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PubMed1999

The tanycytic ependymoma of the lateral ventricle: case report.

The tanycytic ependymoma is an extremely rare, primitive neuroectodermal tumor, arising from the ependymoglial cells or tanycytes. Such cells are generally seen in the primitive nervous system instead of the mature ependymal cells. The tanycytic ependymoma described in this report was found in a 42-year-old man. Histological analysis strongly suggested that this tumor originated from a primitive progenitor cell, the ependymoglia or the tanycyte in the lateral ventricle.

Adult↗
PubMed2006

Caveolin-1 (CAV1) is a target of EWS/FLI-1 and a key determinant of the oncogenic phenotype and tumorigenicity of Ewing's sarcoma cells.

Tumors of the Ewing's sarcoma family (ESFT), such as Ewing's sarcoma (EWS) and primitive neuroectodermal tumors (PNET), are highly aggressive malignancies predominantly affecting children and young adults. ESFT express chimeric transcription factors encoded by hybrid genes fusing the EWS gene with several ETS genes, most commonly FLI-1. EWS/FLI-1 proteins are responsible for the malignant phenotype of ESFT, but only few of their transcriptional targets are known. Using antisense and short hairpin RNA-mediated gene expression knockdown, array analyses, chromatin immunoprecipitation methods, and reexpression studies, we show that caveolin-1 (CAV1) is a new direct target of EWS/FLI-1 that is overexpressed in ESFT cell lines and tumor specimens and is necessary for ESFT tumorigenesis. CAV1 knockdown led to up-regulation of Snail and the concomitant loss of E-cadherin expression. Consistently, loss of CAV1 expression inhibited the anchorage-independent growth of EWS cells and markedly reduced the growth of EWS cell-derived tumors in nude mice xenografts, indicating that CAV1 promotes the malignant phenotype in EWS carcinogenesis. Reexpression of CAV1 or E-cadherin in CAV1 knockdown EWS cells rescued the oncogenic phenotype of the original EWS cells, showing that the CAV1/Snail/E-cadherin pathway plays a central role in the expression of the oncogenic transformation functions of EWS/FLI-1. Overall, these data identify CAV1 as a key determinant of the tumorigenicity of ESFT and imply that targeting CAV1 may allow the development of new molecular therapeutic strategies for ESFT patients.

Animals↗
PubMed2006

Ewing's sarcoma in the spinal nerve root: a case report and review of the literature.

Ewing's sarcoma (ES) is a highly malignant tumor composed of uniform small round cells. Recently, a single biologic entity, Ewing's sarcoma family of tumors (ESFT) has been accepted. The entity includes ES, extraskeletal Ewing's sarcoma (EES) and primitive neuroectodermal tumor (PNET). ESFT cells have immunoreactivity for CD99, an antigen determined by the MIC2 gene. Most ESFT has the (11;22) (q24;q12) translocation. The translocation results in the fusion of the EWS gene with the transcription factor gene FLI1 which has been considered a hallmark of ESFT. We present an extremely unusual case with ESFT in a spinal nerve root mimicking a neurogenic dumbbell tumor. A male aged 20 years noticed pain in his right buttock. Magnetic resonance imaging (MRI) revealed a mass in the right L5/S intervertebral foramen and the lesions in the sacrum. Surgery was performed with a presumptive diagnosis of a nerve sheath tumor. At surgery, the tumor was located in the right L5 nerve root sleeve. The sacral lesions were observed closely. At one month after surgery, radiologically multiple lesions were detected in the pelvic bones. Microscopically the lesions from the root and ilium were composed of small round cells immunoreactive for CD99. Reverse transcription-polymerase chain reaction detected transcripts resulting from the fusion of the EWS gene with FLI1 genes in the iliac lesion. Immunoreactivity for CD99 and detection of the EWS-FLI1 hybrid transcripts are important for the correct diagnosis of ESFT arising in an unusual location.

Adult↗
PubMed1997

Complications associated with intraventricular chemotherapy in patients with leptomeningeal metastases.

The authors studied complications associated with intraventricular chemotherapy in patients with leptomeningeal metastases (LM). One hundred twenty consecutive patients with LM (71 females and 49 males) ranging in age from 10 to 72 years (median 42 years) were treated with involved-field radiotherapy and intraventricular chemotherapy using an Ommaya reservoir and intraventricular catheter system. The diagnosis of LM was determined by a combination of clinical presentation (114 patients); cerebrospinal fluid cytological studies (100); or neuroradiographic studies (42). Systemic tumor histological findings included breast (34 patients); non-Hodgkin's lymphoma (22); melanoma (16); primitive neuroectodermal tumors including medulloblastoma (10); glial neoplasms, leukemia, small cell lung, nonsmall cell lung, and colon (six each); prostate and kidney (three each); and gastric cancers (two). Sixteen patients, all with non-Hodgkin's lymphoma, also had acquired immune deficiency syndrome. Patients received one to four (median two) chemotherapeutic drugs and underwent a total of 1110 cycles of intraventricular chemotherapy (median 10). Intraventricular chemotherapy administration and diagnostic Ommaya reservoir punctures totaled 4400, with a median of 46 per patient. Complications included aseptic/chemical meningitis (52 patients); myelosuppression due to intraventricular chemotherapy (21); catheter-related infections (nine); unidirectional catheter obstruction (six); intraventricular catheter malpositioning (two); Ommaya reservoir exposure (two); leukoencephalopathy (two); and chemotherapy-related myelopathy (one). There were no treatment-related deaths; however, seven patients (6%) required additional surgery for either catheter repositioning (two) or reservoir removal (five). Seven patients with catheter-related infections were treated successfully with intraventricular and systemic antibiotic drugs, thereby preserving the Ommaya system. The authors conclude that Ommaya reservoirs are convenient and pharmacologically rational systems for administering intraventricular chemotherapy. Overall, serious complications requiring surgery are infrequent (6%) and most often secondary to catheter infections, Ommaya reservoir exposure, or initial catheter malpositioning. In the majority of instances, catheter infections may be managed medically, as may the most common complications of intraventricular chemotherapy including aseptic meningitis (43% of patients) and myelosuppression (18%).

Adolescent↗
PubMedDate not supplied

Rhabdoid glioblastoma.

Rhabdoid phenotypic change has been described in a number of different neoplasms from diverse organ sites. These tumors share common light and electron-microscopic features, display a polyphenotypic immunohistochemical profile and often show cytogenetic abnormalities of chromosome 22. In the central nervous system (CNS), most rhabdoid tumors occur in the posterior fossa of very young children and are associated with a primitive neuroectodermal tumor (PNET) component and are designated atypical teratoid/rhabdoid tumors. Infrequently, other rhabdoid tumors of the CNS have been described, including rhabdoid meningiomas and malignant rhabdoid tumors of uncertain histogenesis. Several examples of conventional gliomas displaying significant areas with rhabdoid morphology were also presented in an abstract by Kepes and Moral [1991], although never published in final manuscript form. We now detail the case of an 18-year-old male with an aggressive, supratentorial CNS rhabdoid tumor that was associated with an epithelioid glioblastoma and apparently arose from areas of low-grade glioma. The rhabdoid tumor component was present in the original tumor but became more predominant with each of 3 successive resections. No areas of PNET were identified. Electron microscopy and immunohistochemistry showed features classic for rhabdoid tumors and cytogenetic studies demonstrated multiple tumor clones with monosomy 22. This case documents progressive rhabdoid transformation of a glioma, expands the spectrum of CNS tumor types that can display a rhabdoid phenotype and highlights the diagnostic and therapeutic challenges with this type of tumor.

Adolescent↗
PubMed2004

[Experience and discussion on treatment of high-grade soft tissue sarcomas of crura in youth].

OBJECTIVE: To summarize the experience and investigate better method on treatment of high-grade soft tissue sarcomas of crura in youth. METHODS: Six young cases suffered from high-grade soft tissue sarcomas of crura were treated by interpolatory chemotherapy using vindesine 4mg or vincristine 2 mg combined with cisplatin 40 - 60 mg and 4'-Epidoxorubicin (4'-epi-ADM) 50 - 80 mg. There were 3 males and 3 females, and their ages rang from 12 to 23. The primary tumor locations were: calf in 4, thigh in 1, popliteal fossa in 1. The pathological type of these 6 cases were: 1 small round cell tumor from soft tissue, one rabdomyosarcoma, one alveoliar soft part sarcoma, one synovial sarcoma, one primitive neuroectodermal tumor and one without classification. All cases received interpolatory chemotherapy twice. Before their receiving interpolatory chemotherapy they had no tumor metastases. The maximum diameters of tumors rang from 4 - 15 cm. One patient's tumor disappeared after interpolatory chemotherapy and she received no further therapy. The other 5 cases received operations and one of them received additional pre-operational radiotherapy using Co(60) and pre-operational systemic chemotherapy using ifosfamide and dacarbazine. RESULTS: The tumors dwindled in size of 1 - 8 cm after interpolatory chemotherapy. All cases saved their crura and had normal functions. After interpolatory chemotherapy, all patients suffered from edema and ache of crura. One patient suffered from lymphatitis. All these patients were followed up for 6 - 20 months. All of them were alive and had pigmentations on their crura. A lung metastasis was found in 1 patient by CT 2 months after surgery, then he was in hospital and treated by chemotherapy. CONCLUSIONS: For treatment of high-grade soft tissue sarcomas of crura which are difficult to resect in youth, interpolatory chemotherapy is a good choice.

Adolescent↗
PubMed1987

Phase II trial of ifosfamide in children with malignant solid tumors.

Ifosfamide was given to 61 patients with malignant solid tumors diagnosed before the age of 21 years. In this phase II study, all patients received 1.6 g/m2/day X 5 iv over 15 minutes followed by mesna at a dose of 400 mg/m2 iv at 15 minutes and 4 and 6 hours after ifosfamide. Responses were observed in five of 15 patients with osteosarcoma, two of ten with neuroblastoma, two of six with Wilms' tumor, two of five with rhabdomyosarcoma, four of eight with other soft tissue sarcomas, one of one with retinoblastoma, one of two with germ cell tumors, one of one with B-cell lymphoma, and one of one with a primitive neuroectodermal tumor. Fifty-nine of 61 patients had received prior alkylating agent therapy which included cyclophosphamide, cisplatin, mechlorethamine, melphalan, or dacarbazine. Fourteen of 19 responses developed in patients whose tumors were resistant to treatment with cyclophosphamide. A patient with malignant Schwannoma who had received no prior chemotherapy developed a complete response which lasted 12 months. A patient with brain metastases of osteosarcoma has had complete response for greater than 2 years. Complete response was also observed in a patient with B-cell lymphoma. Toxicity consisted of mild to moderate nausea and vomiting, transient reversible myelosuppression, occasional elevation of serum BUN or creatinine, and transient neurotoxicity characterized by somnolence, confusion, weakness, tremor, hallucinations, or seizures. We conclude that ifosfamide is an important alkylating agent without apparent complete cross-resistance with cyclophosphamide, and as such should be further investigated for determination of its activity in patients with pediatric neoplasms and considered for incorporation into phase II-III trials for certain tumors.

Adolescent↗
PubMed1984

Surface topography and extent of invasiveness of SV40 virus-transformed hamster brain cells and transformed cell-produced tumors.

Scanning electron microscopy (SEM) was used to study the surface configuration of SV40 virus-transformed 1 day old Syrian hamster brain cells and transformed cell-produced tumors and the alterations in cell membrane configuration that become evident with the development of invasiveness. Cell cultures of dissociated cerebral cortex, brain-stem, cerebellar vermis and cerebellar hemisphere were transformed to a neoplastic state with SV40 virus. The transformed cells were then inoculated intracerebrally into hamsters to produce intracranial tumors, and cell cultures were obtained from these tumors. Invasiveness was determined by reinoculating the transformed or tumor cells intracerebrally into hamsters and examining histological sections of the resulting tumors. Cultures of the transformed and tumor cells were also critical point dried and studied with SEM. Tumors of cerebral cortex and brainstem derivation (Group I) had the histological appearance of astrocytomas and were invasive for adjacent normal brain. With SEM, they were flat, epithelioid, and surrounded by ruffles and microvilli. They grew only in monolayers and showed few of the rounded forms with blebs and/or microvilli typical of mitosis. Tumors of cerebellar vermis and cerebellar hemisphere derivation (Group II) had the histological appearance of primitive neuroectodermal tumors and were not invasive. With SEM, they were more rounded, fusiform or stellate, and lacked surface specializations at their borders. They exhibited multilayered growth and the rounded forms associated with mitosis. Tumor cells of both groups had more surface activity than transformed cells. These observations give some support to the concept that a decrease in contact inhibition of locomotion and an increase in density-dependent inhibition of locomotion and in mobilization are essential for the development of invasiveness in tumors.

Animals↗
PubMed1995

MR and cognitive testing of patients undergoing osmotic blood-brain barrier disruption with intraarterial chemotherapy.

PURPOSE: To determine whether osmotic blood-brain barrier disruption is associated with MR abnormalities or cognitive deterioration and, if so, whether the MR findings correlate with cognitive test results. METHODS: Fifteen brain tumor patients who had a complete tumor response (nine central nervous system lymphoma, three germ cell and two astrocytoma, and one primitive neuroectodermal tumor) treated with blood-brain barrier disruption procedures (318 total procedures) with intraarterial chemotherapy were included. MR images were evaluated for the development of white matter hyperintensity, vascular lesions, or atrophy. Cognitive testing was performed to assess deterioration caused by this therapy. RESULTS: In two patients white matter hyperintensity developed, in two small vascular lesions developed, and in one mild atrophy developed. One infarct was asymptomatic and the second one resulted in mild dysesthesia in one upper extremity. No patient showed diminished cognitive function on the posttherapy evaluation. CONCLUSION: In patients undergoing blood-brain barrier disruption with intraarterial chemotherapy, new abnormalities on MR imaging may develop. These patients maintain the same level of cognitive and neurologic function and MR findings do not correlate with the results of cognitive testing.

Adolescent↗
PubMed1984

Malignant neoplasm of mixed mesenchymal and neuroepithelial origin (ectomesenchymoma) of thigh.

A 49-year-old man had a malignant soft tissue tumor of the right thigh with metastasis to the femoral region and lower quadrant of the anterior abdominal wall on the right side and the left supraclavicular lymph nodes. The neoplasm showed features of chondrosarcoma and primitive neuroectodermal tumor (combined neuroblastoma, ependymoma, astrocytoma, and oligodendroglioma). The gliomatous part of the mixed tumor was confirmed by identification of the glial fibrillary acidic protein (GFAP). The diverse cellular population suggests a tumor origin from the ectomesenchymal remnant of the neural crest. The mesenchymal component of the neural crest would differentiate into the chondrosarcoma and the neuroectodermal component into the primitive neuroectodermal neoplasm. These various neoplastic elements, then, would form a neoplasm of mixed mesenchymal and neuroepithelial origin or an ectomesenchymoma.

Astrocytoma↗
PubMed1990

A new rat brain tumor model: glioma disseminated via the cerebral spinal fluid pathways.

A rat brain tumor model has been developed with the clinical and pathological features of dissemination via the cerebral spinal fluid (CSF) pathways. A precise number of 9L gliosarcoma cells (5 x 10(2) to 5 x 10(5)) is stereotactically injected into the CSF of the lateral ventricle. The interval until the onset of neurological symptoms and then death is reproducible and dependent upon the number of cells injected. The median survival of three groups of rats receiving 5 x 10(5) cells in three different experiments was 17, 18 and 19 days respectively. For three groups receiving 5 x 10(4) cells, the median survival was 23, 24 and 25.5 days respectively and for two groups receiving 5 x 10(3) cells the median survival was 28 and 30 days respectively. The animals developed multiple tumor implants along the CSF pathways usually resulting in hydrocephalus. This tumor model was developed to simulate dissemination via CSF pathways as seen with medulloblastoma and other primitive neuroectodermal tumors of the central nervous system. It will be used to evaluate the therapeutic efficacy of intraventricularly administered anti-neoplastic drugs against small implants and malignant cells in the CSF pathways.

Animals↗
PubMed2002

PCNA and Ki-67 in central nervous system tumors: correlation with the histological type and grade.

Determination of proteins in the control of proliferation in normal cells helps a better understanding of cellular transformation and proliferation mechanisms. Measurement of proliferative activity is important in determining the tumor grade, recurrence span and malignancy. Proliferating cell nuclear antigen (PCNA) and Ki-67 are two of the nuclear markers used to demonstrate the proliferative phase of the cell cycle. In the present study, 63 central nervous system (CNS) tumors of various histologic types, diagnosed in Cukurova University Medical Faculty. Department of Pathology and graded according to WHO grading system were examined for PCNA and Ki-67 monoclonal antibodies using immunohistochemistry. Results were analyzed with statistical methods. Distribution of PCNA and Ki-67 LI (labeling index) values were determined for different tumor types. The highest PCNA and Ki-67 LI values were detected in medulloblastoma, malignant meningioma, primitive neuroectodermal tumor (PNET) and glioblastoma (GBM) groups, while pilocytic astrocytoma, meningioma, craniopharyngioma and oligodendroglioma showed the lowest values. In such tumors, the correlation between the increasing grade and PCNA and Ki-67 LI values were statistically significant. A correlation between the clinical outcome and Ki-67 and PCNA LI values was also detected. Conclusively, both markers can be used to evaluate the tumor grade and to asses the possibility of recurrence and malignancy in CNS tumors.

Astrocytoma↗
PubMed2006

Irinotecan for children with relapsed solid tumors.

Irinotecan is expected to become a new drug for childhood solid tumors. Sixteen children with relapsed solid tumors received irinotecan 180 mg/m2/day for 3 consecutive days, repeated once after 25 days off. Their original tumors were neuroblastoma in 7, rhabdomyosarcoma in 3, nephroblastoma and undifferentiated sarcoma in 2 each, and primitive neuroectodermal tumor and leiomyosarcoma in 1 each. The average age at trials was 6 years. Partial response was achieved in 5 (31.3%) (neuro-blastoma, rhabdomyosarcoma, nephroblastoma, undifferentiated sarcoma, and leiomyosarcoma), and decrease in tumor marker in the other 2. Irinotecan appears promising, and could become included in the first-line treatment.

Camptothecin↗
PubMedDate not supplied

Canine intracranial primary neoplasia: 173 cases (1986-2003).

This study investigates the clinical and pathologic findings associated with 173 primary brain tumors in our hospital population of dogs that presented between the years 1986 and 2002. Of the 173 primary brain tumors, 78 (45%) were meningiomas, 29 (17%) were astrocytomas, 25 (14%) were oligodendrogliomas, 12 (7%) were choroid plexus tumors, and 7 (4%) were primary central nervous system lymphomas. Smaller numbers of glioblastomas (n = 5), primitive neuroectodermal tumors (n = 5), histiocytic sarcomas (n = 5), vascular hamartomas (n = 4), and unclassified gliomas (n = 3) were identified. One dog had both a meningioma and an astrocytoma. Most tumors were located within the telencephalon, and seizures were the most common clinical presenting complaint. Of 168 tumors for which a location in the brain was recorded at postmortem examination, 79 were found to involve more than 1 brain division. Other neoplasms unrelated to the primary brain tumor were identified on postmortem examination in 39 dogs (23%). Intrathoracic and intraabdominal neoplasms were present at necropsy in 13 and 24 cases, respectively. Based on the results of this study, thoracic radiographs and abdominal ultrasonography may be indicated to look for extracranial neoplasia prior to advanced imaging of the brain or intracranial surgery.

Animals↗
PubMed1993

In-vivo proliferative potential of primary human brain tumors; its correlation with histological classification and morphological features: II. Nonglial tumors.

In-vivo cell kinetics study following peroperative intravenous infusion of bromodeoxyuridine (BrdU) was done in 10 cases of primitive neuroectodermal tumors (PNET) and 44 nonglial tumors of different histological types. The histological features usually regarded as indicators of aggressive behaviour were examined in these tumors and correlated with in-vivo labelling index (LI). In the case of meningiomas, increased cellularity, pleomorphism and mitosis had no correlation with LI. Benign non-recurrent meningiomas usually showed LI < or = 1% (mean 0.6 +/- 0.3%) whereas recurrent and malignant meningioma showed higher LI (mean 2.6 +/- 0.5% and 2.8 +/- 0.4% respectively). Follow-up study suggested that meningiomas having benign histological appearance with LI > 1% might have increased chance of recurrence. In cases of PNETs among different histological features, mitosis and differentiation seemed to be related to the biological behaviour. Astrocytic differentiation was associated with lower rate of proliferation. In pituitary adenomas different hormone producing and null cell adenomas showed similar low proliferative potential (0.6 +/- 0.3%). Benign nerve sheath tumors, craniopharyngioma and choroid plexus papilloma showed low in-vivo LI of less than 1%. Thus the present study revealed the inadequacies of routine histological examination in assessing the aggressiveness of the nonglial tumors, especially meningiomas. In-vivo LI may be a good supplement to histological diagnosis as well as helping to assess the prognosis and accordingly the management of individual cases.

Adolescent↗
PubMed2005

The results of surgical treatment of chest wall tumors in childhood.

Chest wall tumors (CWT) are rarely seen in childhood and surgery constitutes a complementary part of the therapy. The early and late results of CWT resection and chest wall reconstruction were evaluated retrospectively. The children who underwent chest wall resection for CWT between January 1990 and November 2003 were evaluated retrospectively. Seventeen children (male/female = 12/5, mean age: 7.58 years) underwent chest wall resection for CWT. Fifteen patients underwent initial biopsy (tru-cut, n = 8 or open biopsy, n = 7) and two underwent initial resection. The diagnosis was malignant tumor in 12 (70%) and benign in 5 (30%). They were Ewing's sarcoma (ES) (n = 4), primitive neuroectodermal tumor (PNET) (n = 3), Askin's tumor (n = 1), rhabdomyosarcoma (RMS) (n = 2), neuroblastoma (n = 2), osteochondroma (n = 1), aneurysmal bone cyst (n = 2) and hamartoma (n = 2). Preoperative chemotherapy was given to most patients with malignant tumor. All patients had only local tumor at the time of resection. Thoracotomy was performed in all patients. All tumor tissues with the affected rib/ribs were resected en bloc with the adjacent tissues. The number of resected ribs was 1 (n = 6), 2 (n = 7) and 3 (n = 4). Chest wall defects were repaired primarily (n = 8) or with grafts (n = 9). Dura (n = 4), Neuro-patch (n = 3) and Goretex (n = 2) were used for closure. Wound infection and pleural fistula occurred in one patient. Patients with benign tumor were free of complaints or complications during follow up. All patients with malignant tumor received postoperative chemotherapy. Local recurrence did not occur in all patients. Five patients developed distant metastasis and two died. Scoliosis was encountered in one patient during follow-up. Since most of the CWT are malignant and not initially suitable for surgical excision, the management includes tissue diagnosis either by tru-cut or open biopsy. Determination of malignant condition should be followed by an intensive chemotherapy. Chest wall resection is planned to control local disease. Chest wall reconstruction may be needed for large defects following resection of CWT. Prosthetic materials can be used safely. Early complications of the surgery are limited. The patients should be closely followed up for late complications such as scoliosis, restrictive pulmonary disease and for the development of metastasis, which is a part of natural course of malignant CWT in children.

Adolescent↗
PubMed2005

Cyclin D1 is overexpressed in atypical teratoid/rhabdoid tumor with hSNF5/INI1 gene inactivation.

OBJECT: Although atypical teratoid/rhabdoid tumor (AT/RT) is known to generate through inactivation of the hSNF5/INI1 gene on chromosome 22q, the downstream molecular mechanism remains unclear. We histologically and molecularly reviewed our pediatric brain tumors for unrecognized AT/RTs and evaluated the role of cyclin D1, a potential molecular target of hSNF5/INI1. METHODS: We analyzed 16 tumors under three years of age: seven medulloblastomas, three anaplastic ependymomas (E IIIs), two each of supratentorial primitive neuroectodermal tumors (sPNETs) and choroid plexus carcinomas (CPCs), and one each of neuroblastoma and pineoblastoma. Immunohistochemistry for glial fibrillary acidic protein, vimentin, epithelial membrane antigen, smooth muscle actin and cyclin D1 was performed. Polymerase chain reaction (PCR)-single-strand conformation polymorphism analysis with direct sequencing, differential PCR and microsatellite analysis were conducted for hSNF5/INI1mutation, homozygous deletion and loss of heterozygosity (LOH) on 22q, respectively. Because of the presence of rhabdoid cells and the polyimmunophenotypic features, the diagnosis was revised to AT/RT in five (31%) tumors, namely, two E IIIs and one each of medulloblastoma, CPC and pineoblastoma. Three of them harbored such hSNF5/INI1 aberrations as germline single base deletion (492/6 delC) and missense mutation (C157T) together with LOH 22q or homozygous deletion. Cyclin D1 was overexpressed in those three tumors but not in the two that lacked hSNF5/INI1 inactivation. CONCLUSION: AT/RT can be misdiagnosed as a variety of tumors, including ependymoma that potentially harbors LOH 22q. Our data indicate that cyclin D1 is a target of hSNF5/INI1in primary tumors.

Central Nervous System Neoplasms↗
PubMed1999

Spectrum of hSNF5/INI1 somatic mutations in human cancer and genotype-phenotype correlations.

The hSNF5/INI1 gene which encodes a member of the SWI/SNF chromatin ATP-dependent remodeling complex, is a new tumor suppressor gene localized on chromosome 22q11.2 and recently shown to be mutated in malignant rhabdoid tumors. We have searched for hSNF5/INI1 mutations in 229 tumors of various origins using a screening method based on denaturing high-performance liquid chromatography. A total of 31 homozygous deletions and 36 point alterations were identified. Point mutations were scattered along the coding sequence and included 15 nonsense, 15 frameshift, three splice site, two missense and one editing mutations. Mutations were retrieved in most rhabdoid tumors, whatever their sites of occurrence, indicating the common pathogenetic origin of these tumors. Recurrent hSNF5/INI1 alterations were also observed in choroid plexus carcinomas and in a subset of central primitive neuroectodermal tumors (cPNETs) and medulloblastomas. In contrast, hSNF5/INI1 point mutations were not detected in breast cancers, Wilms' tumors, gliomas, ependymomas, sarcomas and other tumor types, even though most analyzed cases harbored loss of heterozygosity at 22q11.2 loci. These results suggest that rhabdoid tumors, choroid plexus carcinomas and a subset of medulloblastomas and cPNETs share common pathways of oncogenesis related to hSNF5/INI1 alteration and that hSNF5/INI1 mutations define a genetically homogeneous family of highly aggressive cancers mainly occurring in young children and frequently, but not always, exhibiting a rhabdoid phenotype.

Chromatography, High Pressure Liquid↗