Novel high-risk acute myeloid leukemia subgroup with ERG amplification and Biallelic loss of TP53.

ETS-related gene (ERG) amplification, observed in 4-6% of acute myeloid leukemia (AML), is associated with unfavorable prognosis. To determine coincident effects of additional genomic abnormalities in AML with ERG amplification (ERGamp), we examined 11 ERGamp cases of 205 newly diagnosed AML using chromosomal microarray analysis and next generation sequencing. ERGamp cases demonstrated a distinct pattern of high genetic complexity: loss of 5q, chromothripsis and TP53 loss of function variants.

Clinical utility of chromosomal microarray in establishing clonality and high risk features in patients with Richter transformation.

Richter transformation (RT) refers to the development of an aggressive lymphoma in patients with pre-existing chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). It carries a poor prognosis secondary to poor response to therapy or rapid disease relapse. Currently there are no randomized trials to guide treatment.

Establishment and genomic characterization of a sporadic malignant peripheral nerve sheath tumor cell line.

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive Schwann cell-derived neoplasms that occur sporadically or in patients with neurofibromatosis type 1 (NF1). Preclinical research on sporadic MPNSTs has been limited as few cell lines exist. We generated and characterized a new sporadic MPNST cell line, 2XSB, which shares the molecular and genomic features of the parent tumor.

Near haploidization is a genomic hallmark which defines a molecular subgroup of giant cell glioblastoma.

Background: Giant cell glioblastoma (gcGBM) is a rare histologic subtype of glioblastoma characterized by numerous bizarre multinucleate giant cells and increased reticulin deposition. Compared with conventional isocitrate dehydrogenase (IDH)-wildtype glioblastomas, gcGBMs typically occur in younger patients and are generally associated with an improved prognosis. Although prior studies of gcGBMs have shown enrichment of genetic events, such as alterations, no defining aberrations have been identified.

Integrated genomic analysis using chromosomal microarray, fluorescence in situ hybridization and mate pair analyses: Characterization of a cryptic t(9;22)(p24.1;q11.2)/BCR-JAK2 in myeloid/lymphoid neoplasm with eosinophilia.

The 2016 World Health Organization entity 'Myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB or FGFR1, or with PCM1-JAK2' encompasses a group of rare neoplasms that result from the formation of a fusion gene that leads to expression of an aberrant tyrosine kinase. This entity also contains variant JAK2 fusion partners, and detection of this defining event can be facilitated by various cytogenetic and molecular methods. Cryptic rearrangements of 9p24/JAK2 can be particularly challenging to identify.

Cryptic and atypical KMT2A-USP2 and KMT2A-USP8 rearrangements identified by mate pair sequencing in infant and childhood leukemia.

Infant leukemias are a rare group of neoplasms that are clinically and biologically distinct from their pediatric and adult counterparts. Unlike leukemia in older children where survival rates are generally favorable, infants with leukemia have a 5-year event-free survival rate of <50%. The majority of infant leukemias are characterized by KMT2A (MLL) rearrangements (~70 to 80% in acute lymphoblastic leukemia), which appear to be drivers of early leukemogenesis.

A high prevalence of biallelic RPE65 mutations in Costa Rican children with Leber congenital amaurosis and early-onset retinal dystrophy.

Background: Leber congenital amaurosis (LCA) and early-onset retinal dystrophy (EORD), are primary causes of inherited childhood blindness. Both are autosomal recessive diseases, with mutations in more than 25 genes explaining approximately ~70% of cases. However, the genetic cause for many cases remains unclear.

Whole-Genome Single Nucleotide Polymorphism Microarray for Copy Number and Loss of Heterozygosity Analysis in Tumors.

The basis of cancer biology is built upon two fundamental processes that result in uncontrolled cell proliferation and tumor formation: loss of tumor suppressor gene function and gain of oncogene function. Somatic DNA copy number variants (CNVs), which generally range in size from kilobases to entire chromosomes, facilitate gains and losses of chromosomal material incorporating oncogenes and tumor suppressor genes, respectively. In fact, many cancer types are characterized by DNA copy number changes and relatively few single nucleotide mutations (Ciriello et al.

Expression of renal cell markers and detection of 3p loss links endolymphatic sac tumor to renal cell carcinoma and warrants careful evaluation to avoid diagnostic pitfalls.

Endolymphatic sac tumor (ELST) is a rare neoplasm arising in the temporal petrous region thought to originate from endolymphatic sac epithelium. It may arise sporadically or in association with Von-Hippel-Lindau syndrome (VHL). The ELST prevalence in VHL ranges from 3 to 16% and may be the initial presentation of the disease.

First Report of Prenatal Ascertainment of a Fetus With Homozygous Loss of the SOX10 Gene and Phenotypic Correlation by Autopsy Examination.

The SOX10 gene plays a vital role in neural crest cell development and migration. Abnormalities in SOX10 are associated with Waardenburg syndrome Types II and IV, and these patients have recognizable clinical features. This case report highlights the first ever reported homozygous loss of function of the SOX10 gene in a human.

A multicenter, cross-platform clinical validation study of cancer cytogenomic arrays.

Cytogenomic microarray analysis (CMA) offers high resolution, genome-wide copy number information and is widely used in clinical laboratories for diagnosis of constitutional abnormalities. The Cancer Genomics Consortium (CGC) conducted a multiplatform, multicenter clinical validation project to compare the reliability and inter- and intralaboratory reproducibility of this technology for clinical oncology applications. Four specimen types were processed on three different microarray platforms-from Affymetrix, Agilent, and Illumina.

Clonal diversity analysis using SNP microarray: a new prognostic tool for chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease. The methods currently used for monitoring CLL and determining conditions for treatment are limited in their ability to predict disease progression, patient survival, and response to therapy. Although clonal diversity and the acquisition of new chromosomal abnormalities during the disease course (clonal evolution) have been associated with disease progression, their prognostic potential has been underappreciated because cytogenetic and fluorescence in situ hybridization (FISH) studies have a restricted ability to detect genomic abnormalities and clonal evolution.

Tetraploidy and 5q deletion in myelodysplastic syndrome: a case report.

Tetraploidy is a very rare cytogenetic abnormality in myelocytic malignancies, and its significance is unclear to date. We report here on a 68-year-old male diagnosed with myelodysplastic syndrome/refractory anemia with excess blasts (MDS/RAEB). Cytogenetic analysis of his bone marrow biopsy at initial clinical presentation and in subsequent studies revealed the presence of two abnormal clones, 92,XXYY and 92,XXYY,del(5)(q13q33).

Collagen binding alpha2beta1 and alpha1beta1 integrins play contrasting roles in regulation of Ets-1 expression in human liver myofibroblasts.

Activation of hepatic stellate cells from quiescence to myofibroblast-like cells (MFBs) is a pivotal event in hepatic fibrogenesis. Plastic-cultured stellate cells (an established in vitro model of the activated phenotype) recultured on Matrigel revert to quiescence. In the present study we analyzed the molecular mechanism underlying this process, focusing on the effect of collagen receptors alpha(2)beta(1) and alpha(1)beta(1) integrin signaling on the expression of Ets-1 transcription factor and its target gene MMP1 in cultured human MFBs.

Expression of oncostatin M and its receptors in normal and cirrhotic human liver.

Background/aims: In the cirrhotic liver, gene expression of the multifunctional cytokine oncostatin M (OSM) is up-regulated, but its cellular origin is unknown. Therefore, we investigated the expression of OSM protein and its specific receptor subunits, OSMRbeta and LIFRbeta in normal and cirrhotic human liver using immunohistochemical and Western blot analysis.

Results: OSM protein was expressed in Kupffer cells, variably in normal liver but consistently in cirrhosis.

Comparative studies of oncostatin M expression in the tissues of adult rodents.

Oncostatin M (OSM), a member of the interleukin-6 family of cytokines, is thought to be expressed mostly by activated T-lymphocytes and monocytes in adult animals. However, here we report specific constitutive tissue expression of OSM in the pancreas, kidney, testes, spleen, stomach, and brain, but not liver or lung, of three adult rodent species.

Reversal of activation of human myofibroblast-like cells by culture on a basement membrane-like substrate.

Background: Liver injury transforms hepatic stellate cells into myofibroblast (MFB)-like cells. With recovery from injury, MFBs undergo apoptosis, but it is unknown whether they can also revert to quiescence.

Aim: To determine whether human (h)MFBs become quiescent if cultured on a basement membrane-like substrate (Matrigel).