Emerging molecular phenotypes and potential therapeutic targets in esophageal and gastric adenocarcinoma unearthed by whole genome and transcriptome analyses.

Background: Adenocarcinoma of the esophagus and stomach demands a deeper molecular understanding to advance treatment strategies and improve patient outcomes. Here, we profiled the genome and transcriptome landscape of these cancers, explored molecular characteristics that are undetectable by other sequencing platforms, and analyzed their potential clinical ramifications.

Methods: Our study employed state-of-the-art integrative analyses of whole genome and transcriptome sequencing on 51 matched tumor and germline samples from 46 patients.

Novel structural variants that impact cell cycle genes are elucidated in metastatic gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the digestive tract. Despite multiple therapeutic advances, patients with advanced disease frequently develop resistance to tyrosine kinase inhibitors (TKIs), and therefore represent a therapeutic challenge. We employed whole genome sequencing (WGS) on three metastatic GISTs refractory to various TKIs and explored a publicly available cohort of 499 GISTs.

Enhancing the detection of clinically relevant biomarkers in advanced uterine and tubo-ovarian carcinomas through genome-wide analysis.

Background: Advanced-stage tube-ovarian cancers (TOC) and uterine cancers (UC) significantly contribute to cancer mortality. While surgery achieves clinical remission in most cases, recurrence often necessitates systemic therapy. Recent molecular phenotype studies have advanced targeted therapies.

Whole genome sequencing elucidates etiological differences in MCPyV-negative Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine neoplasm of the skin. Immunosuppression, ultraviolet radiation and the integration of Merkel cell polyomavirus (MCPyV) have all been shown to be involved in the pathogenesis of this malignancy. We performed whole genome sequencing on two MCPyV-negative cases of MCC that demonstrated very different clinical presentations and outcomes, and mutational profiles.

Integrative Transcriptomic and Single-Cell Protein Characterization of Colorectal Carcinoma Delineates Distinct Tumor Immune Microenvironments Associated with Overall Survival.

Colorectal carcinoma (CRC) is a heterogeneous group of tumors with varying therapeutic response and prognosis, and evidence suggests the tumor immune microenvironment (TIME) plays a pivotal role. Using advanced molecular and spatial biology technologies, we aimed to evaluate the TIME in patients with CRC to determine whether specific alterations in the immune composition correlated with prognosis. We identified primary and metastatic tumor samples from 31 consented patients, which were profiled with whole-exome sequencing and bulk RNA-seq.

Notch signaling suppresses neuroendocrine differentiation and alters the immune microenvironment in advanced prostate cancer.

Notch signaling can have either an oncogenic or tumor-suppressive function in cancer depending on the cancer type and cellular context. While Notch can be oncogenic in early prostate cancer, we identified significant downregulation of the Notch pathway during prostate cancer progression from adenocarcinoma to neuroendocrine (NE) prostate cancer, where it functions as a tumor suppressor. Activation of Notch in NE and Rb1/Trp53-deficient prostate cancer models led to phenotypic conversion toward a more indolent, non-NE state with glandular features and expression of luminal lineage markers.

Immune-based Therapies for Penile Cancer.

This article reviews penile squamous cell carcinoma (PSCC), a rare genitourinary cancer that has been increasing in prevalence. It discusses emerging therapies, focusing on immunotherapy, vaccine therapy, and cell-based treatments, especially in the context of human papillomavirus-related PSCC. Factors influencing these therapies are discussed.

Overview of Systemic Therapies in Penile Cancer.

Penile cancer (PC), although rare, poses significant challenges in both diagnosis and treatment. Penile squamous cell carcinoma (PSCC) represents the most common histologic subtype of PC, accounting for approximately 95% of cases. With limited therapeutic options available, systemic therapies have emerged as critical components in the management of advanced PSCC.

Optimization of Fluorescence In Situ Hybridization Protocols in the Era of Precision Medicine.

Fluorescence in situ hybridization (FISH) is a cytogenetic assay that is widely used in both clinical and research settings to validate genetic aberrations. Simple in principle, it is based on denaturation and hybridization of a DNA probe and its complementary sequence; however, it is subject to continuous optimization. Here we share how in-house FISH can be optimized using different control tissues to visualize and ultimately validate common and novel genetic abnormalities unearthed by next-generation sequencing (NGS).

The importance of escalating molecular diagnostics in patients with low-grade pediatric brain cancer.

Pilocytic astrocytomas are the most common pediatric brain tumors, typically presenting as low-grade neoplasms. We report two cases of pilocytic astrocytoma with atypical tumor progression. Case 1 involves a 12-yr-old boy with an unresectable suprasellar tumor, negative for rearrangement but harboring a p.

Case report: Metastatic urothelial cancer with an exceptional response to immunotherapy and comprehensive understanding of the tumor and the tumor microenvironment.

Although immune checkpoint inhibitors (ICIs) are increasingly used as second-line treatments for urothelial cancer (UC), only a small proportion of patients respond. Therefore, understanding the mechanisms of response to ICIs is critical to improve clinical outcomes for UC patients. The tumor microenvironment (TME) is recognized as a key player in tumor progression and the response to certain anti-cancer treatments.

GLI1 -Rearranged Enteric Tumor : Expanding the Spectrum of Gastrointestinal Neoplasms With GLI1 Gene Fusions.

GLI1 encodes a transcription factor that targets cell cycle regulators affecting stem cell proliferation. GLI1 gene fusions were initially described in pericytomas with a t[7;12] translocation and more recently in gastric plexiform fibromyxomas and gastroblastomas. This study describes the clinicopathologic, immunohistochemical, and molecular features of three intestinal-based neoplasms harboring GLI1 gene fusions.

Weakly-supervised tumor purity prediction from frozen H&E stained slides.

Background: Estimating tumor purity is especially important in the age of precision medicine. Purity estimates have been shown to be critical for correction of tumor sequencing results, and higher purity samples allow for more accurate interpretations from next-generation sequencing results. Molecular-based purity estimates using computational approaches require sequencing of tumors, which is both time-consuming and expensive.

Prevalence of programmed death ligand-1 in patients diagnosed with non-small cell lung cancer in Lebanon.

Introduction: Programmed death ligand-1 expression has been shown to be a good predictor of response to cancer therapy with checkpoint inhibitors. Its expression varies among different tumor types and among non-small cell lung cancer patients with different clinical and demographic characteristics. The prevalence and determinants of programmed death ligand-1 expression have been previously reported from various regions of the world, but data from Lebanon are lacking.

Prognostic indicators of survival in patients with small-cell lung cancer at a tertiary care center in Lebanon.

Objective: Small-cell lung cancer is a very aggressive tumor associated with high invasiveness and ease of metastasis and therefore poor prognosis. In the literature, several demographical, clinical as well as pathological factors including age, stage, gender and smoking were cited as independent prognosticators of survival.

Material And Methods: This is a retrospective cohort study that includes 222 patients diagnosed with small-cell lung cancer between 2010 and 2019.

Neoadjuvant chemotherapy and Avelumab in early stage resectable nonsmall cell lung cancer.

Multiple randomized studies have shown that combination of chemotherapy and immune checkpoint inhibitors (ICIs) leads to better response rates and survival as compared to chemotherapy alone in the advanced stage of NSCLC. Data suggesting a benefit to using ICIs in the neoadjuvant therapy of patients with early stage NSCLC are emerging. Eligible subjects were treatment naïve patients with stage IB, II, and resectable IIIA NSCLC.

Association of various dietary habits and risk of lung cancer: an updated comprehensive literature review.

Lung cancer remains the leading cause of cancer death in both men and women worldwide. Tobacco smoking remains the single most important factor. Recent research has focused on the role of nutrition and dietary habits on lung tumorigenesis.