[Identification of a Family with SUFU Germline Deletion Based on a Case of Desmoplastic Medulloblastoma in an Infant]. / Identifikace rodiny s nosicstvím germinální delece genu SUFU na podklade dia-gnózy desmoplastického meduloblastomu u batolete.

BACKGROUND: Medulloblastoma, an embryonal neuroectodermal tumor of the cerebellum, is the most common malignant brain tumor in children. There are approximately 15 cases diagnosed in the Czech Republic each year. The recent World Health Organization classification recognizes several histopathological subtypes of medulloblastoma: classical, desmoplastic/ nodular with its extensive-nodularity variant, and anaplastic/ large-cell variant. Further molecular analysis identified four basic subgroups of medulloblastoma: WNT, SHH, Group 3, and Group 4. The subgroup of SHH meduloblastoma is associated with somatic mutations of SHH, PTCH1, SUFU, SMO and TP53, while the most common mutations found in infants up to three years of age were PTCH1 and SUFU. The majority of medulloblastomas are sporadic diseases, whereas only about 5- 10% of all cases occur in connection with hereditary genetic syndromes. CASE: We present a case of a 21-months old girl diagnosed with a localized posterior fossa tumor. The histopathological examination revealed a desmoplastic/ nodular medulloblastoma. The treatment comprised a radical exstirpation of the tumor followed by adjuvant chemotherapy. With the use of array-CGH, a partial biallelic deletion of the SUFU gene (locus 10q24.32) was detected in the tumor DNA, whereas a monoallelic deletion was found in the peripheral lymphocyte DNA of the patient. These findings were confirmed by an independent qPCR method. Monoallelic germline deletion of SUFU was also identified in the patients mother, who was a healthy carrier. Pedigree of the family suggested a transition of the germline deletion of SUFU, since another brain tumors (including one case diagnosed before the age of three years) were identified in previous generations. CONCLUSION: Germline mutations in SUFU gene are believed to predispose to infant desmoplastic/ nodular medulloblastomas, basal cell carcinomas and meningiomas. The susceptibility gene shows autosomal dominant inheritance with an incomplete penetrance. There is no evidence-based surveillance strategy suggested for the carriers of germline SUFU mutations/ deletions so far. Our recommendation is based both on a family history of our patient and similar cases described in the literature. Since the germinal mutations in SUFU are responsible for up to 50% of all desmoplastic medulloblastomas in children under three years of age, genetic testing of SUFU should be encouraged in this population of patients.

[Profile of Activation of Tyrosine Kinases and MAP Kinases in Therapy of Maffucci Syndrome]. / Profil aktivace receptorových tyrozinkináz a mitogenem aktivovaných proteinkináz v terapii Maffucciho syndromu.

BACKGROUND: Maffucci syndrome is a rare congenital nonhereditary disease characterized by multiple hemangiomas and enchondromas, which may progress into malignancy. The causal therapy does not exist, and therapy is aimed at complications. The determination of appropriate therapy is complicated, and a multidisciplinary approach is often essential. CASE: Authors are presenting the case of a 20-year -old patient with Maffucci syndrome. During her life, multiple enchondromas and progressing hemangiomas have been revealed and they have caused many complications, such as limited movement, growth failure, pain, fluidothorax and ascites. A profile of phosphorylation of selected tyrosine kinases and MAP kinases from progressing hemangioma was performed and with consideration of the result, it led to change of treatment strategy with encouraging clinical response lasting for six months.

Successful use of metronomic vinblastine and fluorothymidine pet imaging for the management of intramedullary spinal cord anaplastic oligoastrocytoma in a child.

BACKGROUND: Children with high-grade glioma still have a poor prognosis despite the use of multimodal therapy including surgery, radiotherapy, and chemotherapy. New therapeutic strategies and methods evaluating such therapies are needed. OBSERVATION: Here we describe a child with anaplastic oligodendroglioma of the spinal cord who was unable to tolerate standard chemoradiotherapy and who had still-vital residual tumour during therapy. A good response was obtained with low-dose metronomic treatment containing vinblastine. The treatment was guided according to gradual response assessed using various positron-emission tomography tracers. CONCLUSIONS: Metronomic treatment guided by positron-emission tomography could be a reasonable option in some high-risk pediatric tumours.

[Vitamin D as an important steroid hormone in breast cancer]. / Vitamin D jako významný steroidní hormon u karcinomu prsu.

Vitamin D is the third steroid hormone playing important bio-logical roles in the development of breast cancer. Decreased plasma levels of its 25- hydroxyderivative, 25OHD, display robust associations with higher incidence of breast cancer and shorter overall survival. Although no consensus exists, most authors agree that optimal plasma levels shall be within 75- 150 nmol/ l whereas levels higher than 375 nmol/ l can be potentially toxic with higher risk of hypercalcemia. To date, no data are available on the optimal levels of vitamin D related to the risk of breast cancer development, its phenotype features and the course of the disease. Published studies mostly describe associations among higher levels of 25OHD and lower bio-logically aggressiveness of the tumor. The polymorphism of VDR gene coding for the steroid receptor for vitamin Dmay be associated with higher disease incidence and also be of negative prognostic significance in breast cancer. This review presents an overall summary of the current knowledge and publications on vitamin D and breast cancer.