Proteomics-Based Analysis of Laser-Capture Micro-dissected, Formalin-Fixed Paraffin-Embedded Tissue Samples.

The ability to bring spatial resolution to omics studies enables a deeper understanding of cell populations and interactions in biological tissues. In the case of proteomics, single-cell and spatial approaches have been particularly challenging, due to limitations in sensitivity and throughput relative to other omics fields. Recent developments at the level of sample handling, chromatography, and mass spectrometry have set the stage for proteomics to be established in these new disciplines.

Innovative label-free lymphoma diagnosis using infrared spectroscopy and machine learning on tissue sections.

The diagnosis of lymphomas is challenging due to their diverse histological presentations and clinical manifestations. There is a need for inexpensive tools that require minimal expertise and are accessible for routine laboratories. Contrastingly, current conventional diagnostic methods are often found only in specialized environments.

Pilot Study on the Use of Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy for Diagnosing and Characterizing Cardiac Amyloidosis.

Amyloidosis diagnosis relies on Congo red staining with immunohistochemistry and immunofluorescence for subtyping but lacks sensitivity and specificity. Laser-microdissection mass spectroscopy offers better accuracy but is complex and requires extensive sample preparation. Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy offers a promising alternative for amyloidosis characterization.

Acute myeloid leukemia stem cell signature gene EMP1 is not an eligible therapeutic target.

Background: Relapse in pediatric acute myeloid leukemia (pedAML) patients is known to be associated with residual leukemic stem cells (LSC). We have previously shown that epithelial membrane protein 1 (EMP1) is significantly overexpressed in LSC compared to hematological stem cell fractions. EMP1 was also documented as part of the 17-gene stemness score and a 6-membrane protein gene score, both correlating high EMP1 expression with worse overall survival.

Exploring the cell-free total RNA transcriptome in diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma patients as biomarker source in blood plasma liquid biopsies.

Introduction: Diffuse large B-cell lymphoma (DLBCL) and primary mediastinal B-cell lymphoma (PMBCL) are aggressive histological subtypes of non-Hodgkin's lymphoma. Improved understanding of the underlying molecular pathogenesis has led to new classification and risk stratification tools, including the development of cell-free biomarkers through liquid biopsies. The goal of this study was to investigate cell-free RNA (cfRNA) biomarkers in DLBCL and PMBCL patients.

Targeting hyperactive platelet-derived growth factor receptor-β signaling in T-cell acute lymphoblastic leukemia and lymphoma.

T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) are rare aggressive hematologic malignancies. Current treatment consists of intensive chemotherapy leading to 80% overall survival but is associated with severe toxic side effects. Furthermore, 10-20% of patients still die from relapsed or refractory disease providing a strong rationale for more specific, targeted therapeutic strategies with less toxicities.

Application of an Ultrasensitive NGS-Based Blood Test for the Diagnosis of Early-Stage Lung Cancer: Sensitivity, a Hurdle Still Difficult to Overcome.

Diagnosis of lung cancer requires histological examination of a tissue sample, which in turn requires an invasive procedure that cannot always be obtained. Circulating tumor DNA can be reliably detected in blood samples of advanced-stage lung cancer patients and might also be a minimally invasive alternative for early-stage lung cancer detection. We wanted to explore the potential of targeted deep sequencing as a test for the diagnosis of early-stage lung cancer in combination with imaging.

Systemic mastocytosis with myeloid sarcoma and B-CLL: molecular and clonal heterogeneity in a rare case of SM-AHN with review of literature.

Background: Systemic mastocytosis (SM) is a rare myeloproliferative disease that results from a clonal proliferation of abnormal mast cells in one or more extra-cutaneous organs. Systemic mastocytosis with an associated hematological neoplasm (SM-AHN) is the second most common subgroup and is diagnosed when WHO criteria for both SM and a hematological neoplasm of non-mast cell lineage are met. The SM-AHN category as currently proposed is highly heterogeneous in terms of pathogenesis, clinical presentation, and prognosis.

Shallow whole-genome sequencing: a useful, easy to apply molecular technique for CNA detection on FFPE tumor tissue-a glioma-driven study.

Copy number alterations (CNAs) have increasingly become part of the diagnostic algorithm of glial tumors. Alterations such as homozygous deletion of CDKN2A/B, 7 +/ 10 - chromosome copy number changes or EGFR amplification are predictive of a poor prognosis. The codeletion of chromosome arms 1p and 19q, typically associated with oligodendroglioma, implies a more favorable prognosis.

The feasibility of using liquid biopsies as a complementary assay for copy number aberration profiling in routinely collected paediatric cancer patient samples.

Background: Paediatric tumours are often characterised by the presence of recurrent DNA copy number alterations (CNAs). These DNA copy number profiles, obtained from a tissue biopsy, can aid in the correct prognostic classification and therapeutic stratification of several paediatric cancer entities (e.g.

Myxoid pleomorphic liposarcoma-a clinicopathologic, immunohistochemical, molecular genetic and epigenetic study of 12 cases, suggesting a possible relationship with conventional pleomorphic liposarcoma.

Myxoid pleomorphic liposarcoma is a recently defined subtype of liposarcoma, which preferentially involves the mediastinum of young patients and shows mixed histological features of conventional myxoid liposarcoma and pleomorphic liposarcoma. While myxoid pleomorphic liposarcoma is known to lack the EWSR1/FUS-DDIT3 fusions characteristic of the former, additional genetic data are limited. To further understand this tumor type, we extensively examined a series of myxoid pleomorphic liposarcomas by fluorescence in situ hybridization (FISH), shallow whole genome sequencing (sWGS) and genome-wide DNA methylation profiling.

Shallow-depth sequencing of cell-free DNA for Hodgkin and diffuse large B-cell lymphoma (differential) diagnosis: a standardized approach with underappreciated potential.

Shallow-depth sequencing of cell-free DNA, a cheap and standardized approach to obtain molecular information on tumors non-invasively, is insufficiently explored for lymphoma diagnosis and disease follow-up. This study collected 318 samples, including longitudinal liquid and paired solid biopsies, from a prospectively recruited cohort of 38 Hodgkin lymphoma (HL) and 85 aggressive B-cell non- HL patients, represented by 81 diffuse large B-cell lymphoma (DLBCL) cases. Following sequencing, copy number alterations and viral read fractions were derived and analyzed.

Myxoid hepatocellular adenoma, a rare variant of hepatocellular adenoma with distinct imaging features: A case report with immunohistochemical and molecular analysis and literature review.

Preoperative imaging and histopathology, immunohistochemistry and molecular analysis after resection of 2 hepatocellular adenomas (HCAs) (20 and 2cm) in a 53-year-old female patient were performed. On imaging, the large lesion resembled a myxoid HCA, while the small lesion resembled a more conventional HCA with a small myxoid/fluid area. On microscopy, the large lesion showed cords and nests of hepatocytes embedded in abundant myxoid matrix, while the small lesion resembled a conventional HCA with small foci of myxoid change and serosities; both consistent with a myxoid HCA.

Shallow whole-genome sequencing of plasma cell-free DNA accurately differentiates small from non-small cell lung carcinoma.

Background: Accurate lung cancer classification is crucial to guide therapeutic decisions. However, histological subtyping by pathologists requires tumor tissue-a necessity that is often intrinsically associated with procedural difficulties. The analysis of circulating tumor DNA present in minimal-invasive blood samples, referred to as liquid biopsies, could therefore emerge as an attractive alternative.

Detection of Copy Number Alterations by Shallow Whole-Genome Sequencing of Formalin-Fixed, Paraffin-Embedded Tumor Tissue.

Context.—: In routine clinical practice, tumor tissue is stored in formalin-fixed, paraffin-embedded blocks. However, the use of formalin-fixed, paraffin-embedded tissue for genome analysis is challenged by poorer DNA quality and quantity.

Biallelic and monoallelic ESR2 variants associated with 46,XY disorders of sex development.

Purpose: Disorders or differences of sex development (DSDs) are rare congenital conditions characterized by atypical sex development. Despite advances in genomic technologies, the molecular cause remains unknown in 50% of cases.

Methods: Homozygosity mapping and whole-exome sequencing revealed an ESR2 variant in an individual with syndromic 46,XY DSD.

Shallow Whole Genome Sequencing on Circulating Cell-Free DNA Allows Reliable Noninvasive Copy-Number Profiling in Neuroblastoma Patients.

Neuroblastoma (NB) is a heterogeneous disease characterized by distinct clinical features and by the presence of typical copy-number alterations (CNAs). Given the strong association of these CNA profiles with prognosis, analysis of the CNA profile at diagnosis is mandatory. Therefore, we tested whether the analysis of circulating cell-free DNA (cfDNA) present in plasma samples of patients with NB could offer a valuable alternative to primary tumor DNA for CNA profiling.