[Show abstract][Hide abstract] ABSTRACT: The cell-cycle checkpoint kinase 2 (CHEK2) is an important signal transducer of cellular responses to DNA damage, whose defects has been associated with increased risk for breast cancer. The CHEK2 1100delC mutation has been reported to confer a twofold increased risk of breast cancer among carriers. The frequency of the mutation varies among populations. The highest frequency has been described in Northern and Eastern European countries. However, the 1100delC mutation has been investigated in different case-control studies and none in Moroccan population. The aim of this study was to evaluate the prevalence of this variant and determine its contribution to the development of breast cancer in sporadic cases and also in members of breast cancer families who tested negative or positive for a deleterious mutation in BRCA1/BRCA2.
In this case-control study we performed the CHEK2 1100delC mutation analysis by ASO-PCR in 134 breast cancer patients and 114 unaffected control individuals. Most of these families had several cases of breast cancer or ovarian cancer (or both).
No CHEK2 1100delC mutations were detected in any of 134 individuals, including 59 women diagnosed with breast cancer at an early age (<40 years), 10 women with bilateral breast cancer, and 6 women with ovarian cancer.
Our preliminary genetic analysis are consistent with the reported very low frequency of CHEK2 1100delC mutation in North American populations (compared with Northern Europe), rendering CHEK2 1100delC such as an unlikely to be major breast cancer susceptibility genes.
[Show abstract][Hide abstract] ABSTRACT: Identification of specific mutations in cancer patients may lead to the discovery of genes, which can affect susceptibility and/or prognosis. It has previously been reported that mutations in BRCA1 and BRCA2 genes are linked to breast cancer. Here, we evaluated the use of the High Resolution Melting (HRM) approach to screen for mutations in exon 11 of BRCA1 gene in Moroccan patients.
HRM analysis was used to screen exon 11 from 71 breast cancer patients in order to detect different variants. Conventional Sanger sequencing was used to confirm the presence of possible mutations. Distribution of different SNPs was determined by SNaPshot analysis software.
In order to assess the efficacy of the HRM approach to screen for mutations, especially in diagnosis, we first used two samples with previously known mutations, "2924delA and 3398delC". Indeed, these previously known sequence variants were detected by the HRM approach and yielded melting curves with atypical shape relative to wild-type control sequences. We then analyzed, 69 samples from breast cancer patients using the HRM method, and were able to detect two samples with atypical curves. Sequencing of the two samples, using the conventional Sanger approach, confirmed the presence of the same SNP (c.2612C > T) in both samples.
Our results strongly suggest that the HRM approach represents a reliable and highly sensitive method for mutation scanning, especially in diagnosis.
BMC Cancer 12/2015; 15(1):1040. DOI:10.1186/s12885-015-1040-4 · 3.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To describe the therapeutic results, with the aim to contribute to improving the care of patients with medulloblastoma.
Patients and methods:
A retrospective study of 69 cases of medulloblastoma collected in the university hospital Ibn Rochd of Casablanca between 2000 and 2012.
Fifty-three children with an average age of 9 years and 16 adults with an average age of 32.4 years were included in the study. Thirty-seven children and eight adults suffered from a high-risk tumour. The radiotherapy was received by all patients with a mean dose of 36Gy to the whole brain and 54Gy in the posterior fossa. All patients in the paediatric group and 10 patients in the adult group received concomitant chemotherapy, 44 children and four adults received adjuvant chemotherapy. Tumour recurrence was observed in 17 children after a mean follow-up period of 38 months. These recurrences were observed in five adults after a mean follow-up period of 42 months. The posterior fossa was the main site of relapses. Overall survival was 77.7% for the children and 61% for the adults. Overall survival was better (70% versus 25%) when the interval between radiotherapy and surgery was less than 40 days in the paediatric group. The recurrence rate was significantly higher for the high-risk group: 41% versus 13% for the standard risk. In the adult group, overall survival differences according to the risk group were significant (100% for the standard risk versus 37.5% for the high risk).
The overall survival and recurrences rate obtained are encouraging. The risk group and time between surgery and radiotherapy were prognostic factors with significant impact on survival depending on the age group. We recommend reducing these times to improve therapeutic results.
[Show abstract][Hide abstract] ABSTRACT: Imatinib, a tyrosine kinase inhibitor, is a major therapeutic option for the management of unresectable aggressive fibromatosis. Unfortunately, for most patients of low or very low average income countries, surgery often is the first treatment option. This is related to unavailability of chemotherapy or targeted therapy, and to a lack of financial resources or surgeons' lack of knowledge of other therapeutic options.
In 2010, a 26-year-old Moroccan man was referred to our oncology and radiotherapy center by his surgeon for the management of a recurrent tumor of his right subscapularis muscle. Before his assessment in our center, two resections were performed by his surgeon after performing an incision biopsy and magnetic resonance imaging. Postoperative magnetic resonance imaging was performed and showed a right axillary nodule size 2.1cm regarding a collection with a residual tumor. We decided to administer imatinib 400mg daily by mouth. Clinical and magnetic resonance imaging evaluation were performed regularly and reported a stable tumor. We reported no adverse side effects to imatinib regarding Common Terminology Criteria for Adverse Events grading.
Recurrences are high during aggressive fibromatosis management. Systemic treatment with imatinib for unresectable or recurrent tumors with positive c-KIT could be the best therapeutic option. In our case report, the patient was stabilized with imatinib for 30 months and he had a very good quality of life.
Journal of Medical Case Reports 12/2014; 8(1):416. DOI:10.1186/1752-1947-8-416
[Show abstract][Hide abstract] ABSTRACT: TP53 is a tumor suppressor gene involved in cell cycle progression control, DNA damage repair, genomic stability, and apoptosis. Some polymorphisms in this gene have been associated with the development of a number of cancers including breast carcinoma. PIN3 Ins16bp polymorphism has been widely studied in different populations for an association with breast cancer risk. In most case-control studies, a duplicated allele has been more frequent in cases rather than controls but there are also inconsistent results. The present study aimed to assess the association of PIN3 Ins16bp polymorphism of p53 with breast cancer risk in Moroccan population. This case-control study was performed on 105 female patients with confirmed breast cancer and 114 healthy controls. The genotype frequency was 69.5 % (A1A1), 26.7 % (A1A2), and 3.8 % (A2A2) in patients and 68.4 % (A1A1), 24.6 % (A1A2), and 7 % (A2A2) in controls. No statistically significant association was observed between PIN3 Ins16bp polymorphism and breast cancer risk with odds ratio of 1.07 (confidence interval (CI) = 0.58-1.97, p = 0.83) for the heterozygous A1A2 and 0.53 (CI = 0.15-1.85, p = 0.32) for mutated homozygous A2A2.According to our preliminary genetic analysis, PIN3 Ins16pb polymorphism could not be assessed as a marker of risk factor for predisposition to breast cancer in Moroccan population. However, a high frequency of A2 allele (19.3 %) in our population suggested that PIN3 Ins16pb polymorphism may be a valuable marker for study in other cancers with larger groups.
[Show abstract][Hide abstract] ABSTRACT: We report a case of adrenal metastasis from colorectal cancer in a 54-year-old woman. Nine months after resection for advanced rectal carcinoma, a computed tomography scan revealed bilateral adrenal metastasis. The level of serum carcinoembryonic antigen was normal. A bilateral adrenalectomy was performed after chemotherapy. Histopathological examination showed adenocarcinoma, compatible with metastasis from the rectal cancer. Adrenal metastasis should be considered in the patients' follow-up for colorectal cancer.
[Show abstract][Hide abstract] ABSTRACT: Germline mutations in the BRCA1 gene are known predictive markers for the development of hereditary breast cancer. Nevertheless, no comprehensive study has been performed targeting the presence and relevance of BRCA1 mutations in Moroccan breast cancer patients. We here present an analysis of BRCA1 gene regions (exon 2 and exon 11a/b) of 50 female Moroccan breast cancer patients with early disease onset (≤40 years) or familial disease backgrounds. Results showed that no mutation was present in either exon 2 or exon 11a of the BRCA1 gene in any of the 50 patients analysed. However, in exon 11b, a mutation generated by a nucleotide exchange was detected in 8% of patients, most of whom were young women (≤40). This mutation leads to substitution of the amino acid glutamine by an arginine at position 356 of the polypeptide sequence (Q356R). Although this mutation was previously characterised at a lower frequency in western populations, our study is the first to describe it in a young Moroccan population. Furthermore, another mutation was detected with a high frequency (4%) on exon 11b of the BRCA1 gene in exclusively young patients (≤40). This mutation was silent, encoding the same threonine residue at position 327 (T327T) as the wild type. The present study is the first to describe this mutation as well, particularly in a young Moroccan population. Analysis of a larger population is required in order to highlight the relevance of the Q356R and T327T mutations in young Moroccan breast cancer patients.
[Show abstract][Hide abstract] ABSTRACT: Granular cell tumour, or Abrikossoff's tumour, is a rare, ubiquitous tumour, with mostly benign evolution. The malignant forms represent 1–3% of the cases. The vulvar localization is exceptional. We report the case of a 28-year-old patient who presented a vulvar Abrikossoff's tumour. Initially considered benign, the tumour was treated by exclusive local surgery. Five months later, the tumour showed a malignant transformation. The tumour size was 14 cm in its major axis with the presence of not systematized scattered mitoses, PS 100 was positive at 100% and Ki 67 to 20%. Because of malignant and economic excision of the neoplasm, the patient received adjuvant radiotherapy. After 20 months, the patient had a local recurrence and lung metastasis, supporting the diagnosis of malignancy. She received two chemotherapy regimens of 5-fluoro-uracil/cisplatin and pacliatxel/carboplatin without any response. Following the failure of chemotherapy, the patient received symptomatic medical treatment. This observation leads to advocate an aggressive surgical treatment and strict supervision of all granular cell tumours.
[Show abstract][Hide abstract] ABSTRACT: Granular cell tumour, or Abrikossoff's tumour, is a rare, ubiquitous tumour, with mostly benign evolution. The malignant forms represent 1-3% of the cases. The vulvar localization is exceptional. We report the case of a 28-year-old patient who presented a vulvar Abrikossoff's tumour. Initially considered benign, the tumour was treated by exclusive local surgery. Five months later, the tumour showed a malignant transformation. The tumour size was 14cm in its major axis with the presence of not systematized scattered mitoses, PS 100 was positive at 100% and Ki 67 to 20%. Because of malignant and economic excision of the neoplasm, the patient received adjuvant radiotherapy. After 20 months, the patient had a local recurrence and lung metastasis, supporting the diagnosis of malignancy. She received two chemotherapy regimens of 5-fluoro-uracil/cisplatin and pacliatxel/carboplatin without any response. Following the failure of chemotherapy, the patient received symptomatic medical treatment. This observation leads to advocate an aggressive surgical treatment and strict supervision of all granular cell tumours.