Breast cancer heterogeneity has been deciphered during the last decade thanks to the use of high-throughput tools. A major clinical concern is the determination of the metastatic risk of the tumours (prognostic factor), but also the optimal choice of the treatment for a given patient and tumour (predictive factor). A significant advance has been obtained from the description of a novel molecular classification of breast cancers. This allowed a refinement in the determination of tumour groups displaying different prognoses. Presently, numerous gene signatures have been published and some of them are on the market, at least in the United States, but prospective validation studies are still ongoing. After a major enthusiasm, numerous questions have been raised, concerning especially the stability of these signatures. An improved knowledge of these limits is also an important factor for an optimal use of these data. It can be concluded that it should be possible to improve patients' care by integrating molecular and clinicopathologic data in a common approach on the one hand, and to further develop new biomarkers predictive of therapeutic efficacy on the other hand.

Repetitive moles are rare. They are either sporadic or familial, with or without consanguinity. Some of them can be explained by a NLRP7 mutation, which causes genomic parental imprinting alteration, with a preferential paternal phenotypic expression. Currently, no effective therapeutic solution has been developed. Among the 1687 patients declared to the French Trophoblastic Disease Reference Center, 13 presented at least two hydatidiform moles, thus less than 1% of the patients. A mutation of the NLRP7 gene was shown in six of 12 tested patients (50%) among whom three presented a homozygous mutation and three a heterozygous mutation. For an affected patient, type of mole can indifferently be a complete hydatidiform mole or a partial hydatidiform mole. We describe these cases and compare them to those already published.

More than 20 years ago, the finding of a population of cells with the ability of self-renewal and differentiation inside teratocarcinomas (embryonic carcinoma cells) would allow their direct derivation from preimplantation embryos (embryonic stem cells, ESC). The phenomenal pluripotency properties of those cells and the therapeutical potential of their human counterparts triggered a massive interest from the scientific community. The research on the field of pluripotent stem cells improved a lot and many ES-like pluripotent stem cells of several embryonic and adult sources were described. Next step has been the reprogramming of terminally differentiated cells into embryonic cells, with the aim to produce patient-specific stem cells. The recent breakthrough has been the in vitro reprogramming of adult cells into ES cell-like cells named induced pluripotent stem cells (iPSC), using four transcription factors (Oct4, Sox2, Klf4, c-Myc). Even though some challenges remain, we are now one step closer to the eventuality to use these cells for clinical purposes. In this review we propose to analyse the several pluripotent stem cells existing today.

The main prognostic factors of glioblastomas (GBM) are age, neurological and cognitive status, frontal tumor location, extent of surgical resection, adjuvant therapies received, presence of IDH1 mutations, and MGMT expression. Other molecular prognostic factors have been proposed, such as mutations of TP53 and PTEN, amplification of EGFR, and deletion of 10q, but their prognostic values remain controversial. MGMT promotor gene methylation is correlated with higher chemosensitivity and consequently is a good prognostic factor only in patients treated with chemotherapy. In the future, the gene expression profile will probably be a stronger prognostic factor than histological grade, but the most relevant gene clusters, whose expression may be correlated with survival, remain to be identified. Long survivors are characterized by younger age, better neurological status, and a more aggressive therapeutic strategy. In daily clinical practice, recursive partitioning analysis (RPA) classifications can estimate the median survival of a given patient according to several basic factors. RPA class is also important so as to adapt individual therapeutic strategies, considering that the benefit of adjuvant treatments tends to decrease in the highest RPA class patients.

Human genome consists of 23 pairs of chromosomes, bearing our genetic information. Basically, there are two main approaches to analyse our genome: molecular genetics with direct sequencing, which detects genic mutations, and cytogenetics with the karyotype, which detects number and structural chromosomal anomalies. The main limitation of the karyotype is its level of resolution: it cannot detect abnormalities smaller than five megabases. The combined use of cytogenetics and molecular genetics has allowed the development of several new techniques that provide a comprehensive analysis of the genome with a very high level of resolution. Currently, the most efficient of those techniques is comparative genomic hybridization on microarray (array CGH), which already has diagnostic applications. However, those new methods are challenging to interpret and they raise ethical problems. Therefore they must be cautiously supervised.

BRAF V600E mutation in papillary thyroid carcinoma (PTC): prevalence and detection in fine needle aspiration (FNA) specimens.

Merkel cell carcinoma (MCC) is a neuroendocrine carcinoma of the skin of poor outcome. A new type of virus, isolated in 2008, was found to be strongly associated with CCM. This virus, belonging to the family of polyomavirus, was called MCPyV for Merkel Carcinoma Polyomavirus. Recent data favour a causative role of MCPyV in oncogenesis. MCC represents thus a new model for the understanding of the mechanisms of oncogenesis. The distinct molecular viral signature in every case of MCC represents an original tool for the follow-up of the disease. New therapeutic perspectives are to be drawn using this model.

Glioblastomas are the most malignant gliomas of the central nervous system. Currently, numerous studies are attempting to decipher their genetic and epigenetic modifications, to identify the cells at the origin of gliomagenesis, and to better understand the molecular bases responsible for invasion and angiogenesis processes.

The recent explosion of hereditary breast cancer genetic research has strengthened our understanding of genetic influences on health and disease. These scientific advances have significant implications for clinical oncology nurses and advanced practice nurses. In this paper, the Human Response to Illness Model (Mitchell, Gallucci, & Fought, 1991) is utilized to gain a comprehensive understanding of breast cancer related to the human response of genetic mutations. Accordingly, the research literature related to the physiological, pathophysiological, behavioural, and experiential perspectives of BRCA-related breast cancer will be highlighted. This research-based evidence will provide oncology nurses with the skills to establish a holistic plan of care for women with an actual or potential genetic risk for breast cancer.

The treatment of soft tissue sarcomas of limbs should be discussed within an experienced multimodality team. Surgical resection remains the cornerstone of therapy for localized disease and achieves a five years overall survival around 75% and a local recurrence rate as low as 10% in the best series. In complex cases, neo-adjuvant treatments may be used such as systemic chemotherapy, isolated limb perfusion, or radiotherapy to achieve an optimal conservative approach. Molecular genetics of sarcomas and quality of margins are essential to guide diagnosis and therapeutic selection. In case of marginal or incomplete resection, a new enlarged surgical resection should always be discussed before administration of any adjuvant treatments. Many retrospective studies and two randomized studies (one of adjuvant brachytherapy and one of external beam radiotherapy) have shown that adjuvant radiotherapy after complete surgery significantly reduces the risk of local recurrence in extremity soft tissue sarcomas. A randomized study has compared pre- to postoperative radiotherapy. The results in terms of local control are similar in both arms. The risk of surgical complications is higher in the preoperative arm and the risk of late sequelae is higher in the postoperative arm. A randomized study within the French sarcoma group is ongoing evaluating the omission of postoperative radiotherapy in favourable cases. Presently, the role of systematic first-line invasive treatment (including surgery and/or radiotherapy) of desmoids is debated. It is becoming evident that up to 50% of patients with desmoids benefit from a front-line non-aggressive policy, because growth arrest is a common feature of this disease. Additional study of the molecular determinants of desmoid behaviour is needed to guide treatment.

Tuberous sclerosis complex is a genetic multisystem disease characterized by hamartic development of many organs, most notably the brain, heart, kidneys, lungs, and skin. This autosomic dominant disorder results from mutations in one of two genes, TSC1 and TSC2, coding for hamartin and tuberin, respectively. The hamartin-tuberin complex inhibits the mammalian target of rapamycin pathway, which controls cell growth and proliferation. The clinical presentation is highly variable and most features of tuberous sclerosis become evident only in childhood after the child is several years of age, limiting their usefulness for early diagnosis. The aim of this article is to define the pediatric clinical manifestations of tuberous sclerosis in correlation with patient age. Sometimes, a prenatal diagnosis can be made based on fetal ultrasound and MRI, which show cardiac and brain lesions. However, newborns are most often asymptomatic. In the 1st year, seizures are the most common symptoms, with a high incidence of infantile spasms. In children between 2 and 10 years of age, neurological symptoms are the most frequent with epilepsy, mental retardation, and autism, but extraneurological manifestations can be diagnosed. In adolescents, most features of tuberous sclerosis become evident and renal and pulmonary manifestations must be sought. The knowledge of age-dependent clinical features of tuberous sclerosis can provide an earlier diagnosis and improve the management of these patients with a special role for multidisciplinary consultation.

Studies performed during these last 30 years have had a major impact on the understanding of carcinogenesis. They have opened a new field: cancer genetic predisposition. At the present time, most of the cancer predispositions linked to the alteration of one gene, associated with a high risk of cancer and with a specific phenotype have been identified. About 70 genes have been identified and have led to genetic testing. The indication of genetic testing, the management of at risk patients require the establishment of guidelines. The next challenge is the identification of cancer susceptibility genes associated with low risk or modifying the effect of treatment.

Our understanding of hereditary forms of breast cancer has made enormous advances over the past 15 years, based on epidemiological and molecular genetic studies, and the development of a vast number of informative genetic markers. These studies have involved women with both familial and sporadic forms of breast cancer. Genetic susceptibility to breast cancer can involve several modes of inheritance: Mendelian inheritance, mostly involving autosomal dominant mutations with high penetrance and a high risk of malignancy (the BRCA1, BRCA2, TP53, PTEN and STK11 genes); dominant mutations associated with a lower risk (ATM, BRIP1, PALB2, etc), and multigenic patterns involving common susceptibility variants, i.e., polymorphisms located within predisposing gene loci (FGFR2, TNRC9, MAP3K1, LSP1, etc.) or intergenic regions. Other predisposing factors remain to be discovered, as genetic factors associated with a high breast cancer risk (BRCA1, BRCA2, TP53, PTEN STK11, etc) are only found in about 20% of genetically screened breast cancer families. So far, only the first class of genes have found clinical applications, guiding the choice of medical or surgical treatment. More refined individual risk profiles will benefit from genome-wide polymorphic DNA variant studies anda better understanding of the impact of non genetic factors, such as the obstetrical and gynaecological history, and mutagen exposure.

Despite debulking surgery and taxane/platinum-based chemotherapy, ovarian cancer is the most lethal pelvic gynaecological cancer in western countries, with a 25% 5-years survival. Current histo-clinical prognostic factors are insufficient to capture the heterogeneous clinical outcome of patients. A better molecular characterization of the disease is crucial to refine the prognostic classifications and to identify new therapeutic targets. DNA microarrays, which allow the quantitative measurement of expression level of the whole genome simultaneously in a single tumor sample, have been recently used towards this objective with promising results. Here, we present and discuss the main published studies and the issues to address in the future to allow the expected transfer to clinical practice.

Pituitary adenomas were previously thought to be rare. However, a recent cross-sectional study conducted in Liège, Belgium, showed that clinically apparent pituitary adenomas were present in about 1 in 1000 inhabitants, which is 4 to 5 times the previously reported prevalence. Pituitary adenomas are generally sporadic, but some are associated with familial-isolated tumoral syndromes (mainly MEN1 and Carney complex). With the recent characterization of FIPA (Familial Isolated Pituitary Adenomas), familial pituitary adenomas are now thought to account for 5% to 8% of all pituitary tumors. New genetic mechanisms are being identified, improving our understanding of the complex manifestations and sometimes unpredictable outcome of pituitary adenomas.

Pituitary adenomas are benign tumors that can be classified according to the type of hormone they produce, immunocytochemical characteristics (which generally confirm the clinical classification) or, as proposed by WHO in 2004, specific differentiation markers of the various ligneages. The pathophysiology of pituitary adenomas is largely unknown. Although a clonal origin is very likely, no univocal molecular abnormality (except for gsp mutations, found in 40% of somatotropic adenomas) has yet been found. Studies of cell cycle proteins, growth factors and oncogenes are beginning to shed light on the complex underlying mechanisms.