Early-onset breast cancer characterize genetic predisposition to cancer in women. BRCA-1 gene was identified as one of the predisposition genes of breast/ovarian cancer. About 90% of the reported mutations in the hereditary breast and ovarian cancer gene, BRCA-1, result in truncated proteins. The aim of our study is to detect rapidly BRCA-1 mutations by the protein truncation test (PTT) in Tunisian women with early breast cancer. Population and methods. We underwent molecular analysis in families with more than: (a) a women under 40 years-old with breast cancer, uni or bilateral; (b) two 1st degree relatives women under 50 years-old with beast cancer. Sixteen women from 12 families were studied by PTT to screen mutations in exon 11 which encodes 61% of BRCA-1.

The t(1;22)(p13;q13) translocation is specifically associated with infant acute megakaryoblastic leukemia (M7). We have recently characterized the two genes involved in this translocation: OTT (One Two Two) and MAL (Megakaryoblastic Acute Leukemia) respectively located on chromosome 1 and 22. The t(1;22) translocation results in the fusion of these genes in all the cases studied to date. We summarize here present knowledge regarding this translocation.

Prostate cancer is the second cause of cancer death in men. Often, initialy hormono-independent, escape from anti-androgen therapy is a key event of tumoral progression showing an hormone-independent phenotype. To study morphological, genetic and molecular bases associated with the hormono-dependence escape, a new model of human adenocarcinoma prostate xenograft, PAC120, was established with its hormono-dependent and independent variants. Its growth was strongly inhibited by surgical castration or by administration of the new gonadotrophin-releasing hormone antagonist, FE 200486 (Ferring, San Diego, CA). Evolution to hormono-independence was frequently associated with a mucoid differentiation or a neuroendocrine-like pattern, with the apparition of new chromosomic alterations and variations of human gene expressions. PAC120 xenograft is a new model of hormone-dependent prostate cancer, opening the opportunity to study the hormone dependence escape mechanism and to evaluate the efficacity of new therapeutics.

EARLY DIAGNOSIS FOR EFFICIENT MANAGEMENT: The melanoma is a cutaneous tumour of poor prognosis and its incidence is increasing. Some risk factors are now well established ( field, phototype, family history) and its early discovery is clinically possible since the lesions are visible to the eye. When diagnosed early, the prognosis is clearly improved. CLINICAL FORMS OF VARYING PROGNOSIS: Depending on the clinical, histopathological and progressive differences, it is possible to distinguish a Superficial Spreading Melanoma (60 to 70%), nodular melanoma (10 to 15%), Dubreuilh's melanoma (5 to 10%) and acrolentigenous melanoma (5%). Apart from these 4 major clinical forms, there is also the sub-ungual melanoma and the mucosal melanoma. Particular situations may also exist: the discovery of metastasis without identification of cutaneous tumour, a melanoma in a pregnant woman or a child, a familial melanoma or multiple melanomas. THE ELEMENTS OF DIAGNOSIS: The semiological analysis of an often-pigmented lesion of the skin, relying on the ABCDE rule and the notion of rapid progression, is the first stage in the diagnostic approach. It is completed, following complete exeresis, by anatomopathological exploration (Breslow's index, existence of ulceration, signs of regression, Clark's classification, histological type and mitotic activity). Two further elements should also be taken into account: the results of a dermatoscopy and the analysis of the sentinel nodes.

A WORRYING INCIDENCE: In frequency, the melanoma, is placed just after breast, colic and pulmonary cancer with around 6 000 new cases per year in France. Moreover, it is the tumour that is increasing the most and its frequency has doubled over the past 10 years. It is presently estimated as 7 to 9/100 000 in France. THE IMPACT OF PREVENTIVE MEASURES: Primary and secondary prevention is therefore crucial, as is the identification of patients at risk. However, till now, the impact of educational and preventive campaigns with regard to sun exposure, which plays a major role in the development of a melanoma, are still insufficient

Gastrointestinal stromal tumors (GIST) are rare tumors occuring at all levels of the gastrointestinal tract, whose estimated incidence may be close to 2 new cases per 100 000 persons per year. GIST derive from the interstital cells of Cajal (ICC) responsible for the motility of the GI tract, or from a common precursor of ICC and of the smooth muscle cells of the digestive tract. GIST cells express the c-kit protoconcogene under an activated form, either mutated or constitutively activated, as well as the CD34 Ag. Mutations of the KIT gene is an early event in the process of transformation in these tumors. Until recently, GIST were not recognized as a distinct entity among soft tissue sarcoma. It is now clear that conventional chemotherapy is generally inactive in this tumor, surgery being the only efficient therapeutic modality even in patients with advanced disease. Rapidly accruing phase I, II and III trials in the USA and Europe (EORTC) have demonstrated since 2000 that imatinib mesylate (STI571) is an active agent in GIST with an initial response rate of 70 % and 10 % only of primary refractory tumors, yelding an improved overall survival as compared to historical series. Resistance are now being observed however. GIST has become the first model of a solid tumor treated efficiently by a treatment targetting the initial genetic alteration of the disease. Numerous question regarding the integration of this treatment with surgery and the long term outcome of these patients still remain to be answered however.

Bladder cancer is an urologic common tumor after prostatic carcinoma. Treatment of bladder cancer requires an interdisdisciplinary approach, including urologist, medical oncologist and radiation oncologist. Treatment of superficial tumors is based on endovesical instillations and sometimes on radical cystectomy for pejorative recurrences. For invasive tumor, radical cystectomy is needed. At present, ileal reconstructions could be largely proposed, in men as in women, for better quality of life. For selected patients, chemoradiotherapy is a valid alternative treatment to radical cystectomy, with similar survival rates and conservation rates of functional bladder about 50-60 %. In spite of the efficacy of local treatment, almost one half of patients develop metastasis. Recently, new drugs like paclitaxel, gemcitabine or Herceptin are available to improve the management of metastatic disease.

Chemotherapy has emerged to be a central component of curative strategies for patient with primary squamous cell carcinoma of the head and neck. The identification of agent active in head and neck cancer first occurred in patients with local regional recurrent and/or metastatic disease treated with palliative intent. The present paper reports the prognostic factors which based the understanding of these patients outcome. A review of the relevant results obtained by the standard chemotherapy in this recurrent population is performed. The current and future area of research were highlighted.

The progress in the knowledge of molecular genetics and the availability of high-throughput technologies offer the opportunity to identify new diagnostic and prognostic markers and new therapeutic targets in human cancer. The recently developed "tissue microarraysî (TMA) technology allows parallel molecular profiling of clinical samples. Using this technique and immunohistochemistry (IHC), fluorescence in situ hybridisation (FISH), or RNA in situ hybridisation (ISH), the pathologist is now able to perform unprecedented large-scale analyses. The advantages are significant: large number of cases assessed simultaneously for numerous markers, processing in identical conditions, reduced amount of archival tissues, excellent correlation with standard methods, reduction in cost and time. This article provides a short review of this technology, and points out several aspects of the TMA construction and its applications for clinical research.

Xeroderma pigmentosum is a relatively frequent genodermatosis in North Africa. It is characterized by abnormal sensitivity to ultraviolet light, responsible for the early occurrence of multiple cutaneous neoplasms. We present the results of the clinical and biological investigations in a family in which all its members exhibited xeroderma pigmentosum.

Inflammatory myofibroblastic tumors (IMT) are mesenchymal solid tumors that occur preferentially in children and young adults. They present as myofibroblastic cell proliferations accompanied by plasmocytes and lymphocytes. Recent cytogenetic and molecular observations showed non-random abnormalities of chromosomal band 2p23 resulting in a rearrangement of the ALK gene. This finding of a specific gene alteration suggests a neoplastic rather than a reactive inflammatory process for IMT tumorigenesis. ALK is a tyrosine kinase oncogene initially found to be rearranged in anaplastic large-cell lymphomas (ALCL). Of note, the breakpoints within ALK, and also within some of the ALK fusion gene partners, such as TPM3 or CLTC, are similar in IMT and ALCL. The consistent involvement of ALK, together with the diversity of partner genes, underlines the central role of ALK constitutive activation in IMT development, as well as the importance of homodimerization mechanisms of the chimeric fusion proteins in this activation. Immunohistochemical analyses performed on paraffin embedded tissue sections have shown positive ALK expression with cytoplasmic localization in half of the IMT cases containing the molecular ALK rearrangement. In conclusion, these novel molecular data have defined a group of IMT of neoplastic origin characterized by the presence of ALK alterations. The description of ALK gene rearrangements in IMT and ALCL is the second example, after the observation of ETV6-NTRK3 in congenital fibrosarcoma and in a case of chronic myeloid leukemia, of identical gene fusions occurring in two different cell lines: hematopoietic and mesenchymal. The search for rearrangement of ALK by fluorescence in situ hybridization (FISH) is a useful complementary tool for IMT diagnosis.

Numerous studies deal with "p53 status" in patients' tumors (mutated/wild gene status, protein level and functionality) to predict chemotherapy efficacy. Analyses of various cancers, especially breast cancers, lead to controversy that is apparent due to heterogeneity of their design. Recent data from literature lead now to consider i) the nature of chemotherapeutic agents and the regimen, ii) the cancer tissue type, and iii) the histological response of the primary. Molecular actors of senescence, cytostasis and apoptosis, which are responsible of cytotoxic response of cancer cells, are currently under elucidation.

We prospectively evaluated 30 patients with CNS cavernous angioma with a high field (1.5T) magnetic resonance imager. In all patients the MRI protocol included: gradient echo T1*-weighted imaging, spin echo T2*-weighted imaging and gradient echo T2*-weighted imaging. We evaluated each case for the number of lesions detected on each sequence. Gradient echo T2*-weighted imaging with a long TE (TE: 35ms) was the most sensitive sequence for the detection of cavernous angiomas allowing detection of small lesions that were not identified on the other sequences.

The BRCA1 et BRCA2 genes are involved in 2/3 of genetic predisposition with major risk of breast cancer. One or more genes remain to be identified. The CHEK2 gene is a good candidate. The CHEK2 gene mutation 1100delC is associated with a moderate increase of breast cancer risk (RR = 2). CHEK2 is probably one of the genetic factors associated with moderate risk, but however when associated with other variants, it could explain some familial breast cancer and sporadic cancer cases. It seems to be too early to include CHEK2 in genetic counselling at the present time.

Progress in techniques and computer processing over the last few years have led to the development of new methods of molecular biology. These new methods allow rapid data processing, often allowing data to be shared via networks. An example of this new technology is the transcriptome analysis via a microarray chip. This chip allows analysis of a very large number of RNA messenger transcripts that can be used for diagnostic or prognostic purposes. The first applications in lung cancer have been aimed to distinguish pulmonary adenocarcinoma from other adenocarcinomas. Another approach is to use these chips as a diagnostic tool to identify genes with expressions specific for non-small-cell lung cancer. The early results have been promising and encouraging for future developments, particularly in the domain of applied therapeutics.

Pancreatic endocrine tumors are uncommon. Although the great majority of these tumors are well differentiated, their malignant potential varies sometimes greatly. Thus, a variety of clinicopathologic features have been developed in the past to assist in distinguishing pancreatic endocrine tumors with benign, indeterminate and aggressive behavior. Recently, a revised classification of pancreatic endocrine tumors has been proposed including, in addition to previous parameters, the number of mitoses and a Ki-67 index. In this review, the potential diagnostic utility of these different criteria is discussed.

Pancreatic carcinogenesis is still not well characterized and no specific carcinogen has been isolated in humans. Pancreatic adenocarcinoma acquires genetic abnormalities with successive modification of genes involved in the regulation of cell proliferation and differentiation. The kinetic of genetic alterations in pancreatic cancer is not totally elucidated but experimental pancreatic cancer induced by BOP in Syrian golden hamster attempts to approach this problematic. The activating mutation of the K-ras oncogene on codon 12 seems to occur early in pancreatic carcinogenesis regarding the detection of this mutation in preneoplastic dysplastic lesions and tumors such as intraductal mucinous papillary tumors. Tumor suppressor genes are also inactivated leading commonly to the loss of an inhibitory function on cell proliferation. This inactivation occurs with gene mutation, deletion or methylation on one chromosome arm associated with a loss of heterozygosity: it concerns p53, p16/MTS-1, DPC-4/SMAD4. We recently characterized the somatostatin receptor SST2 gene as a potential suppressor gene for pancreatic carcinoma. The kinetic of these gene alterations is unknown in human. At a late stage of tumor development, an increase of telomerase activity, an over expression of growth factors and/or their receptors (EGF, NGF, gastrin, bombesin), of proangiogenic factors (VEGF, FGF, PDGF), of invasiveness factors (metalloproteinases, E-cadherin, urokinase and tissue plasminogen activators) occur. All these molecular events contribute to the progression and to the metastatic potential of this carcinoma. Recently, the identification of human genome and the large scale analysis of transcriptoma will certainly authorize a better knowledge of pancreatic carcinogenesis as well as the identification of new genetic alterations and new clinical markers.