Genomic and Immune Landscape of Non-Small Cell Lung Cancer Brain Metastases.

Purpose: Metastatic spread of non-small cell lung cancer (NSCLC) to the brain is a commonly occurring and challenging clinical problem, often resulting in patient mortality. Systemic therapies including immunotherapy have modest efficacy in treating brain metastases. Moreover, the local immune environment of brain metastases remains poorly described.

The Morphologic and Molecular Heterogeneity of Fumarate Hydratase-deficient Leiomyomas: Integrative Molecular Profiling of Uterine Smooth Muscle Tumors With Histologic Feature Correlation.

The morphologic features of uterine smooth muscle tumors (USMTs) are subject to interobserver variability and are complicated by consideration of features of fumarate hydratase deficiency (FHd) and other morphologic subtypes, with difficult cases occasionally diagnosed as smooth muscle tumor of uncertain malignant potential (STUMP). We compare immunohistochemical findings and detailed morphologic analysis of 45 USMTs by 4 fellowship-trained gynecologic pathologists with comprehensive molecular analysis, focusing on FHd leiomyomas (n=15), compared to a variety of other USMTs with overlapping morphologic features, including 9 STUMPs, 8 usual-type leiomyomas (ULM), 11 apoplectic leiomyomas, and 2 leiomyomas with bizarre nuclei (LMBN). FHd leiomyomas, defined by immunohistochemical (IHC) loss of FH and/or 2SC accumulation, showed FH mutations and/or FH copy loss in all cases, with concurrent TP53 mutations in 2 tumors.

Integrative multi-region molecular profiling of primary prostate cancer in men with synchronous lymph node metastasis.

Localized prostate cancer is frequently composed of multiple spatially distinct tumors with significant inter- and intra-tumoral molecular heterogeneity. This genomic diversity gives rise to many competing clones that may drive the biological trajectory of the disease. Previous large-scale sequencing efforts have focused on the evolutionary process in metastatic prostate cancer, revealing a potential clonal progression to castration resistance.

Development and Validation of an 18-Gene Urine Test for High-Grade Prostate Cancer.

Importance: Benefits of prostate cancer (PCa) screening with prostate-specific antigen (PSA) alone are largely offset by excess negative biopsies and overdetection of indolent cancers resulting from the poor specificity of PSA for high-grade PCa (ie, grade group [GG] 2 or greater).

Objective: To develop a multiplex urinary panel for high-grade PCa and validate its external performance relative to current guideline-endorsed biomarkers.

Design, Setting, And Participants: RNA sequencing analysis of 58 724 genes identified 54 markers of PCa, including 17 markers uniquely overexpressed by high-grade cancers.