A5057851013- Prostate Cancer Treatment and Research
- PARP inhibition in cancer therapy
- Cancer Immunotherapy and Biomarkers
- Science, Research, and Medicine
- Neuroendocrine Tumor Research Advances
- Lung Cancer Research Studies
- Neuroblastoma Research and Treatments
- Cancer Genomics and Diagnostics
- Computational Drug Discovery Methods
- Immunotherapy and Immune Responses
- Glutathione Transferases and Polymorphisms
- Immune Cell Function and Interaction
- Breast Lesions and Carcinomas
- Immune cells in cancer
- Virus-based gene therapy research
- Breast Cancer Treatment Studies
- CAR-T cell therapy research
- Nanoplatforms for cancer theranostics
- Radiopharmaceutical Chemistry and Applications
- Cancer Research and Treatments
- Salivary Gland Tumors Diagnosis and Treatment
- Sarcoma Diagnosis and Treatment
- Tumors and Oncological Cases
- Infectious Diseases and Mycology
- Cancer and Skin Lesions
University of Minnesota System
2024-2025
University of Minnesota
2023-2024
Twin Cities Orthopedics
2023-2024
University of Minnesota Medical Center
2023
Memorial Sloan Kettering Cancer Center
2017-2020
University of Basel
2018
University of Bologna
2018
University of Nottingham
2018
Thomas Jefferson University Hospital
2018
Ospedale Bellaria
2018
Adenomyoepithelioma of the breast is a rare tumor characterized by epithelial-myoepithelial differentiation, whose genetic underpinning largely unknown. Here we show through whole-exome and targeted massively parallel sequencing analysis that whilst estrogen receptor (ER)-positive adenomyoepitheliomas display PIK3CA or AKT1 activating mutations, ER-negative harbor highly recurrent codon Q61 HRAS hotspot which co-occur with PIK3R1 mutations. In two- three-dimensional cell culture models,...
Abstract Granular cell tumors (GCTs) are rare that can arise in multiple anatomical locations, and characterized by abundant intracytoplasmic granules. The genetic drivers of GCTs currently unknown. Here, we apply whole-exome sequencing targeted analysis to reveal mutually exclusive, clonal, inactivating somatic mutations the endosomal pH regulators ATP6AP1 or ATP6AP2 72% GCTs. Silencing these genes vitro results impaired vesicle acidification, redistribution compartments, accumulation...
Abstract Background Natural killer (NK) cells are non-antigen specific innate immune that can be redirected to targets of interest using multiple strategies, although none currently FDA-approved. We sought evaluate NK cell infiltration into tumors develop an improved understanding which histologies may most amenable cell-based therapies in the developmental pipeline. Methods DNA (targeted/whole-exome) and RNA (whole-transcriptome) sequencing was performed from 45 cancer types ( N = 90,916...
Aims Solid papillary breast carcinoma resembling the tall cell variant of thyroid neoplasms ( BPTC ), also known as solid with reverse polarity, is a rare histological type cancer that resembles morphologically carcinoma. s are characterised by IDH 2 R172 hotspot somatic mutations or mutually exclusive TET mutations, concurrently affecting PI 3K pathway‐related genes. We sought to characterise their histology and investigate frequency PIK 3 CA in an independent cohort s, well conventional...
Mono-allelic germline pathogenic variants in the Partner And Localizer of BRCA2 (PALB2) gene predispose to a high-risk breast cancer development, consistent with role PALB2 homologous recombination (HR) DNA repair. Here, we sought define repertoire somatic genetic alterations PALB2-associated cancers (BCs), and whether BCs display bi-allelic inactivation and/or genomic features HR-deficiency (HRD). Twenty-four patients mutations were analyzed by whole-exome sequencing (WES, n = 16) or...
Polymorphous adenocarcinoma (PAC) shows histologic diversity with streaming and targetoid features whereas cribriform of salivary gland (CASG) demonstrates predominantly solid patterns glomeruloid structures optically clear nuclei. Opinions diverge on whether CASG represents a separate entity or variant PAC. We aimed to assess the level agreement among 25 expert Head Neck pathologists in classifying these tumors. Digital slides 48 cases were reviewed classified as: PAC, CASG, tumors ≥50%...
B7-H3 (CD276) is a transmembrane glycoprotein of the B7 immune checkpoint superfamily that has emerged as promising therapeutic target. To better understand applicability B7-H3-directed therapies, we analyzed 156,791 samples comprising 50 cancer types to interrogate clinical, genomic, transcriptomic, and immunologic correlates mRNA expression. DNA (592-gene/whole-exome) RNA (whole-transcriptome) sequencing was performed from submitted Caris Life Sciences. high versus low expression based on...
Abstract Patients with prostate cancer (PC) generally do not respond favorably to immune checkpoint inhibitors, which may be due a low abundance of tumor-infiltrating lymphocytes even when mutational load is high. Here, we identified patient who presented high-grade primary two adjacent tumor nodules. While both nodules were mismatch repair-deficient (MMRd), exhibited pathogenic MSH2 and MSH6 alterations, had high burden (TMB), demonstrated microsatellite instability (MSI), they markedly...
Abstract Neuroendocrine neoplasms (NENs) encompass a diverse set of malignancies with limited precision therapy options. Recently, therapies targeting DLL3 have shown clinical efficacy in aggressive NENs, including small cell lung cancers and neuroendocrine prostate cancers. Given the continued development expansion DLL3-targeted therapies, we sought to characterize expression identify its molecular correlates across non-neuroendocrine Here, interrogated paired DNA RNA-sequencing from 1,589...
<p>DLL3-high versus -low hazard ratios across cancer.</p>
<p>Demographics of NEN samples by anatomic site</p>
<p>Supplementary Figure S1: UMAP view of NEN samples across diverse anatomic sites. Samples were unbiasedly clustered based off the top 1,000 variably expressed genes and annotated using (A) DLL3 expression level (B) site origin.</p>
<div>Abstract<p>Neuroendocrine neoplasms (NEN) encompass a diverse set of malignancies with limited precision therapy options. Recently, therapies targeting DLL3 have shown clinical efficacy in aggressive NENs, including small cell lung cancers and neuroendocrine prostate cancers. Given the continued development expansion DLL3-targeted therapies, we sought to characterize expression identify its molecular correlates across non-neuroendocrine Here, interrogated paired DNA...
<p>Correlates of <i>DLL3</i> expression with immune repertoire, alternative targets, and non-neuroendocrine cancers. <b>A,</b> Radar plots displaying differences in infiltrates between <i>DLL3</i>-high -low NENs. <b>B,</b> Ridgeline comparing the density precision targets NENs site-matched ADCs. <b>C,</b> Violin plots, bar heatmap <i>DLL3</i>, percent <i>DLL3</i>-high, hazard ratio, respectively, across...
<p>Supplementary Figure S4: Genetic dependencies in neuroendocrine cancer cell lines. Scatterplot displaying gene depletion effects NEN lines represented DepMap. Data points represent the mean effect of each target. Highlighted genes potential (gene < -0.5).</p>
<p>Supplementary Figure S3: Immune repertoire of DLL3-high versus –low NENs across anatomic sites. Stacked radar plots comparing the imputed cell fractions immune cells between and -low samples in (A) lung NECs, (B) NETs, (C) prostate NENs, (D) bladder NENs. *q < 0.05, **q 0.01</p>
<p>Supplementary Figure S2: Correlations between expression of DLL3, ASCL1, and NEUROD1 across select NEN sites. Scatterplots displaying the DLL3 vs ASCL1 (top) (bottom) Expression is depicted as log(TPM + 0.001). Spearman correlations corresponding p-values are shown for each site.</p>
<p>Expression patterns of <i>DLL3</i> across NENs. <b>A,</b> Violin plots displaying expression in NENs and ADCs originating from the lung or prostate. <b>B,</b> by histologic grade. Bar above show proportion grade that was defined as <i>DLL3</i>-high. LNEC, large cell neuroendocrine carcinoma; SNEC, small carcinoma. <b>C,</b> Differences genetic alterations between <i>DLL3</i>-high -low NENs, well breakdown...
<p>DLL3-high versus -low hazard ratios across NEN anatomic sites</p>
<p>Supplementary Figure S4: Genetic dependencies in neuroendocrine cancer cell lines. Scatterplot displaying gene depletion effects NEN lines represented DepMap. Data points represent the mean effect of each target. Highlighted genes potential (gene < -0.5).</p>
<p>Supplementary Figure S1: UMAP view of NEN samples across diverse anatomic sites. Samples were unbiasedly clustered based off the top 1,000 variably expressed genes and annotated using (A) DLL3 expression level (B) site origin.</p>
<p>Supplementary Figure S3: Immune repertoire of DLL3-high versus –low NENs across anatomic sites. Stacked radar plots comparing the imputed cell fractions immune cells between and -low samples in (A) lung NECs, (B) NETs, (C) prostate NENs, (D) bladder NENs. *q < 0.05, **q 0.01</p>
<p>DLL3-high versus -low hazard ratios across NEN anatomic sites</p>