Circulating tumor DNA predicts recurrence and survival in patients with resectable gastric and gastroesophageal junction cancer.

Background: Gastric and gastroesophageal junction (GEJ) cancer represents a significant global health challenge, with high recurrence rates and poor survival outcomes. This study investigates circulating tumor DNA (ctDNA) as a biomarker for assessing recurrence risk in patients with resectable gastric and GEJ adenocarcinomas (AC).

Methods: Patients with resectable gastric and GEJ AC, undergoing perioperative chemotherapy and surgery, were prospectively enrolled.

Genomic alterations in the stepwise progression from normal mucosa to metastasizing oral squamous cell carcinoma.

Introduction: The aim of this study was to investigate the genomic changes that occur in the development from dysplasia, cancer and to regional metastases in patients with oral cavity squamous cell carcinoma (OSCC).

Material And Methods: We included OSCC patients with lymph node metastases at diagnosis, treated with primary surgery at Rigshospitalet, University of Copenhagen in the period 2007-2014. The resected tumor specimens were evaluated by a pathologist, who marked areas of morphologically normal tissue and dysplasia surrounding the cancer, two areas from the cancer tissue, and one area within the lymph node metastases.

Detection of circulating tumor-derived material in peripheral blood of pediatric sarcoma patients: A systematic review.

Background: Detection of circulating tumor-derived material (cTM) in the peripheral blood (PB) of cancer patients has been shown to be useful in early diagnosis, prediction of prognosis, and disease monitoring. However, it has not yet been thoroughly evaluated for pediatric sarcoma patients.

Methods: We searched the PubMed and EMBASE databases for studies reporting the detection of circulating tumor cells, circulating tumor DNA, and circulating RNA in PB of pediatric sarcoma patients.

Circulating Tumor DNA Monitoring Reveals Molecular Progression before Radiologic Progression in a Real-life Cohort of Patients with Advanced Non-small Cell Lung Cancer.

Purpose: The clinical potential of liquid biopsy in patients with advanced cancer is real-time monitoring for early detection of treatment failure. Our study aimed to investigate the clinical validity of circulating tumor DNA (ctDNA) treatment monitoring in a real-life cohort of patients with advanced non-small cell lung cancer (NSCLC).

Experimental Design: Patients with advanced or noncurative locally advanced NSCLC were prospectively included in an exploratory study (NCT03512847).

ProTarget: a Danish Nationwide Clinical Trial on Targeted Cancer Treatment based on genomic profiling - a national, phase 2, prospective, multi-drug, non-randomized, open-label basket trial.

Background: An increasing number of trials indicate that treatment outcomes in cancer patients with metastatic disease are improved when targeted treatments are matched with druggable genomic alterations in individual patients (pts). An estimated 30-80% of advanced solid tumors harbor actionable genomic alterations. However, the efficacy of personalized cancer treatment is still scarcely investigated in larger, controlled trials due to the low frequency and heterogenous distribution of druggable alterations among different histologic tumor types.

Redefining germline predisposition in children with molecularly characterized ependymoma: a population-based 20-year cohort.

Ependymoma is the second most common malignant brain tumor in children. The etiology is largely unknown and germline DNA sequencing studies focusing on childhood ependymoma are limited. We therefore performed germline whole-genome sequencing on a population-based cohort of children diagnosed with ependymoma in Denmark over the past 20 years (n = 43).

Actionable Molecular Alterations Are Revealed in Majority of Advanced Non-Small Cell Lung Cancer Patients by Genomic Tumor Profiling at Progression after First Line Treatment.

: Genomic profiling in advanced Non-Small Cell Lung cancer (NSCLC) can reveal Actionable Molecular Alterations (AMAs). Our study aims to investigate clinical relevance of re-biopsy after first line treatment, by reporting on acquired and persistent AMAs and potential targeted treatments in a real-time cohort of NSCLC patients. : Patients with advanced NSCLC receiving first-line treatment were prospectively included in an observational study (NCT03512847).

Induction of PIK3CA alterations during neoadjuvant letrozole may improve outcome in postmenopausal breast cancer patients.

Purpose: Estrogen receptor positive (ER+) breast cancer constitutes almost 85% of all breast cancer patients and are a genetically highly heterogenic group. Data on the association of somatic alterations to outcome and prognosis are however sparse. In this neoadjuvant endocrine phase II trial including postmenopausal breast cancer patients with ER+, HER2 normal breast cancer, we investigated the rate of pathogenic mutations before and after treatment as well as the association with treatment response and survival.

Circulating cell free DNA during definitive chemo-radiotherapy in non-small cell lung cancer patients - initial observations.

Background: The overall aim was to investigate the change over time in circulating cell free DNA (cfDNA) in patients with locally advanced non-small cell lung cancer (NSCLC) undergoing concurrent chemo-radiotherapy. Furthermore, to assess the possibility of detecting circulating cell free tumor DNA (ctDNA) using shallow whole genome sequencing (sWGS) and size selection.

Methods: Ten patients were included in a two-phase study.

Cell-free DNA in newly diagnosed patients with glioblastoma - a clinical prospective feasibility study.

Glioblastoma (GB) is an incurable brain cancer with limited treatment options. The aim was to test the feasibility of using cell-free DNA (cfDNA) to support evaluation of treatment response, pseudo-progression and whether progression could be found before clinical and/or radiologic progression. CfDNA fluctuated during treatment with the highest levels before diagnostic surgery and at progression.

Application of cell-free DNA for genomic tumor profiling: a feasibility study.

Purpose: Access to genomic tumor material is required to select patients for targeted therapies. However, tissue biopsies are not always feasible and therefore circulating cell-free DNA (cfDNA) has emerged as an alternative. Here we investigate the utility of cfDNA for genomic tumor profiling in the phase I setting.

Enhanced detection of circulating tumor DNA by fragment size analysis.

Existing methods to improve detection of circulating tumor DNA (ctDNA) have focused on genomic alterations but have rarely considered the biological properties of plasma cell-free DNA (cfDNA). We hypothesized that differences in fragment lengths of circulating DNA could be exploited to enhance sensitivity for detecting the presence of ctDNA and for noninvasive genomic analysis of cancer. We surveyed ctDNA fragment sizes in 344 plasma samples from 200 patients with cancer using low-pass whole-genome sequencing (0.

Copenhagen Prospective Personalized Oncology (CoPPO)-Clinical Utility of Using Molecular Profiling to Select Patients to Phase I Trials.

Purpose: We evaluated the clinical benefit of tumor molecular profiling to select treatment in the phase I setting.

Experimental Design: Patients with advanced solid cancers and exhausted treatment options referred to a phase I unit were included in a prospective, single-center, single-arm open-label study (NCT02290522). Tumor biopsies were obtained for comprehensive genomic analysis including whole-exome sequencing and RNA sequencing.

Circulating tumor DNA as a marker of treatment response in BRAF V600E mutated non-melanoma solid tumors.

Purpose: We evaluated longitudinal tracking of BRAF V600E in circulating cell-free DNA (cfDNA) as a marker of treatment response to BRAF inhibitor (BRAFi) combination therapies in non-melanoma solid tumors included in the Copenhagen Prospective Personalized Oncology (CoPPO) program.

Experimental Design: Patients with BRAF V600E-mutated tumors were treated with combination therapies including BRAFi. Quantification of mutant cfDNA from plasma was determined and correlated to clinical outcomes.

Concordance of Mutation Detection in Circulating Tumor DNA in Early Clinical Trials Using Different Blood Collection Protocols.

Background: Small fragments of tumor DNA can be found in the circulation of cancer patients, providing a noninvasive access to tumor material (liquid biopsy). Analysis of circulating tumor DNA (ctDNA) has been used for diagnosis, treatment decisions, and detection of therapy resistance, including in patients with tumors inaccessible for biopsy, making ctDNA an important alternative source of tumor material. Immediate separation of plasma is widely used in standard isolation of cell-free DNA to ensure high quality plasma DNA.

Next-Generation Sequencing-Based Detection of Germline Copy Number Variations in BRCA1/BRCA2: Validation of a One-Step Diagnostic Workflow.

Genetic testing of BRCA1/2 includes screening for single nucleotide variants and small insertions/deletions and for larger copy number variations (CNVs), primarily by Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA). With the advent of next-generation sequencing (NGS), it has become feasible to provide CNV information and sequence data using a single platform. We report the use of NGS gene panel sequencing on the Illumina MiSeq platform and JSI SeqPilot SeqNext software to call germline CNVs in BRCA1 and BRCA2.

Detection of copy number alterations in cell-free tumor DNA from plasma.

Background: Somatic copy number alterations (SCNAs) occurring in tumors can provide information about tumor classification, patient's outcome or treatment targets. Liquid biopsies, incl. plasma samples containing circulating cell-free tumor DNA (ccfDNA) can be used to assess SCNAs for clinical purposes, however specify and reliability of methods have to be tested.

Validation study of HPV DNA detection from stained FNA smears by polymerase chain reaction: Improving the diagnostic workup of patients with a tumor on the neck.

Background: Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) often presents with cystic cervical metastasis and a small primary tumor localized in the palatine tonsils or base of the tongue, which is diagnostically challenging. Testing for HPV DNA in fine-needle aspiration (FNA) smears from metastases may facilitate a targeted diagnostic workup for identifying the primary tumor. This study was designed to assess the ability to detect HPV DNA in FNA smears with polymerase chain reaction (PCR).

Identification of six pathogenic RAD51C mutations via mutational screening of 1228 Danish individuals with increased risk of hereditary breast and/or ovarian cancer.

Germ-line mutations in the RAD51C gene have recently been identified in families with breast and ovarian cancer and have been associated with an increased risk of ovarian cancer. In this study, we describe the frequency of pathogenic RAD51C mutations identified in Danish breast and/or ovarian cancer families. We screened the RAD51C gene in 1228 Danish hereditary breast and/or ovarian cancer families by next-generation sequencing analysis.

Splicing analysis of 14 BRCA1 missense variants classifies nine variants as pathogenic.

Pathogenic germline mutations in the BRCA1 gene predispose carriers to early onset breast and ovarian cancer. Clinical genetic screening of BRCA1 often reveals variants with uncertain clinical significance, complicating patient and family management. Therefore, functional examinations are urgently needed to classify whether these uncertain variants are pathogenic or benign.

Identification of a breast cancer family double heterozygote for RAD51C and BRCA2 gene mutations.

Next-generation sequencing has entered routine genetic testing of hereditary breast cancer. It has provided the opportunity to screen multiple genes simultaneously, and consequently has identified new complex genotypes. Here we report the first identification of a woman double heterozygote for mutations in the RAD51C and BRCA2 genes.