Medulloblastoma (MB) is one of the most common pediatric cancers, likely originating from abnormal development of cerebellar progenitor neurons. MicroRNA (miRNA) has been shown to play an important role in the development of the central nervous system. Microarray analysis was used to investigate miRNA expression in desmoplastic MB from patients diagnosed at a young age (1 or 2 years old). Normal fetal or newborn cerebellum was used as control. A total of 84 differentially expressed miRNAs (64 downregulated and 20 upregulated) were found. Most downregulated miRNAs (32/64) were found to belong to the cluster of miRNAs at the 14q32 locus, suggesting that this miRNA locus is regulated as a module in MB. Possible mechanisms of 14q32 miRNAs downregulation were investigated by the analysis of publicly available gene expression data sets. First, expression of estrogen-related receptor-γ (ESRRG), a reported positive transcriptional regulator of some 14q32 miRNAs, was found downregulated in desmoplastic MB. Second, expression of the parentally imprinted gene MEG3 was lower in MB in comparison to normal cerebellum, suggesting a possible epigenetic silencing of the 14q32 locus. miR-129-5p (11p11.2/7q32.1), miR-206 (6p12.2), and miR-323-3p (14q32.2), were chosen for functional studies in DAOY cells. Overexpression of miR-129-5p using mimics decreased DAOY proliferation. No effect was found with miR-206 or miR-323 mimics.

Rare diseases affect up to 13.2 million individuals in Brazil. The Brazilian Rare Genomes Project is envisioned to further the implementation of genomic medicine into the Brazilian public healthcare system. Here we report the validation results of a whole genome sequencing (WGS) procedure for implementation in clinical laboratories. In addition, we report data quality for the first 1,200 real-world patients sequenced. We sequenced a well-characterized group of 76 samples, including seven gold standard genomes, using a PCR-free WGS protocol on Illumina Novaseq 6,000 equipment. We compared the observed variant calls with their expected calls, observing good concordance for single nucleotide variants (SNVs; mean F-measure = 99.82%) and indels (mean F-measure = 99.57%). Copy number variants and structural variants events detection performances were as expected (F-measures 96.6% and 90.3%, respectively). Our WGS protocol presented excellent intra-assay reproducibility (coefficients of variation ranging between 0.03% and 0.20%) and inter-assay reproducibility (coefficients of variation ranging between 0.02% and 0.09%). Limitations of the WGS protocol include the inability to confidently detect variants such as uniparental disomy, balanced translocations, repeat expansion variants, and low-level mosaicism. In summary, the observed performance of the WGS protocol was in accordance with that seen in the best centers worldwide. The Rare Genomes Project is an important initiative to bring pivotal improvements to the quality of life of the affected individuals.

Chimerism is rare in humans and is usually discovered accidentally when a 46,XX and 46,XY karyotype is found in a same individual. We describe a malformed female infant with neural tube defect (NTD) and a 47,XY,+21[5]/46,XX[30] karyotype

Introduction Almost all neoplasms have their prognosis determined by cytogenetic and molecular factors, which determines a tailored approach for each case. According to the World Health Organization, every case of Acute Lymphoblastic Leukemia (ALL) must be classified not only immunophenotypically but also from a genetic point of view. Over the last few years, it has been recognized the differences in incidence and genetic profile of ALL from Latin America (LA). In Brazil, a large country with a distinctive ethnical background when compared to the rest of LA, few reports on ALL have been published and there is a limited availability of genetic tests for classification, especially in public health service. Objective To describe cytogenetic (karyotype and fluorescence in situ hybridization, FISH), molecular markers and World Health Organization (WHO) -2016 classification of diagnostic samples sent to two reference centers in Brazil. Material and Methods This is a cross-sectional study involving patients diagnosed with ALL from January 2014 to May 2018. Diagnostic bone marrow specimens were analyzed by G band conventional karyotyping (Nomenclature according International System for Human Cytogenomic 2016) (n: 157), molecular markers [(genic fusions by RT-PCR - BCR-ABL1 (n: 96), TCF3-PBX1 (n: 77), ETV6-RUNX1 (n: 83), KMT2A-AFF (n:74)] and B-ALL multi-probe FISH (n:54) were employed according to manufacturer's recommendations and following international guidelines. It was attempted to classify all cases by WHO-2016, as well as by age. Samples with no metaphases, non-conclusive or without molecular tests were considered non-classifiable Results Samples from 157 ALL patients at diagnosis were analyzed. Median age was 8 years old (1 month - 88 years) [6 (3.8%) cases had less than 12 months; 99 (63%) between 1 to 15 years; 22 (14%) between 16 and 39 years and 30 (19.1%) older than 40 years]. The majority were B cell lineage ALL (93%). Thirty cases were excluded due to missing immunophenotyping, karyotype and/or molecular studies. Alterations were detected in 94 (74%) of 127 cases [88 (76%)/116 in B-ALL and 6 (54%)/11 in T-ALL. It was possible to classify by WHO 2016 B-ALL subtypes 116 cases, all of them stratified by age groups (Graphic 1). Conclusion Our results are consistent with the literature, showing that KMT2A rearrangement predominates in infant ALL, while a pediatric age range from 1 to 15 years old, with a predominance of good prognostic subtypes: hyperdiploidy and ETV6-RUNX1. In adults, there is predominance of the BCR-ABL1 subtype, which seems to be more frequent than non-Latin cohorts. B-ALL NOS was detected in 27.8% of the cases, predominating in the age group of 16 to 39 years, which may correspond to Ph-like ALL, a recently described subtype linked to a worse prognosis and seemingly more common in latinos. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

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