Non clear cell renal cell carcinomas represent almost 20% of all renal neoplasms. Their classification is continuously being adjusted according to new cytogenetic and molecular data. Since molecular techniques are expensive, diagnosis still relies on morphological and immuno-histochemical criteria detailed hereby. Papillary renal cell carcinomas are the most important group and its classification is more and more complex. It encompasses low-grade papillary carcinomas (type 1 papillary renal cell carcinoma, oncocytic papillary renal cell carcinoma) and high-grade papillary carcinomas (type 2 papillary renal cell carcinoma, juvenile papillary carcinoma corresponding to renal carcinoma associated with Xp11.2 translocations and unclassified carcinomas). Mucinous tubular and spindle cell carcinoma and tubulocystic carcinoma are new entities, actually considered by some authors as low-grade papillary carcinomas. The so-called carcinoma of collecting ducts of Bellini and renal medullary carcinoma should be considered as intrarenal urothelial carcinoma or as high-grade papillary or unclassified carcinoma. Sarcomatoid carcinoma derives from morphological progression of any type of renal cell carcinoma. The group of oncocytomas/chromophobe renal cell carcinomas can be considered as a spectrum from benign (oncocytoma) to malignant neoplasm (chromophobe renal cell carcinoma). They are sometimes encountered in oncocytomatosis or familial Birt-Hogg-Dubbe syndrome in which tumoral cells may have hybrid features. Angiomyolipoma is usually a benign mesenchymatous neoplasm, that can be sporadic or familial (tuberous sclerosis). In the latter situation, some cases of epithelioid angiomyolipoma (potentially malignant) have been described. Renal epithelial and stromal tumors (REST) is a new concept gathering two benign mixed mesenchymal and epithelial tumors: cystic nephroma and mixed epithelial and stromal tumors (MEST).

The identification of fusion genes provides new insights into the initial mechanisms of molecular events implicated in the tumorigenesis of prostate cancer. The presence of TEMPRSS2-ETS fusion in up to half of all human prostate cancers makes it perhaps the most common genetic rearrangement in human epithelial tumors. Some data suggest that TMPRSS2-ERG fusion prostate cancers have a more aggressive phenotype which may affect cancer progression and outcome in localized tumors treated with prostatectomy. This discovery should pave the way towards future targeted therapies.

No histological or clinical criteria allow distinction between primary cutaneous marginal zone B-cell lymphoma (MZL) and secondary cutaneous forms of systemic marginal zone B-cell lymphoma. Consequently, staging alone can indicate the origin of lymphoma. Lymphoma is considered as primary cutaneous only if no other extracutaneous sites are found. We studied the histological appearance of 49 cutaneous lymphomas in order to find distinctive criteria indicative of an extracutaneous origin.

The main selected articles in pediatric dermatology covered the following topics: development and maturation of the epidermal barrier in the neonate, iatrogenic events in the neonatal ICU, diagnostic value of minor birthmarks, complications, risk factors and treatment of hemangiomas, coagulopathy in venous malformations, epidemiology and dermoscopy of congenital and acquired melanocytic nevi in childhood, growth of the body surface area, new pathogenic concepts and treatment in atopic dermatitis, the impact of filaggrin deficiency, hereditary factors in Kawasaki disease, severe and drug resistant cases, management of juvenile dermatomyositis, treatment of childhood psoriasis with biologics, the new classification of epidermolysis bullosa and therapeutic approach with cell therapy, neurological impairment in xeroderma pigmentosum, behavioural anomalies in X-linked ichthyosis, guidelines for neurofibromatosis type I, the genetics of an hereditary hypotrichosis, infantile acne, rosacea in childhood, mast cell disease management and, last but not least, treatment of hair lice with silicone.

Medical literature is rich with new and relevant information, resulting from basic or applied research. Some strong arguments are presented in this document. Firstly, the discovery and role of a virus, the polyomavirus, in the development of Merkel tumours. It is a small virus with double bit DNA strand, coding for a oncoprotein. If the polyomavirus plays a causal role in the tumorigenesis, it acts by various mechanisms. The micro-RNAs represent an abundant class of small RNA not coding for proteins, but which control the gene expression coding for proteins on a post-transcriptional level. The first obvious sign of the role of the micro-RNAs in the inflammatory dermatoses appeared recently, in particular when these micro-RNAs associated with psoriasis and atopic dermatitis were identified through a broad genomic analysis of the expression of these micro-RNAs. A new giant virus strain sheltering another unknown tiny virus to date has just been discovered. This virus infinitely small called Sputnik enables to deteriorate a much larger virus baptized Mama, at the point of preventing it to manufacture normal viral particles and also preventing it from reproducing. This discovery raises a crucial question: Is Sputnik a new system of transfer of genes of a species of one virus to another? A group of blood cells expressing E-cadherin, the dot cells, found in the fetal blood of the dermis, contributes to tissue repair through the mechanisms of cellular differentiation and their action allows healing without scar. CD4+ T helper lymphocytes producing interleukin 17 (IL17) play a pathogenic part in atopic dermatitis. The genes of the beta defensins could be involved in the genetic susceptibility of the psoriatic disease. The autoimmune origin of the alopecia areata is supported by a great number of observations, the role of neuropeptides in the initiation of the autoimmunity during alopecia areata has just been demonstrated. The dendritic cells are cells presenting antigens which play a crucial role in the adaptive immunological response. It was shown that activation of the proliferation of the lymphocytes T after the migration of dendritic cells on the level of the lymphatic ganglion depended not on Langerhans cell, but of the dendritic cell. A new way appears to control the autoimmunity in the psoriasis and involves the plasmacytoid dendritic cells which are sensitized with the DNA itself when it is coupled with an antibacterial peptide. Mast cells express cathelicidin, which acts like an antibiotic with broad spectrum and influences the defence system of the epitheliums. We have perhaps found a new therapeutic target for rosacea by disclosing high rates of cathelicidin and a series of associated proteases in skin lesions. The sebocytes express antibacterial functional peptides deriving from cathelicidin which can have a bactericidal effect against P. Acnes. A vast genomic study in the androgenetic alopecia highlighted the existence of new loci localized on the 20p11 chromosome, associated with the risk of androgenetic alopecia. New alleles to determine the color of hair and the cutaneous pigmentation were identified. Two loci (IRF 4 and SLC24A4) are highly associated with the color of hair, like three other areas. The blue color of the eyes could be due to a change of an element located in gene HERC2 preventing of the expression of OCA2. Thus, many fields of dermatology were the object of research which opens new prospects for diagnosis and treatment.

The advent and recent use of Genome-Wide Association studies (GWAS) for the search of genetic predisposition markers for prostate cancer since 2006 has put a very strong emphasis on the 8q24 locus where several single nucleotide polymorphisms (SNP) have been significantly associated with an increased relative risk. A wealth of recent papers have all confirmed the interest of this locus and identified several others. Interestingly, these markers seem to have additive effects pointing to the high complexity of prostate cancer predisposition. This situation along with our current inability to identify any causal gene(s) in these regions make these findings difficult to translate into routine clinical practice at the present time, a fortiori in terms of population screening.

We show that proliferation-related signals are omnipresent in the breast cancer transcriptome. As a result, many transcriptional signatures generated at random are valuable for the prognosis of disease-free survival: despite their biological rationale, 30-60% of published prognostic signatures are not significantly better. We propose a mathematical transformation, the super PCNA decovolution, which removes proliferation-related signals from tumours transcriptional profiles. Both random and published signatures loose nearly all their prognostic value after removal of these signals.

The majority of current major advances in the management of main human malignancies including breast, colorectum and head and neck result from the introduction of targeted therapies. An optimal application of targeted therapy needs a knowledge for the tumoral status of the target itself. It is also interesting to dispose of biological informations resulting from the interactions between treatment and target (biological proof of the concept). These informations are at the basis of the conception of new clinical protocols in oncology. In this context the role of molecular biology units is determinant. Examples of concrete applications of this strategy will be detailled particularly for the MINDACT Trial in breast cancer and for the KRAS status in the setting of EGFR targeting therapies in advanced colorectal cancer.

In this review, we will summarize the guidelines on the evaluation of anticancer medicinal products in man and definitions for genomic biomarkers (FDA validated), pharmacogenomics, pharmacogenetics, genomic data and sample coding categories.

Recent progress made in the field of sarcoma biology has shed new light on the pathophysiology of these numerous but rare diseases. Soft tissue sarcomas can be divided into 6 sub-types based on the underlying molecular biology of the disease: 1) translocation leading to fusion proteins involving transcription factors or growth factors (Ewing sarcoma, myxoid liposarcoma, dermatofibrosarcoma protuberans); 2) tyrosine kinase receptor mutations (gastrointestinal stromal tumors); 3) tumor-suppressor gene deletion (type 1 neurofibromatosis, rhabdoid tumors); 4) genetic alteration such as amplification of chromosomal regions (well differentiated/dedifferentiated liposarcoma); 5) sarcomas with more complex genetic alterations (leiomyosarcoma) and 6) abnormalities involving the cell-adhesion pathways (aggressive fibromatosis). Together with the current development of numerous targeted therapies, these recent progress are the basis of tomorrow's personalised medicine for patients with soft tissue sarcoma.

Considering both the clinical and molecular heterogeneity of breast cancers, one can easily conceive that all tumours are not equally sensitive to the different chemotherapy agents or regimens used. Thus, the identification of predictive markers of chemosensitivity should be considered as a research priority and we analyse here this question in two parts: (1) identification of predictive markers of general chemosensitivity, which means that a tumour is sensitive to any chemotherapy; (2) identification of predictive markers of specific chemotherapy which means that a tumour is sensitive to a specific cytostatic class or to a specific regimen. We will address these two aspects and will summarise ongoing trials and recently published data. These studies suggest the predictive value of biological markers either considered as single molecular markers (hormone receptors, HER2, TOPO2alpha, p53) or as multiple markers combined in so-called "signatures".

Several drugs have been developed and demonstrated similar efficacy in colorectal cancer treatment therefore with choice, time comes for decision. The biologist will have to provide the tools allowing to clarify this choice. Among the tools available, those of pharmacogenetics and pharmacogenomics appear most promising and recent examples allow to illustrate their clinical interest. The pharmacogenetics of anti-cancer agents presents a clinical characteristic, which requires to hold into account the genetic variations not only of host cells but also of those of the tumor cells. Among the most conclusive examples one is that of the prediction of severe neutropenia induced by the irinotecan among patients homozygous for * 28 allele of UGT1A1 enzyme which conjugates SN38 active compound of irinotecan, the other one is the presence of a KRAS mutated allele in tumor cell to predict resistance to anti EGFR antibodies in the treatment of colorectal metastatic cancer.

Regarding the evolution of the treatments of colorectal cancer during the last five years, it appears that numerous questions have to be considered with a strategic point of view. In order to avoid inclusion of a lot of patients in clinical patients, we urgently need the help of biology to give us arguments to choose one treatment or another. The fact that ten years after their approval, we are not able to select responders to oxaliplatin or irinotecan, confirm that this is difficult problem to solve. The contribution of biology to the prescription of drugs commonly used in colorectal cancer is discussed in this paper. There are already situations where the contribution of biology to clinical practice and prescription is not debatable : this is the case for the use of UGT1A1 status determination when using irinotecan and the determination of KRAS status for the prescription of panitumumab (and cetuximab in a few months). This individual adaptation is a dream that becomes reasonable when we look on the recent results concerning EGFR inhibitors, but a lot of work has to be done and it is not sure that biological assessment of the tumour will be able to solve all the problems. For instance, to determine predictive factors of response to angiogenesis inhibitors, it is likely that solutions will come from new techniques of imaging rather than from biology. However, new tools such as proteomics or metabolomics, as well as a better dialogue between clinician and biologist, will allow fast improvements. It must be emphasised that, for the first time in 2008, it is possible to prescribe targeted therapies to a specific "targeted" group of patients with metastatic colorectal cancer.

Oncogenesis and tumour progression are caused by the progressive accumulation of genetic and epigenetic abnormalities in pre-cancerous and cancerous cells, conferring increased capabilities of proliferation and survival. Recent technological advances, including the development of CGH arrays and high-throughput sequencing, have made it possible to map the genetic landscape of human cancers. Molecular characterisation studies have provided key insights into the disease mechanisms that can be used for the design of tailored therapies and have led to the identification of specific biomarkers for guiding patient management. Nevertheless, the genetic instability of cancer cells and the consecutive intra-tumoral heterogeneity remain critical constraints in the context of the emergence of targeted therapies.

Medulloblastoma is one of the most common malignant childhood brain tumors. It is a primitive neuroectodermal tumor (PNET) and predominantly arises in the cerebellum and 4th ventricle. Most cases of medulloblastoma are sporadic, but some predisposition syndromes are known, such as SUFU and Gorlin syndromes. Most often intracranial hypertension reveals the disease typically with headache and vomiting. However, the frequent atypical presentation should not delay neuroradiological investigations. Brain and spinal MRI can establish the diagnosis of posterior fossa tumor and define the extent of the disease. CSF study completes the staging. Histologic examination of the tumor confirms the diagnosis of medulloblastoma. Patients are classified into 2 risk groups: standard-risk medulloblastoma, defined by nonmetastatic disease treated by total or subtotal tumor resection; and high-risk patients who have disseminated disease and/or residual disease. Tumor molecular genetic findings allow the use of emerging prognostic factors and may ultimately contribute to the development of targeted therapy. Current treatment in the oldest children combines surgical resection followed by radiotherapy and chemotherapy. The aim of recent studies was to increase survival and decrease sequelae by reducing CSI in older children with standard risk medulloblastoma. Treatment in younger patients is as much as possible restricted to surgery and chemotherapy. However, long-term sequelae after treatment for medulloblastoma remain frequent and the detection and treatment of those sequelae is an essential part of the follow-up of the patients.

Familial pituitary adenomas are found in multitumoral syndromes such as multiple endocrine neoplasia type 1 (NEM1) and type 4 (NEM4) and the Carney complex (CNC); it remains at present the only known condition in the category of familial isolated pituitary adenomas (FIPA). Familial adenomas account for 3-5% of all pituitary adenomas. Their pathogenesis is known in part: mutations of the menin gene in NEM1 (80%), of the CDKN1B gene in NEM4 (several cases described), of the PRKR1A gene in CNC (50%) and the AIP gene in 15% of FIPA cases (50% of the FIPA cases with a homogeneous somatotropic phenotype). The clinical course of familial adenoma with NEM1 or FIPA is more aggressive than that of sporadic adenoma, with more macroadenomas and more patients diagnosed younger. Familial pituitary adenomas are distinguished from the sporadic forms in their genetic, epidemiologic and clinical characteristics. They require a differentiated management, especially concerning screening.

The 2-5A/RNase L pathway is one of the first cellular defences against viruses. RNase L is an unusual endoribonuclease which activity is strictly regulated by its binding to a small oligonucleotide, 2-5A. 2-5A itself is very unusual, consisting of a series of 5'- triphosphorylated oligoadenylates with 2'-5' bonds. But RNase L activity is not limited to viral RNA cleavage. RNase L plays a central role in innate immunity, apoptosis, cell growth and differentiation by regulating cellular RNA stability and expression. Default in its activity leads to increased susceptibility to virus infections and to tumor development. RNase L gene has been identified as HPC1 (Hereditary Prostate Cancer 1) gene. Study of RNase L variant R462Q in etiology of prostate cancer has led to the identification of the novel human retrovirus closely related to xenotropic murine leukemia viruses (MuLVs) and named XMRV.

HLA-G (Human Leucocyte Antigen-G) is a non-classical HLA class I molecule observed for the first time in human cytotrophoblast. Numbers of investigations have demonstrated that HLA-G was broader than originally thought. In fact, it is expressed in pathological contexts as well as in physiological contexts. This expression of HLA-G and its receptors in immunity cells confer to it a major role in immune responses. Good issues were described in organ transplantation when HLA-G was expressed. But, HLA-G transcripts and/or proteins expression in tumor tissues was associated with tumor genesis and cancer progression. A focus on the expression and the role of HLA-G in tumor context will be developed in this review. In addition, regulation of HLA-G will be treated to improve strategies of cancer therapy.