The diagnosis of chronic myeloid leukemia is based on the presence of translocation t(9,22). Additional cytogenetic abnormalities may exist at diagnosis and have prognostic value. The authors evaluated the relationship between these additional chromosomal abnormalities, clinical presentation, and therapeutic response.

Recent progres in massive deep sequencing have paved the way to routine exploration of the current panorama of inherited predisposition to breast cancer, through multigene panel analysis. Cancer risks and spectrum vary according to the gene at stake. Surveillance modalities are thus adapted to the risk-level : (1) very high, which follow specific recommendations from french NCI (INCa) ; (2) high and (3) moderate ; in the latter case, patients'follow-up compares to women of the general population. In the absence of causal mutation, other risk factors may be considered and professional scores be calculated. Of note and according to french HAS recommendations issued in 2014, the family history prevails ; on this basis, INCa has set up a national coverage of follow-up networks which specifically address high risk individuals, with or without mutation. Finally, an innovative path of specific targeted-therapies is currently opening for mutation carriers.

Biology flourished during the XXth century and was profoundly disrupted during the last decade because of the transition to the post-genomic era, the spread of high-throughput biology, and the advent of a relatively new discipline, namely bioinformatics. This latter, which encompasses the collection, organization and analysis of biological data using the computer tool, has quickly become inseparable from the studies related to the genome understanding. The consequences of the different mutations that may affect our genes are responsible for a change in the protein sequence and are likely to affect, for example, the stability of the protein, its intracellular targeting, its maturation, its assembly in a multimeric structure, the essential sites for its enzymatic activity or for the interaction with ligands. Thus, a number of bioinformatic developments have made it possible to set up in silico prediction tools of the structure of a protein that is aiming at predicting the impact of local mutations on the structure of proteins. Throughout our study, we have been interested in exploring, through in silico bioinformatic study, three analytical, prediction and modeling, software, choosing as exemple the G12D mutation that affects the proto-oncogene KRAS found in numerous algerian patients with bronchopulmonary cancers cells (NSCLC). This study allowed us to integrate these bioinformatic tools into our laboratory of developmental biology and LBDD differentiation at the University of Oran 1 Ahmed Benbella, in Algeria. Thus, we have been able to conclude, even if the found mutation is predicted to be tolerated and has no deleterious effect on the entire Ras protein, that the consequence of this missense mutation depends mainly on the position in the protein and the chemical properties of the amino acid involved in the substitution and which shows a strong affinity with the GTP molecule.

Lung cancer is the most diagnosed and deathly type of cancer worldwide. It has a poor prognosis because of a late diagnosis, high metastatic potential and resistance to conventional therapies. Since the 2000s, the emergence of targeted therapies has improved patients' outcomes. However, these therapies concern only a small proportion of patients, selected by the presence of molecular biomarkers that indicate the targeting relevance. Here, we discuss the possibility that new phenotypical biomarkers could be predictive factors for targeted therapies in lung cancer.

Many types of genodermatosis exist, with numerous modes of transmission. The development of molecular genetic methods, in particular the most recent sequencing techniques, can be used to identify an increasing number of genes involved in these forms of genodermatosis while providing confirmation or more details regarding clinical diagnosis. Thanks to this approach, it is possible to determine risk of recurrence and to formulate an antenatal strategy. These technologies have led to improved molecular definition and to a better understanding of the physiopathological mechanisms involved in different genodermatoses such as bullous epidermolysis, keratinisation disorders, pigmentation disorders, potentially tumoral conditions, and epidermal and pilar dysplasia. The large amount of information provided by high-throughput sequencing makes it possible to study modifying genes as well as genotype-phenotype correlations. However, this genetic information in its turn poses problems of interpretation and of control of the resulting data. The use of genetics in dermatology for the purposes of diagnosis or research requires a consultation to provide patients with information regarding the genetic tests involved and the potential consequences thereof for them and their families. Furthermore, with pangenomic approaches there is a higher probability of fortuitous discovery of abnormalities such as variants associated with risks predisposing to cancer or neurodegenerative disease. Collaboration between dermatologists and geneticists enables optimisation of patient management in terms of diagnosis and genetic counselling in the event of such rare diseases. Therapeutic applications are beginning to be developed. The scope of therapeutic application includes gene therapy, replacement therapy (enzyme therapy) and targeted therapy.

The giant fibrovascular polyp of the esophagus is a rare, benign and typical entity described in 1957. This lesion is easily identifiable in its macroscopic and microscopic aspects. However, recent studies question the existence of the giant fibrovascular polyp of the esophagus. The demonstration of an amplification of the MDM2 gene poses the diagnosis of well-differentiated liposarcoma. We describe here a case of an esophagus polyp in a 67-year-old man. The diagnosis of giant fibrovascular polyp of the esophagus was initially retained. Secondly, the immunohistochemical and fluorescence in situ hybridization techniques showed amplification of the MDM2 gene and reclassified the lesion to a well-differentiated liposarcoma. The search for an undifferentiated contingent is essential to not ignore a dedifferentiated liposarcoma, which is a high-grade sarcoma with a poorer prognosis.

Lynch syndrome (LS) is a hereditary predisposition to cancers, first of all, colo-rectal and endometrial cancers in women. Although recommended, gynecologic screening has never proven its benefit. Prophylactic surgery can be considered once the parental project is completed. There are few data regarding the assessment of prophylactic surgery. The objectives of our study were to evaluate the feasibility and morbidity of prophylactic hysterectomy in patients with Lynch syndrome.

We report the case of a 22-year-old patient with acute abdominopelvic pain. The diagnosis of hypercalcemic small cell carcinoma (SCCOHT)/ovarian rhabdoid tumor has been made. Small cell carcinoma of hypercalcemic type is a rare and aggressive tumor that occurs in young women. The diagnosis of this tumor and the management must be rapid in view of its aggressiveness. Through this observation, we specify the epidemiological, diagnostic, molecular aspects and discussions about its name.

Verrucous nevus is a benign tumor showing a linear pattern on Blaschko lines. It is caused by mosaic mutations of the receptor FGFR3 gene. It manifests as an aesthetic disfigurement, but individuals even experience functional complications due to itchiness. Lesions may be localized or extended (giant). In our context, the scarcity of specialized centers in dermatology is a cause of diagnostic delay inducing the patient to undertake unsuitable therapies responsible for infectious or degenerative complications. We report the case of a 15-year old girl with a history of keratotic papules showing a linear pattern along the neck, the right upper limb, the flank since childhood. Histological examination confirmed the diagnosis of verrucous nevus.

In 2016, the WHO classification of testicular germ cell tumors was revised considering advances in the understanding of their tumorigenesis and molecular features. This restructuring led to a division into two major groups with, on one hand, prepubertal-type tumors, not derived from germ cell neoplasia in situ (GCNIS), and on the other hand, postpubertal-type tumors, GCNIS-derived, which occur in youg men (seminoma and non seminomatous germ cell tumors - embryonal carcinoma, yolk sac tumor, teratoma and choriocarcinoma essentially). The term germ cell neoplasia in situ is consensually accepted as a new terminology for the precursor lesion. In this new classification, the term "spermatocytic seminoma" is replaced by "spermatocytic tumor", reclassified among non-GCNIS-derived tumors. The purpose of this change of nomenclature is to reflect the usually non-aggressive behaviour of this tumor and to avoid any confusion with usual seminoma. The spectrum of trophoblastic tumors continues to expand with the description of new rare entities such as the cystic trophoblastic tumor, the placental site trophoblastic tumor and the epithelioid trophoblastic tumor. This review aims to provide a focus on testicular germ cell tumors highlighting the new immunohistochemical and molecular features responsible for the restructuring of classification. The TNM staging is presented according to the AJCC 8th edition 2017 update.

Hereditary diffuse gastric cancer is a form of gastric cancer associated, in about 40 % of cases, with a germline mutation of the CDH1 gene. The management of patients with a pathogenic mutation of this gene is based on total prophylactic gastrectomy because, until proven otherwise, endoscopic monitoring is insufficient. We report a series of eight patients with pathogenic CDH1 mutation who underwent total prophylactic gastrectomy in our centre.

This chapter focuses on the most recent advantages in the medical treatment of localized pancreatic cancer.

The sarcomatoid variant of renal cell carcinoma is a highly aggressive tumor with propensity for metastasis and limited therapeutic options. Metastases of sarcomatoid renal cell carcinoma can sometimes be mistaken for a variety of spindle cell sarcomas, particularly at soft tissue sites in the absence of a history of a kidney tumor. Immunoreactivity for markers associated with certain types of soft tissue sarcomas can, therefore, pose a pitfall for diagnosis under such circumstances. We evaluated the immunohistochemical and molecular features of 49 cases of sarcomatoid renal cell carcinoma with special emphasis on the expression of MDM2 by immunohistochemistry and MDM2 amplification by fluorescence in situ hybridization. Of the 49 sarcomatoid renal cell carcinoma cases evaluated by fluorescence in situ hybridization, 5 (10%) were positive for MDM2 gene amplification and 5 (10%) contained polysomy 12. Immunohistochemical nuclear expression for MDM2 was also observed in 30/49 (61%) cases; of these, 15/19 (78%) were metastatic and 15/30 (50%) were primary. MDM2 expression by immunohistochemistry has been previously reported in conventional clear cell renal cell carcinoma; however, occurrence of this phenomenon has not yet been properly assessed in the sarcomatoid variant of renal cell carcinoma. Our study demonstrates that alterations of the MDM2 pathway are relatively frequent in sarcomatoid renal cell carcinoma, and nuclear positivity for MDM2 by immunohistochemistry, as well as MDM2 amplification by fluorescence in situ hybridization may pose a potential pitfall for diagnosis with dedifferentiated liposarcoma at metastatic sites. A panel approach to immunohistochemical testing is recommended for the diagnosis of these lesions. Also, identification of cases of sarcomatoid renal cell carcinomas harboring MDM2 copy number gain or gene amplification may also have potential therapeutic implications.

Meningeal melanocytic tumors are rare. We report an exceptional case of transformation of a meningeal melanocytoma in a malignant melanoma. The course of the disease extents from 61-years to 85-years and ends with the death of the patient. Besides histopathological and immunohistochemical data, we also report the array CGH study of the melanocytoma and melanoma components suggesting the malignant transformation from whole chromosome gains in the melanocytoma to additional segmental aberrations in the malignant melanoma. Beyond the rarity of this tumor subtype, this case report highlights the potential interest of molecular analyses for diagnostic and prognostic purposes in the field of meningeal melanocytic tumors.

Careful sequencing studies on small samples of normal oesophageal epithelium reveal the presence of very abundant cellular clones harbouring mutations in known cancer genes (and elsewhere). The number and size of these clones increases with age. This surprising finding confirms previous studies on sun-exposed epidermis. It has important implications for the understanding of cancer initiation and will hopefully lead to conceptual and clinical advances.