The main objective of oncogenetics is to characterize a subpopulation of patients at high risk of cancer development at an early age in order to provide specific recommendations for an optimized follow-up and care path. Oncogenetic counselling helps to assess individual risk from a family history. By a family approach of formal genetics, the key issue is to identify families with a strong aggregation of cancers, and, in particular, suggesting a specific syndrome of inherited predisposition to cancer. This approach can lead to the proposal of germline genetic testing in search of causal mutations. As up to know, the search for a constitutional mutation in the BRCA genes has led to the identification of a causal deleterious mutation in less than 10% of index-cases analyzed. It is therefore important to evaluate the impact of new genes in the current panorama of inherited predisposition to breast and ovarian cancer.

The lymphatic system is made up of vessels that drain interstitial fluids throughout the body. The circulation of the lymph (liquid in the lymphatic system) in the lymphatic vessels is unidirectional: tissues to the lymph nodes and then to the veins. Ganglia are mechanical filters but also immune barriers that can block the progression of certain pathogens as well as cancer cells. However, most studies on the lymphatic system and cancer highlight the role of the lymphatic network in metastatic dissemination as tumor cells use this network to reach other organs. However, recent studies describe a beneficial role of the lymphatic system and of the vascular endothelial growth factor C (VEGF-C) which is one of the main factors responsible for the development of lymphatic vessels in cancer. In this review, we will illustrate this ambivalent and emerging role of VEGF-C and the lymphatic system in cancer aggressiveness.

Gynaecological cancers are frequent, with more than 16,000 cases per year in France for 6500 deaths. Few improvements in diagnostic methods, prognostic tools, and therapeutic strategies have occurred in the last two decades. Tumour genomic analyses from, at least in part, the Cancer Genome Atlas have identified some of the molecular alterations involved in gynaecological tumours growth and spreading. However, these data remain incomplete and have not led to dramatic changes in the clinical management of our patients. Moreover, they require invasive samples that are not suitable to objectives like screening/early diagnosis, assessment of treatment efficacy, monitoring of residual disease or early diagnosis of relapse. In the last years, the analysis of circulating tumour biomarkers (also called "liquid biopsies") based on tumour cells (circulating tumour cells) or tumour nucleotides (circulating DNA or RNA) has been massively explored through various indications, platforms, objectives; data related to circulating tumour DNA being the most important in terms of number of publications and interest for clinical practice. This review aims to describe the methods of analysis as well as the observations from the analysis of circulating tumour DNA in gynaecological tumours, from screening/early diagnosis to the adaptation of treatment for advanced stages, through choice of treatments and monitoring of subclinical disease.

Mucosal melanoma is a rare malignant disease developed from melanocyte. We report the case of a patient with nasal cavity mucosal melanoma with a primary clinical and histological diagnosis of malignant lentigo with mucosal spreading. The presence of a c-Kit mutation, in a second lecture and the evolving nature of the lesion, reorientated the diagnosis of malignant lentigo to mucosal melanoma with skin extension. Extensive surgical resection and foramen free flap with costal graft reconstruction may have a local control of the disease. Yet, after one year, a regional evolution involving a parapharyngeal node was treated by stereotaxic radiotherapy. After 5 years, the patient was considered in clinical and radiological remission. Malignant lentigo with mucosal extension is a very rare situation, this diagnoses must be evoqued after setting mucosal melanoma diagnosis.

Checkpoints inhibitors are known to induce striking tumor responses in advanced MSI colorectal cancers, which used to be related to a poor clinical outcome. The incidence of the MSI phenotype is highly heterogeneous across non-colorectal cancers. The highest incidence rates are found in endometrioid forms of uterine cancers and in gastric tumors (20 to 40 % and 10 to 33 %, respectively). The association between a "MSI" tumor phenotype and other clinical or biological tumor characteristics is still under debate. Its prognostic value has not been determined yet. The deficiency of the DNA mismatch repair (dMMR) system of such tumor cells increases their mutational load and induces the production of so-called neo-antigens. Therefore, checkpoint inhibitors are a target therapeutic class for this molecular group of tumors. For example, response rates reach more than 50 % in pre-treated advanced endometrial cancers and in metastatic gastric tumors in association with a first line of chemotherapy. Those promising results imply the development of reliable biomarkers predictive of tumor response to immunotherapy. The present article summarizes the clinical outcomes related to the administration of checkpoint inhibitors in non-colorectal cancers. The ongoing clinical trials of such therapeutic class in this patient population are displayed.

Among the different promising predictive biomarkers in immuno-oncology, the tumor mutational burden (TMB) may soon impose itself in clinical routine practice, in association with PD-L1 immunohistochemistry testing. However, the TMB is used currently in clinical trials only, in particular in the thoracic oncology field. If this biomarker becomes mandatory in the near future, the pathologist will have to respond to new challenges in tight collaboration with the activity of molecular pathology platforms. Given the high incidence of lung cancer in France, this new development could have a strong impact on the daily life of the laboratories. This review addresses the different challenges which could be soon proposed to the laboratories and the pathologists due to the use of TMB assays on a daily practice.

The identification of ALK and ROS1 rearrangements has become essential for the theranostic management of patients with non-small cell lung cancer, especially in stage IV or inoperable patients. These testings are now performed by immunohistochemistry on histological samples and confirmed by fluorescent in situ hybridization in case of positive or doubtful results. The diagnosis of lung cancer is often performed at an advanced or metastatic stage and cytological sample could be the only material containing malignant cells available at these stages. Therefore, the detection of ALK and ROS1 rearrangement by immunocytochemical analysis on cytological specimens is needed. We performed this test on 27 cytological samples of lung adenocarcinomas, and we compared our results with several other techniques: on the same sample or on biopsy in another laboratory, on the same sample by fluorescent in situ hybridization and/or immunochemistry. We found a very good concordance between all these techniques, thus validating our immunocytochemical method on cytological samples according to the ISO 15189 norm.

Malignant mesothelioma is a rare tumour, usually the result of asbestos exposure. Several cases of familial aggregation have been reported and recently shown to be associated with constitutional mutations of the BAP1 gene. BAP1 is a deubiquitinating enzyme implicated in several different cellular mechanisms such as the repair or differentiation of DNA. About a half of malignant mesotheliomas present a somatic, bi-allelic inactivation of BAP1, demonstrated by nuclear extinction on histochemistry. Constitutional alterations of BAP1 are extremely rare. Present in the heterozygous state they are transmitted as an autosomal dominant. They are associated with a risk of developing other tumours such as uveal and cutaneous melanomas, benign melanocytic tumours (melanocytic BAP1-mutated atypical intradermal tumour or MBAITS) and clear cell renal carcinomas. The causal link between mesothelioma and germinal mutations of BAP1 has still not been clearly identified. At present there is, in France, no consensus on recommendations for the management of patients with these mutations. This article is a synthesis of the literature on the functions of the BAP1 gene, the tumour risks related to its alteration and the follow up of patients bearing a constitutional mutation.

Next generation immunotherapies have limited efficacy in colorectal cancer. Immune checkpoints inhibitors demonstrated their benefit in mismatch repair-deficient tumors, which also exhibit microsatellite instability (MSI). The Consensual Molecular Subtype (CMS) classification has been recently proposed and highlights specific immune escape mechanisms for each subtype. CMS1 "immune" subtype is hypermutated with a favorable immune microenvironment for immune checkpoints inhibitors activity. Importantly, CMS1 is not restricted to MSI tumors and includes also exonucleasic domain POLE mutated tumors which are good candidates for immunotherapy. The scope of this comprehensive review is to described immune anomalies and propose immunomodulating strategies for each CMS subtype in colorectal cancer. Finally, the potential interest of tumor mutation burden and the Immunoscore® in colorectal cancer is discussed taking into account the molecular classification and obstacles to antitumoral immune activity.

Information on risk levels is an essential part of the prevention of colorectal cancer (CRC). The objective of this article is to describe a tailored intervention carried out to inform the protagonists about the high risk of CRC due to family history and then to understand, through an interdisciplinary analysis, the mechanisms implemented during the intervention.

PREDICTIVE BIOMARKERS OF RESPONSE TO IMMUNE CHECKPOINT INHIBITORS: PD-1 checkpoint inhibitors are becoming the reference treatment for several types of cancers. Many patients show remarkable efficacy and low toxicity. However, some patients have a better outcome than others with PD-1 checkpoint inhibitors. So, it is crucial to identify biomarkers of response. We review here the available data of several potential biomarkers of efficacy. The expression of PD-L1, detected by immunohistochemistry on tumor cells and immune cells is a good predictive biomarker of response for some cancers; however, this method is not standardized, and there are different antibodies, different cut-off values, and different targets (tumor or microenvironment). Moreover, the expression of PD-L1 is dynamic and heterogeneous within the tumor: expression is discordant between primary tumor and metastasis or between biopsy and surgical specimen. Peripheral blood lymphocytes also can be informative, especially the baseline neutrophil to lymphocyte ratio which is easy to measure in daily practice. High rate of neoantigens is also associated with improved response. Therefore, mutation burden can be predictive of response and this explains why tumors with microsatellites instability have an enhanced response. Similarly, genetic signatures are linked with resistance or response to treatment. Gut microbiota is associated with improved antitumor immune response although the underlying mechanism is not well understood so far. Lastly, it seems that cytokines, mediators of immunity may play a role in the response to immunotherapy and so, constitute an interesting biomarker. Several potential biomarkers are identified but none is prospectively validated so far.

A traditional lecture given during the annual meeting of the French Society of Dermatology in Paris summarizes the highlights of the scientific literature over the past year. In the current article the selection of the 2017-2018 period retains the following areas of interest: role of microbiome in the response to anti-PD-1 and in autoimmunity, PI3Kδ inhibitors in autoimmune bullous diseases, diagnostic and therapeutic applications of CRISPR/Cas, arrival of CAR-T cells therapy into clinical practice, gene therapy successes, use of targeted therapies in genodermatoses and integration of genetics in primary care. © 2018 Elsevier Masson SAS. All rights reserved.

This study aims to describe the different bcr-abl gene transcript variants in order to determine their frequency and to study their influence on CBC diagnostic test. We conducted a cross-sectional study of 34 patients with chronic myeloid leukemia in Togo. The search for fusion transcripts was performed in the laboratory of biological haematology at the Henri Mondor Hospital, Créteil (France). The average age of patients was 42,32±14,87 years ranging between 9 and 65 years. Most patients were male, with a sex- ratio of 1.61 (21 men and 13 women). Molecular examination showed b3-a2 transcript and b2-a2 transcript. Nineteen patients (55.88%) expressed b3-a2 transcript, 13 patients (38.24%) b2-a2 transcript (32.10%) and two patients expressed both b3-a2 and b2-a2 transcripts (5.88%). At diagnosis, mean hemoglobin level, the average number of white blood cells and the average number of platelets in patients expressing b3-a2 transcript were 99,2g/L; 207,63g/l and 451,28g/l respectively. In patients expressing b2-a2 transcript values were 104,6g/l, 114,32g/l and 486,11g/l. In patients with both transcripts, values were 67g/L, 867g/l and 780g/l respectively. CBC parameters are more significantly altered in patients with both transcripts b3-a2 and b2-a2.

Metastasis in cancer patients is often associated with a poor prognosis. However, we still have limited knowledge of the underlying molecular mechanisms, due to the great complexity of the biological processes involved in the formation of metastases. During tumor progression, the metastatic cells acquire genetic and epigenetic modifications allowing them to adapt to the various environments they will encounter (in the circulation and the host microenvironment) and to resist to the antitumor therapeutic agents. In this review, we expose the current knowledge on the biology of metastases. We summarize the different signaling pathways involved in the successive steps of the metastatic cascade, highlighting recent advances in the field to better understand the molecular mechanisms leading to metastasis formation. In addition, our understanding of metastatic progression has made great progress with the recent advances in high throughput sequencing techniques. We expose data from genomic analyzes of metastases. These studies allowed the identification of alterations acquired exclusively in distant metastases. They highlight the emergence of alterations offering new targeted therapeutic options for cancer patients and they provide new insight into the mechanisms of treatment resistance at the origin of metastatic relapses. Finally, we present latest clinical trials based on the genomic profiles of metastases, initiated in recent years, and we discuss their potential impact in personalized medicine.