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Cancer Types / Pediatric Cancers / Retinoblastoma / NCI Resources

NCI CANCERLIT^® Search: Retinoblastoma Gene (RB) - October 2001

National Cancer Institute^®
Last Modified: November 21, 2001

The retinoblastoma protein acts as a transcriptional coactivator required for osteogenic differentiation.

Primary and secondary glioblastomas: from concept to clinical diagnosis.

Roles of the functional loss of p53 and other genes in astrocytoma tumorigenesis and progression.

Table of Contents

1
UI - 21431978
AU - Thomas DM; Carty SA; Piscopo DM; Lee JS; Wang WF; Forrester WC; Hinds PW
TI - The retinoblastoma protein acts as a transcriptional coactivator required for osteogenic differentiation.
SO - Mol Cell 2001 Aug;8(2):303-16
AD - Department of Pathology and, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
The incidence of osteosarcoma is increased 500-fold in patients who inherit mutations in the RB gene. To understand why the retinoblastoma protein (pRb) is specifically targeted in osteosarcoma, we studied its function in osteogenesis. Loss of pRb but not p107 or p130 blocks late osteoblast differentiation. pRb physically interacts with the osteoblast transcription factor, CBFA1, and associates with osteoblast-specific promoters in vivo in a CBFA1-dependent fashion. Association of pRb with CBFA1 and promoter sequences results in synergistic transactivation of an osteoblast-specific reporter. This transactivation function is lost in tumor-derived pRb mutants, underscoring a potential role in tumor suppression. Thus, pRb functions as a direct transcriptional coactivator promoting osteoblast differentiation, which may contribute to the targeting of pRb in osteosarcoma.

2
UI - 21435046
AU - Kleihues P; Ohgaki H
TI - Primary and secondary glioblastomas: from concept to clinical diagnosis.
SO - Neuro-oncol 1999 Jan;1(1):44-51
AD - International Agency for Research on Cancer (IARC), World Health Organization (WHO), Lyon, France.
Glioblastomas may develop de novo (primary glioblastomas) or through progression from low-grade or anaplastic astrocytomas, (secondary glioblastomas). These subtypes of glioblastoma constitute distinct disease entities that evolve through different genetic pathways, affect patients at different ages, and are likely to differ in prognosis and response to therapy. Primary glioblastomas develop in older patients and typically show EGFR overexpression, PTEN (MMAC1) mutations, CDKN2A (p16) deletions, and less frequently, MDM2 amplification. Secondary glioblastomas develop in younger patients and often contain TP53 mutations as the earliest detectable alteration. These characteristics are derived largely from patients selected on the basis of clinical history and sequential biopsies. Currently available data are insufficient for a substitution of histologic classification and grading of astrocytic tumors by genetic typing alone. More subtypes of glioblastomas may exist with intermediate clinical and genetic profiles, a factor exemplified by the giant-cell glioblastoma that clinically and genetically occupies a hybrid position between primary (de novo) and secondary glioblastomas. Future research should aim at the identification of criteria for a combined clinical, histologic, and genetic classification of astrocytic tumors.

3
UI - 21435054
AU - Nozaki M; Tada M; Kobayashi H; Zhang CL; Sawamura Y; Abe H; Ishii N; Van
TI - Meir EG Roles of the functional loss of p53 and other genes in astrocytoma tumorigenesis and progression.
SO - Neuro-oncol 1999 Apr;1(2):124-37
AD - Department of Neurosurgery, Cancer Institute, Hokkaido University School of Medicine, Kitaku, Sapporo 060-8638, Japan.
Loss of function of the p53 tumor suppressor gene due to mutation occurs early in astrocytoma tumorigenesis in about 30-40% of cases. This is believed to confer a growth advantage to the cells, allowing them to clonally expand due to loss of the p53-controlled G1 checkpoint and apoptosis. Genetic instability due to the impaired ability of p53 to mediate DNA damage repair further facilitates the acquisition of new genetic abnormalities, leading to malignant progression of an astrocytoma into anaplastic astrocytoma. This is reflected by a high rate of p53 mutation (60-70%) in anaplastic astrocytomas. The cell cycle control gets further compromised in astrocytoma by alterations in one of the G1/S transition control genes, either loss of the p16/CDKN2 or RB genes or amplification of the cyclin D gene. The final progression process leading to glioblastoma multiforme seems to need additional genetic abnormalities in the long arm of chromosome 10; one of which is deletion and/or functional loss of the PTEN/MMAC1 gene. Glioblastomas also occur as primary (de novo) lesions in patients of older age, without p53 gene loss but with amplification of the epidermal growth factor receptor (EGFR) genes. In contrast to the secondary glioblastomas that evolve from astrocytoma cells with p53 mutations in younger patients, primary glioblastomas seem to be resistant to radiation therapy and thus show a poorer prognosis. The evaluation and design of therapeutic modalities aimed at preventing malignant progression of astrocytomas and glioblastomas should now be based on stratifying patients with astrocytic tumors according to their genetic diagnosis.

The above citations and abstracts reflect those newly added to CANCERLIT for the month and topic listed in the title. The citations have been retrieved from CANCERLIT using a predefined search strategy of indexed subject terms. Although the search strategy has been refined as best as possible, citations may appear that are not directly related to the topic, and occasionally relevant references may be omitted.

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