóstico adverso para la supervivencia en SMD, asociado con hiperferritinemia y alteración de la localización de la progenie eritroide en la MO.Myelofibrosis (MF) is observed in 10-20% of patients with myelodysplastic syndrome (MDS). The presence of MF has been recognized as an adverse histological finding associated with an aggressive course including early bone marrow (BM) failure, shortened survival and leukemic evolution. The aim of this study was to examine the influence of the myelofibrosis (MF ≥1) in the overall survival (OS) and its association with clinical and histopathologic variables. We identified 468 MDS patients who were included in the Argentinian Registry of MDS from 2007 to 2017. The median OS for the MF≥1 subgroup was 20.1 months (95% CI 10.1-30.0) versus 67.6 months (95% CI 45.1-90.3) for the MF-0 subgroup (p2 (HR 2.07, 95% CI 1.44-2.96; p5% (HR 2.94, 95% CI 2.06-4.20; p3 (HR 2.17, 95% CI 1.48- 3.19; p 1000 ug/L (OR 3.41; p=0.006) and the atypical erythroid localization (OR 2.65; p=0.004) were significantly associated with the presence of MF ≥1. Our results highlight the presence of any grade of myelofibrosis as an independent adverse prognostic factor for survival in MDS, associated with higher ferritin level and abnormal erythroid localization in the BM.Fil: Russo, Maria Florencia. Gobierno de la Provincia de Buenos Aires. Hospital Interzonal General de Agudos Paroissien (higa Paroissien); ArgentinaFil: Belli, Carolina Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Enrico, Alicia. Hospital Italiano de La Plata; ArgentinaFil: Arbelbide, Jorge. Hospital Italiano; ArgentinaFil: Narbaitz, Marina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: de Dios Soler, Marcela. Hospital Municipal de Oncologia Maria Curie ; Gobierno de la Ciudad Autonoma de Buenos Aires;Fil: Garcia Rivello, Hernan Jorge. Hospital Italiano; ArgentinaFil: Martin, Carlos. Hospital Italiano de La Plata; ArgentinaFil: Iastrebner, Marcelo. Sanatorio Sagrado Corazón; ArgentinaFil: Gonzalez, Jacqueline. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Carlos Durand; ArgentinaFil: Rosenhain, Mariana. Hospital General de Agudos Dr. Enrique Tornú; ArgentinaFil: Alfonso, Graciela. Hospital Nacional Profesor Alejandro Posadas; ArgentinaFil: Kornblihtt, Laura Inés. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Perusini, Agustina. Hospital Italiano; ArgentinaFil: Lazzarino, Carolina. Gobierno de la Provincia de Buenos Aires. Hospital Interzonal General de Agudos Paroissien (higa Paroissien); Argentin

The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group

The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC

High frequency of WNT-activated medulloblastomas with CTNNB1 wild type suggests a higher proportion of hereditary cases in a Latin-Iberian population

PurposeMedulloblastomas are the most common primary malignant brain tumors in children. They are divided into molecular subgroups: WNT-activated, SHH-Activated, TP53 mutant or wild type, and non-WNT/non-SHH (Groups 3 and 4). WNT-activated medulloblastomas are usually caused by mutations in the CTNNB1 gene (85%–90%), and most remaining cases of CTNNB1 wild type are thought to be caused by germline mutations in APC. So far, the frequencies of CTNNB1 have been reported mainly in North American and European populations. The aim of this study was to report the frequency of CTNNB1 mutations in WNT-activated medulloblastomas in a Latin-Iberian population and correlate with their clinicopathological characteristics.MethodsA total of 266 medulloblastomas from seven different institutions from Brazil (n=211), Portugal (n=38), and Argentina (n=17) were evaluated. Following RNA and DNA isolation from formalin-fixed, paraffin-embedded (FFPE) tumor tissues, the molecular classification and CTNNB1 mutation analysis were performed by nCounter and Sanger sequencing, respectively.ResultsWNT-activated medulloblastomas accounted for 15% (40/266) of the series. We observed that 73% of WNT-activated medulloblastomas harbored CTNNB1 mutations. CTNNB1 wild-type cases (27%) were more prevalent in female individuals and suggested to be associated with a worse outcome. Among the CTNNB1 wild-type cases, the available analysis of family history revealed two cases with familiar adenomatous polyposis, harboring APC germline variants.ConclusionWe observed a lower incidence of CTNNB1 mutations in WNT-activated medulloblastomas in our Latin-Iberian cohort compared to frequencies previously described in other populations. Considering that CTNNB1 wild-type cases may exhibit APC germline mutations, our study suggests a higher incidence (~30%) of hereditary WNT-activated medulloblastomas in the Latin-Iberian population

Evidence for an nc(1S)ff- resonance in B0 yc(1S)K+ decays

A Dalitz plot analysis of B0→ηc(1S)K+π- decays is performed using data samples of pp collisions collected with the LHCb detector at centre-of-mass energies of s=7,8 and 13TeV , corresponding to a total integrated luminosity of 4.7fb-1 . A satisfactory description of the data is obtained when including a contribution representing an exotic ηc(1S)π- resonant state. The significance of this exotic resonance is more than three standard deviations, while its mass and width are 4096±20-22+18MeV and 152±58-35+60MeV , respectively. The spin-parity assignments JP=0+ and JP=1- are both consistent with the data. In addition, the first measurement of the B0→ηc(1S)K+π- branching fraction is performed and gives B(B0→ηc(1S)K+π-)=(5.73±0.24±0.13±0.66)×10-4, where the first uncertainty is statistical, the second systematic, and the third is due to limited knowledge of external branching fractions