A novel BRCA2 in frame deletion in a Tunisian woman with early onset sporadic breast cancer.

BACKGROUND: Breast cancer is increasing among young women in Tunisia. Germline mutations in the BRCA1/2 genes are associated with a high risk for breast cancer development. However, the true contribution of BRCA1/2 mutation in sporadic breast cancer is not well documented. Our aim is to identify the BRCA2 mutation spectrum in Tunisian young women with breast cancer. METHODS: Screening the BRCA2 gene was performed using DHPLC, DNA sequencing and PCR-RFLP. RESULTS: We identified, in a woman diagnosed with early onset breast cancer, and without family history, a novel in frame deletion 5456delGTAGCA in the exon 11 of the BRCA2 gene which causes a loss of two residues Ser1743-Ser1744. The absence of this deletion in the patients' parents suggests that it is a de novo variant. Furthermore, we screened 108 sporadic cases, 50 familial cases, and 60 controls for the identified del6bp using PCR-RFLP. None of them carried this deletion suggesting that this variant is not a benign polymorphism and probably rare in our population. With regards to the position of the Ser1743-1744 in the BRCT domain, sequence alignment revealed that the Ser1743 is conserved among several species, which may reflect its importance in the BRCA2 function. A modeling of the wild-type and mutated BRC5-BRC6 domain revealed that the deletion of the 2 Serine residues might affect the structure of this BRCA2 domain. CONCLUSIONS: A novel in frame deletion 5456del6bp in BRCA2 gene was identified in an early onset woman with breast cancer and without family history.

[Juvenile nasopharyngeal carcinoma: anatomoclinic, biologic, therapeutic and evolutive aspects]. / Les cancers du cavum juvéniles: aspects anatomocliniques, biologiques, thérapeutiques et évolutifs.

Nasopharyngeal carcinoma (NPC) represents one of the most frequent epithelial tumours of the child in intermediate risk regions. In the Maghreb, it represents the first cancer of teenagers of 15-20 years old. The Epstein Barr virus (EBV) is the most important etiologic factor. Its role in the pathogeneses of NPC has been confirmed by several studies. Young NPCs are characterized by a low rate of EBV antibodies and a high level of LMP1 cell expression than in adult's NPC. The undifferentiated carcinoma nasopharyngeal type (UCNT) represents the most frequent histological type. Immunohistochemical analyses of North Africa early onset NPC is characterized by a weak expression of bcl-2 and p53 and a strong expression of LMP1 and c-kit what makes them different from the adult's NPC. Clinically, cervical node involvement is constantly present. Juvenile NPC is characterized by a very important locoregional extension as well as a high rate of distant metastases. More than 15% of patients had metastases at diagnosis. Radiotherapy is still the standard therapy of NPC. Only some retrospectives studies have been published to determine the benefit, the type and the timing of the chemotherapy in the treatment of juvenile NPC. Metastatic relapses constitute the main cause of death at these young patients. An improvement of the prognosis can be waited with concomitant chemotherapy and intensity modulated radiotherapy. However, randomized multi institutional studies are necessary to standardize the treatment of the NPC in childhood.

[North African and Southeast Asian nasopharyngeal carcinomas: between the resemblance and the dissemblance]. / Le carcinome nasopharyngé en Afrique du Nord et dans le Sud-Est asiatique: entre similitude et différence.

Nasopharyngeal carcinoma (NPC) is an unusual head and neck cancer because of its unequal geographical distribution and its consistent association with the Epstein-Barr virus (EBV). This malignant tumor poses a serious public health problem in many countries, especially in Southeast Asia and North Africa where the recorded incidence are highest. During the past decade, a growing number of studies were undertaken to define the molecular basis of NPC. However, the analysis of several clinical and biological parameters of North African and Southeast Asian NPCs has shown notable differences, suggesting that they could result from a distinct combination of etiological factors. One intriguing characteristic of North African NPC, concerns its bimodal age distribution with a secondary peak of incidence in the range of 15-25 years, not observed in Asian NPC. In this juvenile form of NPC, immuno-histochemistry assay has shown that the two key proteins controlling the apoptotic-survival balance p53 and Bcl-2 are less frequently expressed whereas the transmembrane tyrosine-kinase receptor c-kit and the main EBV oncoprotein LMP1 were more abundant. In addition, the EBV serological alterations are less informative for the diagnosis of the juvenile compared to the adult form. In addition, most North African NPCs contain EBV strains with genetic polymorphisms distinct from those described in the Southeast Asia series (predominance of F, D, H1-H2, XhoI+ and f, C, H, XhoI- respectively). In contrast, studies relating on tumor chromosomal alterations or aberrant promoter methylation result in data very similar to those obtained from the Southeast Asia series, supporting the concept of a common molecular basis for all NPC regardless of patient geographic origin.

[Pediatric nasopharyngeal carcinoma: Anatomoclinic aspects, therapeutic results and evolutive particularities]. / Le cancer du cavum de l'enfant et l'adulte jeune : aspects anatomocliniques, thérapeutiques et particularités évolutives.

PURPOSE: We retrospectively analyzed anatomoclinic, therapeutic and evolutive particularities of 74 young patients (< or =20 years) with nasopharyngeal carcinoma treated between 1993 and 2005. PATIENTS AND METHODS: Initial work-up included a fiberoptic nasofibroscopy with biopsy, tomodensitometry and/or MRI of nasopharynx and neck, chest X-ray, abdominal ultrasonography and bone scan. Patients were treated with either primary chemotherapy (epirubicin and cisplatin) followed by radiotherapy or concomitant radiochemotherapy (five fluorouracil and cisplatin). Radiotherapy was delivered to a total dose of 70 to 75 Gy to nasopharynx and involved cervical lymph nodes and 50 Gy to the remainder cervical areas. RESULTS: The median age was 16 years. Sixty-three percent of patients had undifferentiated tumors. Sixty-six percent had locally advanced tumor. With a median follow-up of 107 months, one patient presented a local relapse, 24 patients developed distant metastases with a median delay of 7 months. The 5 years overall survival and disease-free survival were 66 and 65 %. Late complications were dominated by dry mouth and endocrine disorders. COMMENTS: Pediatric nasopharyngeal carcinoma is characterized by an early metastatic diffusion. Local control is excellent but with severe late toxicities. New techniques of radiotherapy and new molecules of chemotherapy could improve these results.

In situ immunocytochemical detection of potyviral proteins in plant cells.

A method for in situ protein immunodetection using a peroxidase labeling system is described for detecting functional and structural proteins encoded by potato virus Y (Tunisian isolate) in plant tissues. Such Potyviruses are characterized by the accumulation of inclusion bodies containing viral encoded proteins other than coat protein. These proteins are functional at early stages of infection, making them easy to detect. Data are compared to those obtained by immunofluorescence techniques. Our technique can be used as a preliminary method for rapid detection of virus infection using antibodies directed against functional proteins.

Inhibition of potato virus Y NIa activity: preparation of monoclonal antibody directed against PVY NI protein that inhibits cleavage of PVY polyprotein.

A partially purified nuclear inclusion (NI) fraction was obtained from tobacco plants infected by potato virus Y (PVY). Four monoclonal antibodies (MAbs) were produced and characterized using this semipurified fraction as antigen. Data showed that only one was directed against NIa whereas two were directed against cytoplasmic inclusion (CI) protein and the last one against coat protein (CP). These results were due to the fact that the semipurified NI fraction was usually contaminated with CI and CP proteins. When used on in situ immunofluorescence method the anti-NIa MAb showed accumulation of the NIa protein in both nucleus and cytoplasm. In vivo, this MAb was able to detect different forms of the NIa protein including precursors and cleavage products. It was also able to inhibit the cleavage of the polyprotein detected in the semipurified NI.

Translational control of human p53 expression in yeast mediated by 5'-UTR-ORF structural interaction.

We have expressed human p53 cDNA in the yeast Saccharomyces cerevisiae and shown that the level of production and the length of the p53 protein depends on the presence of untranslated mRNA regions (UTRs). The expression of the ORF alone leads to a p53 protein of correct size (53 kDa) that accumulates to high levels, concomitantly with the presence of a small amount of a p40 protein (40 kDa). However, when either the entire 5'-UTR and a part of the 3'- or 5'-UTR alone is used, this leads to the production of small amounts of the 40 kDa truncated form only. The p40 protein corresponds to a truncated form of p53 at the C-terminal extremity since it reacts only with a monoclonal antibody recognising the N-terminal epitope. This effect on the amount and length of p53 protein had no correlation at the mRNA level, suggesting that translational control probably occurs through the 5'-UTR. We propose a model of structural interaction between this UTR and a part of the ORF mRNA for the regulation of p53 expression in this heterologous context.

Genotyping of Tunisian hepatitis B virus isolates based on the sequencing of preS2 and S regions.

The S nucleotide sequences of five hepatitis B virus strains isolated from plasma samples of Tunisian patients with chronic hepatitis B were determined; the preS2 region of three of them were sequenced. According to the comparative analysis of S peptide sequences with the reported sequences in the database bank, the five hepatitis B strains were shown to be related to the D genotypic group, subtype ayw. The nature of residues at positions 125 and 127 allowed us to distinguish between each subtype of the D group and to class all five Tunisian sequences in the 'ayw2' subtype. Moreover, two of them (1366 and 523) contained a substitution of the invariant Cys69 by Arg and Cys221 by Phe, respectively. Potential structural modifications due to the Cys-Arg change are discussed.

[Angina and myocardial ischemia related to a fistula between the anterior interventricular artery and the pulmonary artery in a 56-year-old man]. / Angor et ischémie myocardique liés à une fistule entre l'interventriculaire antérieure et l'artère pulmonaire chez un homme de 56 ans.

The authors report a case of fistula between the left anterior descending artery (LAD) and the pulmonary artery (PA), in which the only clinical expression was angina associated with electrical signs of myocardial ischaemia on exertion. In the absence of any other signs of left-right shunt related to the fistula, the initial diagnosis was that of atherosclerotic coronary artery disease, especially as this 56-year-old man presented three risk factors. Coronary angiography revealed this anomaly and corrected the diagnosis. Surgical closure of the fistula under cardiopulmonary bypass and via a pulmonary artery approach led to resolution of the angina and exertional ischaemia. Similar cases of LAD-PA fistula responsible for angina as the only clinical manifestation and discovered on coronary angiography have been rarely reported in the literature.

[A case of esophageal duplication discovered in a newborn]. / A propos d'un cas de duplication oesophagienne de révélation néonatale.

A case of esophageal duplication discovered in the neonatal period is reported and discussed. This infrequent malformation (9% of all childhood mediastinal tumors) is an entoblastic duplication of the digestive tract and is often accompanied with spinal malformations. The duplication may be either cystic or tubular; the latter form usually opens into the normal esophagus. The most common clinical manifestations are respiratory symptoms caused by compression. The diagnosis, suggested by the findings on the plain chest film and osephageal opacification, is confirmed by the ultrasound examination and, above all, the CT scan. The treatment of this malformation is surgical. Reconstruction may be difficult but overall results and prognosis are excellent.

[Long-term outcome of surgically treated peptic ulcer. Review of a series of 419 patients operated for peptic ulcer]. / Le devenir lointain de l'ulcère gastro-duodénal opéré. Réflexions sur une série de 419 ulcéreux opérés.

The authors report an analysis of 419 cases of operated peptic ulcer. 68.78% of patients had a mean follow-up of 4 years. After clinical and endoscopic examination, the results of the survey were assessed on the basis of various parameters, which demonstrated that the results of surgery were related to socio-occupational problems, smoking, the site of the ulcer, the stage, the history of the ulcer prior to the operation, the conditions of the operation and obviously the surgical technique used.

[Hydatic cyst of the psoas muscle. Apropos of 3 cases]. / Le kyste hydatique du muscle psoas. A propos de trois cas.

In the three patients, the localization and the hydatic origin have been determined by preoperative ultrasonography in two instances, the diagnosis was confirmed by CT scan. Ultrasonography and computed tomography allowed a direct and simple surgical approach of the cyst.

[Hydatid cyst of the brain. Apropos of a series of 14 cases]. / Le kyste hydatique du cerveau. A propos d'une série de quatorze cas.

The authors report a series of 14 cases of cerebral hydatid cysts. This is a rare site (1.5% of all sites) which usually presents in the form of intracranial hypertension, sometimes associated with localizing signs, the diagnosis is no longer a problem since the development of computed tomography. Treatment is exclusively surgical and the prognosis depends on the degree of preoperative neurological impairment. Twenty-eight per cent of cases had postoperative neurological sequelae which stresses the importance of early diagnosis and treatment.

Mechanism of synthesis of turnip yellow mosaic virus coat protein subgenomic RNA in vivo.

Turnip yellow mosaic virus (TYMV) possesses a monopartite single-stranded (+) sense RNA genome in which the coat protein (cp) gene is 3' proximal and is expressed in vivo via a subgenomic RNA. Evidence is presented here that this subgenomic RNA is synthesized in vivo by internal initiation of replication on (-) RNA strands of genomic length. The double-stranded RNAs (dsRNAs) from TYMV-infected plants have been isolated, purified, and characterized. Under native conditions, no dsRNAs (replicative intermediates and/or replicative forms) of subgenomic length corresponding to subgenomic cp RNA can be detected by ethidium bromide staining of RNA-sizing gels or by Northern blot hybridization using RNA probes. The presence of nascent subgenomic cp (+) RNA strands on the dsRNA of genomic length has been demonstrated using two different approaches: (1) Northern blot hybridization using (-) RNA probes under denaturing conditions and (2) characterization of the 5' ends of nascent (+) RNA strands upon labeling by vaccinia virus nucleoside-2'-methyltransferase.

[Anterior trans-scapho-perilunate dislocation of the wrist]. / Luxation transcaphopérilunarienne antérieure du carpe.

Anterior trans-scapho-perilunate dislocation of the wrist is an extremely rare lesion. Based on a case report and a review of the literature, the authors describe the mechanism, treatment and course of this lesion.

Plant viruses and new perspectives in cross-protection.

Cross-protection in plants is the phenomenon whereby a plant preinoculated with a mild virus strain becomes resistant to subsequent inoculation by a related severe strain. It has been used on a large scale in cases where no resistant plants are available. Although several hypotheses have been proposed to explain the molecular mechanism underlying cross-protection, no single hypothesis can account for all the data obtained. Recently, a phenomenon akin to cross-protection has been achieved in transformed plants harboring the cDNA of a part of a viral RNA genome. These results obtained by genetic engineering raise new hopes for obtaining plants resistant to virus infection.