Detection of a GLIS3 fusion in an infant with AML refractory to chemotherapy.

Infants diagnosed with acute myeloid leukemia (AML) frequently harbor cytogenetically cryptic fusions involving KMT2A, NUP98 or GLIS2. Those with AML driven specifically by CBFA2T3::GLIS2 fusions have a dismal prognosis and are currently risk-stratified to receive hematopoietic stem cell transplantation (HSCT) in first remission. Here we report an infant with AML who was refractory to multiple lines of chemotherapy but lacked an identifiable fusion despite cytogenetic, fluorescence in situ hybridization (FISH) and targeted next generation sequencing (NGS) testing.

Tumor and Constitutional Sequencing for Neurofibromatosis Type 1.

Purpose: variants in tumors are important to recognize, as multiple mechanisms may give rise to biallelic variants. Both deletions and copy-neutral loss of heterozygosity (LOH) are potential mechanisms of loss, distinct from point mutations, and additional genes altered may drive different tumor types. This study investigates whether tumors from individuals with neurofibromatosis type 1 (NF1) demonstrate additional gene variants and detects second hits using paired germline and somatic sequencing.

CXCL14 Promotes a Robust Brain Tumor-Associated Immune Response in Glioma.

Purpose: The immunosuppressive tumor microenvironment present in the majority of diffuse glioma limits therapeutic response to immunotherapy. As the determinants of the glioma-associated immune response are relatively poorly understood, the study of glioma with more robust tumor-associated immune responses may be particularly useful to identify novel immunomodulatory factors that can promote T-cell effector function in glioma.

Experimental Design: We used multiplex immune-profiling, proteomic profiling, and gene expression analysis to define the tumor-associated immune response in two molecular subtypes of glioma and identify factors that may modulate this response.

Prospective Validation of Molecular Prognostic Markers in Cutaneous Melanoma: A Correlative Analysis of E1690.

To validate the prognostic impact of combined expression levels of three markers (SPP1, RGS1, and NCOA3) in melanoma specimens from patients enrolled in the E1690 clinical trial of high-dose or low-dose IFNα-2b versus observation. Tissue was available from 248 patients. Marker expression was determined by digital imaging of immunohistochemically stained slides.

A Unique Case of Bilateral Hürthle Cell Adenoma in an Adolescent.

Background: Hürthle cell (HC) neoplasms are rare among pediatric thyroid cancers. HC adenomas (HCA) are typically benign and localized unilaterally without recurrence, and they are thus treated by hemithyroidectomy. HC carcinomas (HCC) can be bilateral and are more aggressive, necessitating total thyroidectomy.

The role of BPTF in melanoma progression and in response to BRAF-targeted therapy.

Background: Bromodomain PHD finger transcription factor (BPTF) plays an important role in chromatin remodeling, but its functional role in tumor progression is incompletely understood. Here we explore the oncogenic effects of BPTF in melanoma.

Methods: The consequences of differential expression of BPTF were explored using shRNA-mediated knockdown in several melanoma cell lines.

Prognostic impact of PHIP copy number in melanoma: linkage to ulceration.

Ulceration is an important prognostic factor in melanoma whose biologic basis is poorly understood. Here we assessed the prognostic impact of pleckstrin homology domain-interacting protein (PHIP) copy number and its relationship to ulceration. PHIP copy number was determined using fluorescence in situ hybridization (FISH) in a tissue microarray cohort of 238 melanomas.

The role of miR-18b in MDM2-p53 pathway signaling and melanoma progression.

Background: Although p53 is inactivated by point mutations in many tumors, melanomas infrequently harbor mutations in the p53 gene. Here we investigate the biological role of microRNA-18b (miR-18b) in melanoma by targeting the MDM2-p53 pathway.

Methods: Expression of miR-18b was examined in nevi (n = 48) and melanoma (n = 92) samples and in melanoma cell lines and normal melanocytes.

Pleckstrin homology domain-interacting protein (PHIP) as a marker and mediator of melanoma metastasis.

Although melanomas with mutant v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) can now be effectively targeted, there is no molecular target for most melanomas expressing wild-type BRAF. Here, we show that the activation of Pleckstrin homology domain-interacting protein (PHIP), promotes melanoma metastasis, can be used to classify a subset of primary melanomas, and is a prognostic biomarker for melanoma. Systemic, plasmid-based shRNA targeting of Phip inhibited the metastatic progression of melanoma, whereas stable suppression of Phip in melanoma cell lines suppressed metastatic potential and prolonged the survival of tumor-bearing mice.