Glioblastoma is the most common primary malignant brain tumor. Despite treatments combining excisional surgery, chemotherapy, and radiotherapy, overall survival remains low and the incidence of tumor recurrence remains high. Advances in the understanding of the disease, particularly its molecular biology and the mechanisms of action of systemic and radiotherapeutic treatments, as well as the development of image-guided surgical techniques, offer hope for the control of this hitherto incurable disease.

A personal or family history of cancer has now become the primary cause of genetic consultations. In recent years, various genes have been identified that are associated with a more or less marked genetic predisposition to the development of cancers. The syndrome associated with the hereditary risk of breast and ovarian cancer and the Lynch syndrome are the most frequent ones, but there are many other, much less common, situations associated with familial cancer risk. In most cases, there are clear recommendations regarding the indications for genetic testing and the follow-up of patients identified as having a predisposition to cancer. At the CHU of Liège, we currently perform more than 1.400 oncogenetic consultations per year and we maintain a positivity rate of genetic tests performed in this indication higher than 10%. In this way, we allow a multidisciplinary care of patients with a high oncological risk and participate in a prevention and surveillance activity. We also pay increasing attention to the hereditary risk associated with pediatric cancers and to patients with multiple cancers, especially when these develop at an early age. Finally, the oncogenetic consultation must consider the psychological, ethical and legal aspects of a diagnosis that involves the patient and his or her future, but also the whole family.

The development of new targeted therapies in non-small cell lung carcinoma (NSCLC) depends on a better understanding of the molecular basis of carcinogenesis, a knowledge of the role of molecular aberrations in disease progression and the development of molecular biology platforms with the capacity to identify new biomarkers. In the current article, we review the techniques routinely used in cancer molecular biology platforms as well as new techniques under development. These new NSCLC biomarkers have been made available to clinicians and biologists in parallel with the development of targeted drugs. New molecular abnormalities of EGFR exon 20, HER2, MET, RET, BRAF, ROS1 and NTRK have been identified and there have been clinical trials of the most innovative targeted drugs.

Anaplastic thyroid cancer (ATC) is among the most aggressive cancers with a median overall survival of 4 months and a disease-specific mortality of close to 100%. As soon as the diagnosis is suspected or established, urgent referral to an experienced multidisciplinary center is imperative. Chemotherapy has limited efficacy. Molecular analyses, together with the availability of novel targeted therapies and immunotherapies, now permit to improve outcomes. In particular, targeted therapy with dabrafenib and trametinib is indicated as first-line therapy for BRAF V600E-mutated ATC.

Sarcoma consists in a group of rare malignant tumours of mesenchymal origin characterized by their vast clinical, pathological and biological heterogeneity. The pathological diagnosis of sarcoma relies classically of the differentiation features of tumour cells, with dozens of different tumour subtypes described in the last international classifications. Over the last decades, the advances in the development of new techniques of molecular biology have led to a major complexification of sarcoma classification, with the identification of multiple and specific molecular alterations that have led to significant changes for patients diagnostic, prognostic and therapeutic management. This review aims at giving an overview on the current knowledge of the molecular biology of soft tissue sarcoma, and emphasizes on their consequences for the daily management of patients.

Malignant Triton tumour (MTT) is a subtype of malignant peripheral nerve sheaths tumour (MPNST) with exclusive heterologous rhabdomyosarcomatous contingent. MTT is rare and of poor prognosis. This entity illustrates the great heterogeneity of MPNST, the diagnosis of which is difficult in the absence of a specific marker, especially in sporadic forms. Although MTT preferentially develop in patients with type 1 neurofibromatosis, sporadic cases may occur. We herein present a case of MTT of the left arm, occurring in a 74-year-old patient, without clinical context of NF1. The fast-growing tumour reached 9.2cm of greater dimension at the time of surgical excision. Histology showed a spindle cell sarcoma with rhabdoid cell areas expressing myogenin. In the absence of neural crest markers expression, the diagnosis of MPNST was based on a significant loss of expression of the histone 3 tri-methylated lysine 27, a classical although not specific epigenetic mark for this sarcoma group, and on the identification of the heterologous rhabdomyosarcomatous contingent, previously described in the context of MTT.

Richter syndrome (RS) is defined as the occurrence of an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL) and rarely Hodgkin lymphoma (HL), in a patient with prior or concomitant chronic lymphocytic leukemia (CLL). RS is estimated to occur in 0.5-1 % per year and is associated with adverse outcome. In the vast majority of patients (80 %), RS is clonally related to the prior CLL. Those with unrelated RS appear to have better outcome. The therapeutic approach is based on those of de novo DLBCL or HL. However, even with modern immunochemotherapy regimens, response rate remains low. In eligible patients with related RS, a consolidation by autologous or allogeneic stem-cell transplantation must be proposed. Combinations including therapies targeting BCR or BCL2 and effective in CLL are currently being evaluated in RS. Novels immunotherapies could be promising approaches based on preliminary results.

The recent availability of targeted anti-TRK therapies represents a new opportunity to treat patients with advanced cancers harboring NTRK gene fusions. In this article, we present an update on the practical modalities of implementing a "NTRK testing" to search for these fusions in view of the performances and availability of the different testing methods and the epidemiological characteristics of the tumors liable to present the NTRK1, NTRK2 or NTRK3 gene fusions.

Breast MRI is used as a reference for screening breast cancer among women with a genetic high risk. Its sensitivity and specificity might decrease because of the background parenchymal enhancement. Therefore, it is recommended to plan the MRI between the 7th and the 14th day of the menstrual cycle despite of the burden of this organization. Our aim was to evaluate the interpretation (performance) of the MRI performance when it was done out of this period.

While rare compared to extra-cranial neoplasms, glial and glioneuronal tumors are responsible of high morbidity and mortality. In 2016, the World Health Organization introduced histo-molecular ("integrated") diagnostics for central nervous system tumors based on morphology, immunohistochemistry and the presence of key genetic alterations. This combined phenotypic-genotypic classification allows for a more objective diagnostic of brain tumors. The implementation of such a classification in daily practice requires immunohistochemical surrogates to detect common genetic alterations and sometimes expensive and not widely available molecular biology techniques. The first step in brain tumor diagnostics is to inquire about the clinical picture and the imaging findings. When dealing with a glial tumor, the pathologist needs to assess its nature, infiltrative or circumscribed. If the tumor is infiltrative, IDH1/2 genes (prognostic marker) and chromosomes 1p/19q (diagnosis of oligodendroglioma) need to be assessed. If the tumor appears circumscribed, the pathologist should look for a neuronal component associated with the glial component (glioneuronal tumor). A limited immunohistochemistry panel will help distinguish between diffuse glioma (IDH1-R132H, ATRX, p53) and circumscribed glial/glioneuronal tumor (CD34, neuronal markers, BRAF-V600E), and some antibodies may reliably detect genetic alterations (IDH1-R132H, BRAF-V600E and H3-K27M mutations). Chromosomal imbalances (1p/19q codeletion in oligodendroglioma; chromosome 7 gain/chromosome 10 loss and EGFR amplification in glioblastoma) and gene rearrangements (BRAF fusion, FGFR1 fusion) will be identified by molecular biology techniques. The up-coming edition of the WHO classification of the central nervous system tumors will rely more heavily on molecular alterations to accurately diagnose and treat brain tumors.

The innate immune response is nonspecific and constitutes the first line of defense against infections by pathogens, mainly by enabling their elimination by phagocytosis or apoptosis. In immune cells, this response is characterized, amongst others, by the synthesis of restriction factors, a class of proteins whose role is to inhibit viral replication. Among them, the proteins of the APOBEC3 (Apolipoprotein B mRNA-editing Enzyme Catalytic polypeptide-like 3 or A3) family are major antiviral factors that target a wide range of viruses. One of their targets is the Human Immunodeficiency Virus Type 1 (HIV-1): the deaminase activity of some A3 proteins converts a fraction of cytidines of the viral genome into uridines, impairing its expression. Nevertheless, HIV-1 counteracts A3 proteins thanks to its Vif protein, which inhibits them by hijacking several cellular mechanisms. Besides, APOBEC3 proteins help maintaining the genome integrity by inhibiting retroelements but they also contribute to carcinogenesis, as it is the case for A3A and A3B, two major factors in this process. The large range of A3 activities, combined with recent studies showing their implication in the regulation of emerging viruses (Zika, SARS-CoV-2), allow A3 and their viral partners to be considered as therapeutic areas.