Targeted therapy in lung cancer changes the prognostic and treatment of patients. MET is an oncogene including exon 14 mutations and gene amplification associated with worse prognosis. We here report the case of a 47-year-old former smoker, woman, with a stage IV lung adenocarcinoma with multiple chemotherapy failure. A MET amplification was identified and the patient consequently received crizotinib. A major response was observed after eight weeks of treatment. MET amplification screening appears to be interesting with some oncogenic-addicted tumor response rate. Those patients should be enrolled in clinical trials dedicated to tumor with MET alteration.

Among patients with non-small-cell lung cancer, coexistence of EGFR mutation and ALK rearrangement is rare. We describe the clinical features of two patients with this double anomaly.

Lynch syndrome or hereditary nonpolyposis colorectal cancer (HNPCC) is the most common form of hereditary colorectal cancers. It increases cancer susceptibility, the risk of colorectal cancer in first-degree, endometrial cancer in women, and to a lesser extent, other cancers (ovarian, small bowel, stomach, urinary tract and hepatobiliary). Thus, the cumulative risk of developing colorectal cancer or endometrial cancer at the age of 80 years rises to 20 and 40% respectively. These cancers are characterized by a positive family history, their occurrence at an early age, and by the development of metachronous cancers in the same individual. This syndrome is transmitted in an autosomal dominant manner. The genes whose alteration is associated with the presence of an HNPCC belong to the family of DNA mismatch repair genes (DNA mismatch repair or MMR): MSH2, MLH1, and MSH6 are involved, in decreasing order of frequency, in 35%, 25% and 2% of cases respectively. Colonoscopic and gynecological monitoring is recommended for patients with a constitutional mutation in MSH2, MLH1 or Msh6 genes. We report one of the first moroccan case with Lynch syndrome whose constitutional mutation in the MLH1 gene was identified in a family member with colon cancer. In reply to the inquiry ofother healthy family members, a presymptomatic diagnosis was made allowing to formulate an appropriate monitoring strategy. Our study aims to highlight the role of oncogenetics in the management of patients with cancer and their families.

NEOADJUVANT CHEMOTHERAPY IN HER2-POSITIVE AND TRIPLE-NEGATIVE BREAST CANCER: Neoadjuvant chemotherapy is a standard option in the management of operable breast cancer, as effective as adjuvant chemotherapy in term of survival and with the potential to increase the rate of breast conservation. In HER2+ and triple-negative breast cancers, neoadjuvant chemotherapy is associated with a high probability of pathological complete response, which strongly predicts survival outcome. In HER2+ breast cancer, trastuzumab, in combination with neoadjuvant chemotherapy, mostly anthracyclines and taxane-based, demonstrated a significant increase in pathological complete response rate. Recently, dual HER2 blockade strategies (lapatinib-trastuzumab or pertuzumab-trastuzumab) demonstrated a significant improvement in terms of pathological complete response over trastuzumab. In triple-negative breast cancer, recent data indicate that incorporating platinum compounds to neoadjuvant chemotherapy also significantly improves this parameter. Yet, in both subtypes, whether these substantial improvements may lead to significant benefits in terms of survival and breast conserving surgery remains to be demonstrated.

EXAMPLE OF SARCOMAS IN FRANCE: Sarcomas are rare and heterogeneous tumours, and improvement of knowledge and of patient management need to gather and share data and biological material. The French sarcoma database stores in a warehouse clinical, pathological, molecular, therapeutic and follow-up data as well as data on samples and medical practices. This database and the national structured networks constitute major tools for the French Sarcoma Group.

WHY PATHOLOGY REMAINS (AND WILL REMAIN) MANDATORY?: Numerous techniques are now available for the molecular evaluation of a tissular or cellular sample in the context of metastatic disease. They include in situ molecular techniques, such as immunohistochemistry for the study of proteins and peptides, in situ hybridization for the study of nucleic acids and in situ cytogenetics (FISH and its variants) for the demonstration of chromosome alterations. They also include all the techniques of molecular biology, which can now be applied to frozen as well as fixed tissue samples. The combination of all these techniques makes it possible an integrated and coherent approach, not limited to the description of DNA abnormalities, but able to correlate genomic alterations with functional, and even structural changes. A second major interest of the analysis of tissue samples is that they make it possible to analyzing not only tumor cells, but also their environment, formed by the stroma and its populations. The study of stroma and of stromal cells, in particular of immune cells, is now of paramount importance for providing new prognostic and predictive biomarkers, especially for anti-angiogenic strategies and for cancer immunotherapy. Tissue analysis is therefore the only way to perform a « total », « phenogenomic » characterization of the tumor as an organ : this is particularly important in the moment in which descriptive genomics is substituted by functional genomics and integrated biology.

Oligometastic progression (or solitary metastases) can justify ablative treatment for metastatic treatment. When such a strategy is discussed, it is important to notice that definition of oligometastases is not consensual both in terms of clinical presentation than on the biological basis. Does a specific biological background truly exist and are there markers that could predict for additional occult disease and its oligo or polymetastatic profile in individuals with demonstrated oligometastasis. This article provides a summary of the state of the art in this field and highlights some current areas of controversies.

To evaluate in a high volume center the practice and the performance of cancer genetic screening for patients with multiple renal tumors without a predisposition to kidney tumors known at the time of surgery.

While mutations in BRCA1 and BRCA2 are found in only a minority of breast cancer patients, their impact for those patients is important. It is a powerful risk factor for this disease with respectively 65% and 45% of the women developing breast cancer. It requires a specific screening program starting at age of 25 that includes magnetic resonance imaging and risk reduction measures such as bilateral mastectomy and oophorectomy can be proposed. The psychological impacts of the mutation and its implications are not negligible. The testimony of Angelina Jolie in 2013 certainly contributed to public awareness and helped the affected women to cope better with the situation. Cancer treatments are also influenced by detection of a mutation with an increased role for platinum derivatives and the recently developed specific therapies, such as PARP inhibitors.

Approximately 5 to 10% of all malignant tumors can be attributed to highly penetrant cancer predisposition genes. More than 100 of these genes have been identified. Taking into account the complexity and the various implications of predictive oncology, and in accordance with the current regulation, every constitutional molecular analysis must be performed within the framework of a genetic counseling. Besides the implementation of the next generation sequencing technology in clinical laboratory, family history remains a key information to identify hereditary cancer syndromes and to propose genetic counseling. New challenge areas for clinicians involved in predictive oncology are also associated with this technical revolution.

Since the recent evidence of a tubal origin of most ovarian cancers, opportunistic salpingectomy could be discussed as a prophylactic strategy in the general population and with hereditary predisposition. We aimed to survey French gynecological surgeons about their current surgical practice of prophylactic salpingectomy.

Oncogenetics is the medical care of families with hereditary cancer risk. Bioethics laws strictly control this activity. Taking into account the medical benefit and lives saved through oncogenetics when a constitutional mutation in hereditary cancer risk gene is found, the law requires that information is disseminated to the relatives. If the consultant cannot or will not provide this information, this is the geneticist who will contact the family. This is an unprecedented situation where the doctor encourages medical advices not requested by patients. The Clermont experience is shown on the application of the law and its practical difficulties. Currently the technology of molecular genetic diagnosis is changing rapidly and allows new diagnostics whether at the level of cancerous tumors or in the genome with the perspective that everyone can soon have the sequence of the entire genome with the interpretation of personal risk of cancer diseases or other kinds. It is necessary to better anticipate emerging ethical issues already raised by the first medical practices of these technologies.

This review reports 3 of recently published molecular classifications of the 3 main gastro-intestinal cancers: gastric, pancreatic and colorectal adenocarcinoma. In colorectal adenocarcinoma, 6 independent classifications were combined to finally hold 4 molecular sub-groups, Consensus Molecular Subtypes (CMS 1-4), linked to various clinical, molecular and survival data. CMS1 (14% MSI with immune activation); CMS2 (37%: canonical with epithelial differentiation and activation of the WNT/MYC pathway); CMS3 (13% metabolic with epithelial differentiation and RAS mutation); CMS4 (23%: mesenchymal with activation of TGFβ pathway and angiogenesis with stromal invasion). In gastric adenocarcinoma, 4 groups were established: subtype "EBV" (9%, high frequency of PIK3CA mutations, hypermetylation and amplification of JAK2, PD-L1 and PD-L2), subtype "MSI" (22%, high rate of mutation), subtype "genomically stable tumor" (20%, diffuse histology type and mutations of RAS and genes encoding integrins and adhesion proteins including CDH1) and subtype "tumors with chromosomal instability" (50%, intestinal type, aneuploidy and receptor tyrosine kinase amplification). In pancreatic adenocarcinomas, a classification in four sub-groups has been proposed, stable subtype (20%, aneuploidy), locally rearranged subtype (30%, focal event on one or two chromosoms), scattered subtype (36%,<200 structural variation events), and unstable subtype (14%,>200 structural variation events, defects in DNA maintenance). Although currently away from the care of patients, these classifications open the way to "à la carte" treatment depending on molecular biology.