oncogenetic

INTRODUCTION: With the emergence of targeted therapies, there is a need to accurately identify more tumor biomarkers. The EXOMA trial was designed to offer tumor and germline exome sequencing (ES) to patients with solid malignant tumors and facing therapeutic failure. As hereditary cancer predispositions could be identified, with genetic counseling and health management implications, a genetic consultation was systematically established. This design needs to be discussed as genetic human resources are limited and indication of theranostic tests will increase...

The field of mitochondrial genomics has advanced rapidly and has revolutionized disciplines such as molecular anthropology, population genetics, and medical genetics/oncogenetics. However, mtDNA next-generation sequencing (NGS) analysis for matrilineal haplotyping and phylogeographic inference remains hindered by the lack of a consolidated mitogenome database and an efficient bioinformatics pipeline. To address this, we developed a customized human mitogenome database (hMITO DB) embedded in a CLC Genomics workflow for read mapping, variant analysis, haplotyping, and geo-mapping...

Eccrine poroma (EP) is a relatively rare benign adnexal neoplasm that usually affects elderly patients. Its pathogenesis is still under investigation, but recent gene studies have revealed gene fusions as key incidences resulting in oncogenetic pathways. It often presents as a solitary, firm papule, mostly asymptomatic, located on the soles or palms. Due to its clinical and dermoscopic variability, it is characterized as the great imitator. We performed a literature review, aiming to summarize current data on the pathogenetic mechanisms, new dermoscopic features, and novel diagnostic tools that may aid in early diagnosis and proper management of this rare adnexal tumor...

Cancer cells exhibit metabolic reprogramming and bioenergetic alteration, utilizing glucose fermentation for energy production, known as the Warburg effect. However, there are a lack of comprehensive reviews summarizing the metabolic reprogramming, bioenergetic alteration, and their oncogenetic links in gastrointestinal (GI) cancers. Furthermore, the efficacy and treatment potential of emerging anticancer drugs targeting these alterations in GI cancers require further evaluation. This review highlights the interplay between aerobic glycolysis, the tricarboxylic acid (TCA) cycle, and oxidative phosphorylation (OXPHOS) in cancer cells, as well as hypotheses on the molecular mechanisms that trigger this alteration...

To characterize the genomic landscape and leukemogenic pathways of older, newly diagnosed, non-intensively treated patients with AML and to study the clinical implications, comprehensive genetics analyses were performed including targeted DNA sequencing of 263 genes in 604 patients treated in a prospective Phase III clinical trial. Leukemic trajectories were delineated using oncogenetic tree modeling and hierarchical clustering, and prognostic groups were derived from multivariable Cox regression models. Clonal hematopoiesis-related genes (ASXL1, TET2, SRSF2, DNMT3A) were most frequently mutated...

French recommendations for clinical practice Nice-Saint-Paul de Vence 2022-2023: histomolecular diagnosis of endometrial carcinomas The characterisation of endometrial carcinomas has been recently modified and enriched by molecular classification, the integration of which now impacts therapeutic decisions on whether adjuvant therapy should be administered or not in localized tumors, and influences treatment selection in advanced disease. Mandatory information includes histological type according to WHO 2020 classification, histological grade, hormone receptors status and molecular classification, the main new elements to provide being analysis of MMR proteins, p53 status and POLE status in selected cases...

BACKGROUND: Genetic screening for pathogenic variants (PVs) in cancer predisposition genes can affect treatment strategies, risk prediction and preventive measures for patients and families. For decades, hereditary breast and ovarian cancer (HBOC) has been attributed to PVs in the genes BRCA1 and BRCA2, and more recently other rare alleles have been firmly established as associated with a high or moderate increased risk of developing breast and/or ovarian cancer. Here, we assess the genetic variation and tumor characteristics in a large cohort of women with suspected HBOC in a clinical oncogenetic setting...

AIMS: The mutY DNA glycosylase encoded by the MUTYH gene prevents G:C→T:A transversions through the base excision repair DNA repair system. Germline biallelic pathogenic variants in MUTYH cause an adenomatous polyposis called MUTYH-associated polyposis (MAP), an autosomal recessive disease (OMIM: 608456), with an increased risk of colorectal cancer. Digestive lesions in this context show an excess of G:C→T:A transversions, individualising a specific mutational signature associated with MUTYH deficiency called signature SBS36...

INTRODUCTION: Signet ring cell carcinoma accounts for 35% to 45% of all gastric cancer. Despite the acknowledgment of its more aggressive pathological features, various controversies surrounding this topic still exist. Thus, we investigate the clinical pathological characteristics and survival prognostic significance of signet ring cell components in patients affected by gastric cancer. METHODS: From January 2004 to December 2020, in a retrospective study, we enrolled 404 patients with gastric cancer who were curatively treated in our department...

BACKGROUND: Cancer predisposition syndromes (CPSs) are responsible for at least 10% of cancer diagnoses in children and adolescents, most of which are not clinically recognised prior to cancer diagnosis. A variety of clinical screening guidelines are used in healthcare settings to help clinicians detect patients who have a higher likelihood of having a CPS. The McGill Interactive Pediatric OncoGenetic Guidelines (MIPOGG) is an electronic health decision support tool that uses algorithms to help clinicians determine if a child/adolescent diagnosed with cancer should be referred to genetics for a CPS evaluation...

Currently, ovarian cancer (OC) is a target of intense biomarkers research because of its frequent late diagnosis and poor prognosis. Serum determination of Human epididymis protein 4 (HE4) is a very important early detection test. Most interestingly, HE4 plays a unique role in OC as it has been implicated not only in OC diagnosis but also in the prognosis and recurrence of this lethal neoplasm, actually acting as a clinical biomarker. There are several evidence about the predictive power of HE4 clinically, conversely less has been described concerning its role in OC oncogenesis...

BACKGROUND/AIM: Mesotheliomas are tumors similar to, and probably derived from, mesothelial cells. They carry acquired chromosomal rearrangements, deletions affecting CDKN2A, pathogenetic polymorphisms in NF2, and fusion genes which often contain the promiscuous EWSR1, FUS, and ALK as partner genes. Here, we report the cytogenomic results on two peritoneal mesotheliomas. MATERIALS AND METHODS: Both tumors were examined using G-banding with karyotyping and array comparative genomic hybridization (aCGH)...

BACKGROUND/OBJECTIVES: Genetic counselling (GC) is a key step in the identification of inherited germline mutations. However, the oncogenetic practices are poorly described for pancreatic adenocarcinoma (PA) in Europe. The CAPANCOGEN study aimed to describe the GC referral practices in France and assess the implementation of international guidelines in patients with PA. METHODS: Information about GC referrals with PA was collected in 13 French centres from September 2019 to October 2021...

BACKGROUND: Disulfidptosis is a recently discovered form of cell death. However, its biological mechanisms in bladder cancer (BCa) are yet to be understood. METHODS: Disulfidptosis-related clusters were identified by consensus clustering. A disulfidptosis-related gene (DRG) prognostic model was established and verified in various datasets. A series of experiments including qRT-PCR, immunoblotting, IHC, CCK-8, EdU, wound-healing, transwell, dual-luciferase reporter, and ChIP assays were used to study the biological functions...

In early 1995, I established the oncogenetics service at the Genetics Institute of the Sheba Medical Center in Israel. The purpose of this article is to describe the key points and issues that were raised throughout my personal journey since then: physician and public awareness; ethical and legal issues; guidelines for oncogenetic counseling; the development of oncogenetic testing within the unique Israeli reality of the limited spectrum of BRCA1 and BRCA2 mutations; high-risk vs. population screening; and the definition and implementation of guidelines for surveillance of asymptomatic mutation carriers...

In Romania, breast cancer (BC) is the most common malignancy in women. However, there is limited data on the prevalence of predisposing germline mutations in the population in the era of precision medicine, where molecular testing has become an indispensable tool in cancer diagnosis, prognosis, and therapeutics. Therefore, we conducted a retrospective study to determine the prevalence, mutational spectrum, and histopathological prediction factors for hereditary breast cancer (HBC) in Romania. A cohort of 411 women diagnosed with BC selected upon NCCN v...

In view of the use of oncogenetics as a lever for proposing new-targeted therapies whose indications are expanding, this article provides an overview of this discipline in the French overseas departments and regions (DROM). Contrary to the metropolitan departments, where the number of consultations exceeds 100 consultations per 100,000 inhabitants for most centres in 2019, the number of consultations in the DROMs remains insufficient to meet the national average of 117 per 100,000 inhabitants. The financial and structural support offered by the INCa and the DGOS since 2003 has contributed favourably to the deployment of this activity in metropolitan France...

The adrenocortical carcinoma (ACC) is a primary malignant tumor developed from the adrenal cortex, defined by a Weiss score≥3. Its prognosis is poor and depends mainly on the stage of the disease at diagnosis. Care is organized in France by the multidisciplinary expert centers of the national ENDOCAN-COMETE "Adrenal Cancers" network, certified by the National Cancer Institute. This document updates the guidelines for the management of ACC in adults based on the most robust data in the literature. It's divided into 11 chapters: (1) circumstances of discovery; (2) pre-therapeutic assessment; (3) diagnosis of ACC; (4) oncogenetics; (5) prognostic classifications; (6) treatment of hormonal hypersecretion; (7) treatment of localized forms; (8) treatment of relapses; (9) treatment of advanced forms; (10) follow-up; (11) the particular case of ACC and pregnancy...

BACKGROUND: Inherited mutations in the breast cancer susceptibility genes BRCA1 and BRCA2 (BRCA1/2) confer high risks of breast and ovarian cancer. Because the contribution of BRCA1/2 germline mutations to BC in the Northeastern population of Morocco remains largely unknown, we conducted this first study to evaluate the prevalence and the phenotypic spectrum of two BRCA1/2 pathogenic mutations (the founder BRCA1 c.5309G>T and BRCA2 c.1310_1313delAAGA). This choice was also argued by the presence of an apparent specific geographical connection of these mutations and the Northeastern region of Morocco...

Oncogenetic graphical models are crucial for understanding cancer progression by analyzing the accumulation of genetic events. These models are used to identify statistical dependencies and temporal order of genetic events, which helps design targeted therapies. However, existing algorithms do not account for temporal differences between samples in oncogenetic analysis. This paper introduces Timed Hazard Networks (TimedHN), a new statistical model that uses temporal differences to improve accuracy and reliability...