Philip H Cogen

Inactivation of the PTCH tumor suppressor gene occurs in a subset of sporadic medulloblastomas, suggesting that alterations in the PTCH pathway may be important in the development of this tumor. In order to address the frequency of genetic alterations affecting genes in this pathway, we used a combination of loss of heterozygosity (LOH) analysis, single-stranded conformational polymorphism (SSCP) analysis, and direct sequencing of DNA samples from sporadic primitive neuroectodermal ...

The best operative intervention for children with arachnoid cysts remains the subject of controversy. Recent reports stress that craniotomy for cyst fenestration is associated with a low incidence of morbidity and mortality and may leave the child shunt-independent. The cases of 40 pediatric patients with arachnoid cysts treated between 1978 and 1989 are reported. Five children with mild symptoms and small cysts that remained stable on follow-up studies have not required surgical ...

DNA methylation and epigenetic inactivation of the O6-methylguanine methyltransferase (MGMT) gene induces MGMT deficiency, reducing the tumor cell's DNA repair capacity and increasing its susceptibility to alkylating chemotherapeutic agents. Consequently, adult patients whose tumors are deficient in MGMT have better outcomes with alkylator chemotherapy, and MGMT methylation has been proposed as a screening marker of deficient tumors. In order to test the feasibility of this approach for ...

Ependymomas are glial tumors of the brain and spinal cord occurring both sporadically and in a familial syndrome, neurofibromatosis type 2 (NF2). Previous analyses performed on specimens obtained predominantly from adult patients have shown loss of DNA sequences from chromosome arm 22q, which is the location of the NF2 gene. Previously, we documented the consistent loss of chromosome arm 17p DNA in medulloblastoma and astrocytoma, which are the most common brain tumors in children. ...

Little is known about the genetic regulation of medulloblastoma dissemination, but metastatic medulloblastoma is highly associated with poor outcome. We obtained expression profiles of 23 primary medulloblastomas clinically designated as either metastatic (M+) or non-metastatic (M0) and identified 85 genes whose expression differed significantly between classes. Using a class prediction algorithm based on these genes and a leave-one-out approach, we assigned sample class to these tumors ...

Loss of heterozygosity for sequences located on chromosome 17p in several tumor types is often associated with mutations in the tumor suppressor gene p53. We previously showed consistent deletion of chromosome 17p12-13.1 in medulloblastoma, a common childhood brain tumor. Using denaturing gradient gel electrophoresis and direct sequencing, we have detected p53 mutations in only two of 20 medulloblastoma specimens. Moreover, additional RFLP studies of these 20 specimens showed loss of ...

Medulloblastoma is the most common childhood primary CNS tumor, and treatment approaches have evolved over the past three decades. The biologic underpinnings of medulloblastoma are not fully characterized, but recent work has identified new, important directions for research. Stratification of patients with medulloblastoma into risk groups is the backbone of most ongoing therapeutic studies. Patients are usually characterized as being either average risk or poor risk, although an ...

PURPOSE: To report the early results of hyperfractionated craniospinal radiation therapy with and without adjuvant chemotherapy for primitive neuroectodermal brain tumors (PNETs).

METHODS AND MATERIALS: Thirty-nine patients with PNETs were classified as good-risk (23) or poor-risk (16), based on postoperative magnetic resonance imaging and a cytological examination of cerebrospinal fluid. All patients received hyperfractionated craniospinal radiation therapy; poor-risk patients ...

In adults, loss of heterozygosity for DNA on 17p has been shown in high-grade anaplastic astrocytomas (AAs) and glioblastomas multiforme (GMs), and mutation of the TP53 tumor suppressor gene has been reported in all grades of astrocytomas. Little is known, however, about 17p deletion and TP53 mutation in juvenile pilocytic astrocytomas (JPAs), the most common low-grade tumors seen in children. To elucidate the genetic characteristics of pediatric high-grade astrocytomas and JPAs, we ...

Embryonal central nervous system (CNS) tumors are the most common group of malignant brain tumors in children. The diagnosis and classification of tumors belonging to this family have been controversial; however, utilization of molecular genetics is helping to refine traditional histopathologic and clinical classification schemes. Currently, this group of tumors includes medulloblastomas, supratentorial primitive neuroectodermal tumors, atypical teratoid/rhabdoid tumors, ...

Little is known about the risk of developing multicentric disease in patients with juvenile pilocytic astrocytoma (JPA), and even less about its prognosis. Only five cases have been reported. Between 1986 and 1992, the authors treated 90 patients with either primary or recurrent JPA, 11 of whom developed multicentric spread. Ten patients had primary tumors in the hypothalamic region, eight were under 4 years of age at initial diagnosis, all had initially undergone a subtotal resection or ...

Although primary intracranial neoplasms are the most common type of solid cancer in children, little is known about their etiology at the molecular genetic level. Recently, studies have shown that a class of genes known as tumor suppressors play an important role in the origin of several different types of human tumors, including those located in the central nervous system (CNS). Using a variety of techniques, selective loss of DNA sequences has been identified in tissue specimens from ...