Afatinib (BIBW 2992) is an irreversible multi-target HER receptor tyrosine kinase inhibitor developed in patients with advanced solid tumours. Several phase I studies were conducted in patients with non-small cell lung cancer (NSCLC), as a single agent or in combination. In further phase II or III studies, patients were selected based on the duration of response to first generation EGFR-TKI in previous line (supposed to have greater chance to have an activating EGFR mutation) or based directly on the EGFR activating mutation status. Here, we report and comment the main results of these studies in lung cancer patients. This drug has been approved by the Food and Drug Administration in June 2013 for the first-line treatment of patients with metastatic NSCLC whose tumours have EGFR mutation. In Europe, it has been approved in September 2013 in the same indication.

We report here the case of a sixty-eight-year old woman with chronic myeloid leukemia. Molecular techniques identified the presence of the rare e19a2 BCR-ABL1 transcript. The patient was treated by 1(st) generation tyrosine-kinase inhibitor (TKI) (imatinib). Disease monitoring was performed by cytogenetic analyses and quantification of the BCR-ABL1 transcript. After 3 months, the treatment was modified due to an absence of biological response and poor tolerance. After 21 months with 2nd generation TKIs (nilotinib), the patient was responding optimally to treatment, with a complete cytogenetic response and a major molecular response. This observation emphasizes the importance of determining the chromosomal breakpoints at diagnosis to enable adequate molecular monitoring of residual disease. Careful monitoring of minimal residual disease is important to thoroughly assess the response to treatment, detect resistance and adapt the therapeutic strategy. The kinetics and the depth of the response to TKI also represent major prognostic factors. Molecular monitoring is performed using real-time quantitative PCR, which has to be adapted to each type of transcript. For rare BCR-ABL1 transcripts, an international standardization, as it is developed for conventional transcripts, is lacking. Yet, such a harmonization would be useful to assess in an optimal and large scale way the response to TKI in these patients, and to determine what the best management is.

Nasopharyngeal carcinoma (NPC) is a complex multifactorial disorder involving both genetic and environmental factors. Genetic predisposition linked to the immune system has been associated with various tumors. This involves genetic diversity of the genes encoding the molecules of the immune response such as inflammation and anti-tumor surveillance. In this work, we examined the impact of the immunogenetic diversity on the risk of the NPC in different populations studied. These data show that the interindividual variability of the genetic regulation of immune processes increases the risk of NPC in individuals previously predisposed due to other risk factors (genetic / environmental). This synthesis, in addition to the predictive aspects, could provide innovative research for the development of new therapeutic approaches.

Exosomes are small vesicles derived from endosomes and carrying several constituants of the cell; if captured by other neighbour cell types, they can trigger novel functions in these cells. We illustrate here (through recently published results) how exosomes released by activated tumor-associated fibroblasts are able to induce in cancer cells a signalling pathway key to the acquisition of motility and hence metastatic property.

Progress in genomics with, in particular, high throughput next generation sequencing is revolutionizing oncology. The impact of these techniques is seen on the one hand the identification of germline mutations that predispose to a given type of cancer, allowing for a personalized care of patients or healthy carriers and, on the other hand, the characterization of all acquired somatic mutation of the tumor cell, opening the door to personalized treatment targeting the driver oncogenes. In both cases, next generation sequencing techniques allow a global approach whereby the integrality of the genome mutations is analyzed and correlated with the clinical data. The benefits on the quality of care delivered to our patients are extremely impressive.

Retinoblastoma is the most common intraocular malignancy of infancy with an incidence of 1/15,000 to 1/20,000 births. Sixty percent of retinoblastomas are unilateral, with a median age at diagnosis of two years, and in most cases are not hereditary. Retinoblastoma is bilateral in 40% of cases, with an earlier median age at diagnosis of one year. All bilateral and multifocal unilateral forms are hereditary and are part of a genetic cancer predisposition syndrome. All children with a bilateral or familial form, and 10 to 15% of children with an unilateral form, constitutionally carry an RB1 gene mutation. The two most frequent symptoms revealing retinoblastoma are leukocoria and strabismus. Diagnosis is made by fundoscopy, with ultrasound and magnetic resonance imaging (MRI) contributing both to diagnosis and assessment of the extension of the disease. Treatment of patients with retinoblastoma must take into account the various aspects of the disease (unilateral/bilateral, size, localization…), the risk to vision and the possible hereditary nature of the disease. The main prognostic aspects are still premature detection and adapted coverage by a multi-disciplinary specialized team. Enucleation is still often necessary in unilateral disease; the decision for adjuvant treatment is taken according to the histological risk factors. The most important recent therapeutic advances concern the conservative treatment which is proposed for at least one of the two eyes in most bilateral cases: laser alone or in combination with chemotherapy, cryotherapy or brachytherapy. Recently, the development of new conservative techniques of treatment, such as intra-arterial selective chemotherapy perfusion, aims at preserving visual function in these children and decreasing the number of enucleations and the need for external beam radiotherapy. The vital prognosis related to retinoblatoma is now excellent in industrialized countries, but long-term survival is still related to the development of secondary tumors, mainly secondary sarcoma. Retinoblastoma requires multi-disciplinary care as well as a long term specialized follow-up. Early counseling of patients and their family concerning the risk of transmission of the disease and the risk of development of secondary tumors is necessary.

Colorectal liver metastasis is one of the best-known clinical models of multidisciplinary approach. Chemotherapy, targeted therapies, surgery and interventional radiology permitted to obtain up to 40 months of survival in palliative intent for liver metastases only and between 40 to 50% of overall survival in curative intent. Genetic, epigenetic, cellular and tissular processes are more and more well described but attempts to link biological knowledge to clinical practice are still faint. The cut-off between curative and palliative intents is progressively pushed away but consequently, its signification is less clear. Maybe an additional intermediary new concept should be added, the metastatic disease chronicisation? Evaluating the patient benefice is difficult and should stand on progression free survival as surrogate marker.

Sentinel lymph node (SLN) is a concept but also a technical possibility that can be studied and applied to almost all organs with cancer. For colorectal cancer surgery, some possibilities of using the SLN are possible, other implausible and some completely new especially aware of possible analysis of SLN by a molecular biology technique. The orientation of dissection or "lymph road mapping" can be designed for this case or the surgeon may want to limit his actions, particularly in patients with a history of colonic surgical resection, to keep the digestive function in maintaining vascular axes considered not involved in the metastatic process. The use of the single analysis of SLN to determine the positive or negative status of the cleaning has failed because of the frequency of false negatives in part to the size of colic advanced cancers at diagnosis. The use of "ultra-stading" by multiple section or exhaustion of the block, can lead to reconsider a stage N0 to N1 as a point, if the analysis technique remains in HES. Unlike the "ultra-stading" by RT- PCR or immunohistochemistry was even more discussed and seems not equivalent in terms of prognosis and therefore no giving formally justification for adjuvant therapy. Currently, a new technique for molecular biology, named "OSNA", allows an analysis of all the SLN in less than 45 minutes. It is therefore possible to obtain during surgery analysis of a node with the same level of information than traditional analysis using HES. If this node is positive and if the strategy in case of positive lymph nodes was determined prior for this patient, it is possible to anticipate this strategy and place after colectomy during the same anesthesia, venous access quickly to start postoperative chemotherapy. This new technique for analyzing lymph applied to the SLN opens a new potential application of this concept in digestive oncology.

To report the relative frequency of presenting signs in Tunisian children with retinoblastoma and to evaluate their prognostic impact.

Follicular lymphoma is an indolent B-cell lymphoma. Fluctuant asymptomatic lymphadenopathies are their usual clinical manifestation. B-cell neoplasms can sometimes involve the skin. In this case, it is important to distinguish a systemic B-cell lymphoma with secondary skin involvement from primary cutaneous lymphoma. Immunohistochemical stainings and staging usually allow to make the difference. Here we report the first case of a systemic follicular lymphoma with secondary cutaneous involvement presented with papular lesions on the face mimicking a rosacea.

Juvenile myelomonocytic leukemias (JMML) are rare but severe myelodysplastic and myeloproliferative neoplasms of infancy. They represent about 10 new cases per year in France and preferentially affect males. JMML are all stem cell diseases the common denominator of which is RAS pathway dysregulation, due to mutations in RAS (NRAS, KRAS) or RAS regulatory components (PTPN11, NF1 or CBL). This leads to an hypersensivity of myeloid progenitors to GM-CSF (granulo-macrophagic colony stimulating factor) which induces in turn excessive monocytic and macrophagic proliferation in blood and bone marrow. All organs can be infiltrated by this monocytic proliferation leading to multisystemic failure. Blast crisis with transformation into acute myeloid leukemia occurs in one third of patients. A salient feature of JMML is their frequent association with predisposition syndromes such as Noonan syndrome, neurofibromatosis and CBL syndrome, which are developmental diseases associated with a constitutional RAS pathway deregulation, now grouped under the name RASopathies. Clinical heterogeneity makes JMML diagnosis difficult. Splenomagaly is the most constant sign. Palor, adenopathy, respiratory or cutaneous symptoms can also be present. Blood smear shows monocytosis (>1×10(9)/L) presence of myeloid progenitors and abnormal basophils. The demonstration of an endogeneous in vitro growth of myeloid progenitors although not very specific can help JMML diagnosis. Nowadays, genetic typing has to be included in the workup of JMML diagnosis and allows to evidence a mutation in more than 90% of cases. JMML have a poor prognosis. The only curative treatment is bone marrow transplantation but approximately 35% of patients relapse. JMML clinical course is highly heterogeneous and unpredictable. Some rare patients have an indolent evolution or even spontaneous remission. Age over two years, thrombopenia below 33×10(9)/L and high foetal hemoglobin (HbF) level for age are poor prognosis criteria but hardly predict individual outcome. Several research directions are currently being explored to improve prognosis prediction and provide more effective targeted treatments.

Small nucleolar RNAs or snoRNAs, principally implicated in post-transcriptional chemical modification of other RNAs, were among the first non-coding RNA identified, together with ribosomal and transfer RNA. Lately, snoRNA have been involved in various unexpected functions, which renewed researcher's interest for these molecules. SnoRNA processing into smaller functional RNA species (sdRNA for snoRNA-derived RNA) or into miRNA (sno-miR), snoRNA mediated regulation of messenger RNA alternative splicing or snoRNA links to human disorders, including cancers, are some of the topics developed in this review.

The recent discovery of a new kind of massive chromosomal rearrangement in different cancers, named "chromothripsis" (chromo for chromosome, thripsis for shattering) has questioned the established models for a progressive development of tumors. Indeed, this phenomenon, which is characterized by the shattering of one (or a few) chromosome segments followed by a random reassembly of the fragments generated, occurs during one unique cellular event. The same phenomenon was identified in constitutional genetics in patients with various developmental pathologies, indicating that chromothripsis also occurs at the germ cell level. Diverse situations can cause chromothripsis (radiations, telomere erosion, abortive apoptosis, etc.), and two express "repair routes" are used by the cell to chaotically reorganise the chromosomal regions concerned: non-homologous end-joining and repair by replicative stress. The in-depth analysis of the DNA sequences involved in the regions of chromothripsis leads to a better understanding of the molecular basis of chromothripsis and also helps to better apprehend its unexpected role in the development of constitutional pathologies and the progression of cancers.