Paired plus-minus sequencing is an ultra-high throughput and accurate method for dual strand sequencing of DNA molecules.

Distinguishing real biological variation in the form of single-nucleotide variants (SNVs) from errors is a major challenge for genome sequencing technologies. This is particularly true in settings where SNVs are at low frequency such as cancer detection through liquid biopsy, or human somatic mosaicism. State-of-the-art molecular denoising approaches for DNA sequencing rely on duplex sequencing, where both strands of a single DNA molecule are sequenced to discern true variants from errors arising from single stranded DNA damage.

Integrative transcriptomic and single-cell protein characterization of colorectal carcinoma delineates distinct tumor immune microenvironments associated with overall survival.

Purpose: 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 characteristics of immune composition correlated with prognosis.

Methods: We identified primary and metastatic tumor samples from 31 consented patients, which were profiled with whole-exome sequencing and bulk RNA-seq.

Genomic alterations in the YAP/TAZ pathway are associated with stem cell-like castration-resistant prostate cancer.

Unlabelled: Castration-resistant prostate cancer (CRPC) is an aggressive disease exhibiting multiple epigenomic subtypes: androgen receptor-dependent CRPC-AR, and lineage plastic subtypes CRPC-SCL (stem cell-like), CRPC-WNT (Wnt-dependent), and CRPC-NE (neuroendocrine). By transcriptomic profiling of tissue, and whole-genome sequencing (WGS) of tissue and cell-free DNA (cfDNA) from 500 samples, we relate genomic variants with epigenomic state. We find lineage plasticity is associated with higher epigenomic and genomic heterogeneity.

Unlocking the therapeutic potential of rigosertib as a selective therapy for ovarian cancer.

Precision oncology seeks to exploit tumor-specific drug sensitivities. Traditionally, this is accomplished through the identification and targeting of highly recurrent mutations. This paradigm falls short in ovarian cancer where the oncogenic alterations are more diverse, necessitating an alternate approach for the identification of tumor-specific vulnerabilities.

Polythelia (Supernumerary Nipple): Clinicopathological Characterization of an Atavistic Lesion.

Polythelia refers to the presence of additional nipples typically located along the "milk line." While its atavistic nature and associations with congenital anomalies are well documented, its clinicopathological features are less defined. This retrospective study reviewed 131 lesions diagnosed as polythelia in 112 patients from 1999 to 2024.

Kinome-Focused CRISPR-Cas9 Screens in African Ancestry Patient-Derived Breast Cancer Organoids Identify Essential Kinases and Synergy of EGFR and FGFR1 Inhibition.

Precision medicine approaches to cancer treatment aim to exploit genomic alterations that are specific to individual patients to tailor therapeutic strategies. Yet, some targetable genes and pathways are essential for tumor cell viability even in the absence of direct genomic alterations. In underrepresented populations, the mutational landscape and determinants of response to existing therapies are poorly characterized because of limited inclusion in clinical trials and studies.

Unusual Presentation of Advanced Urothelial Cancer in a Young Patient.

Background/aim: Urothelial carcinoma, common in older adults, is rare in younger populations and even less common in the prostatic urethra. Advanced disease is typically managed with platinum-based chemotherapy, immune checkpoint inhibitors, and targeted therapies. However, rare presentations in young patients with aggressive disease highlight the need for innovative and personalized treatment strategies.

Mesonephric Adenocarcinoma in a Young Male Patient.

Background/aim: Mesonephric adenocarcinoma in males is an exceptionally rare malignancy arising from mesonephric remnants. Accurate diagnosis requires thorough histopathological and molecular analysis.

Case Report: A 33-year-old male presented with right lower quadrant pain, and imaging revealed a pelvic mass compressing adjacent structures.

The Prognostic Role of HPV or p16INK4a Status in Penile Squamous Cell Carcinoma: A Meta-Analysis.

Background: HPV infection is implicated in approximately half of global penile squamous cell carcinoma (PSCC) cases. Previous studies on HPV DNA and p16INK4a status in PSCC have yielded inconclusive prognostic findings. This meta-analysis aims to elucidate the prognostic role of HPV in PSCC by pooling data on disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS).

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.

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).

Whole-Genome Sequencing Analysis of Male Breast Cancer Unveils Novel Structural Events and Potential Therapeutic Targets.

The molecular characterization of male breast cancer (MaBC) has received limited attention in research, mostly because of its low incidence rate, accounting for only 0.5% to 1% of all reported cases of breast cancer each year. Managing MaBC presents significant challenges, with most treatment protocols being adapted from those developed for female breast cancer.