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Abramson Cancer CenterNCI CANCERLIT® Search: Retinoblastoma Gene (RB) - January 2002
National Cancer Institute®
Last Modified: January 1, 2002
Table of Contents
1
UI - 11406530
AU - Paggi MG; Giordano A
TI -
Who is the boss in the retinoblastoma family? The point of view of
Rb2/p130, the little brother.
SO - Cancer Res 2001 Jun 15;61(12):4651-4
AD - Laboratory of Cell Metabolism and Pharmacokinetics, Center for
Experimental Research, Regina Elena Cancer Institute, 00158 Rome, Italy.
paggi@ifo.it
This review portrays an updated overview about the possible tumor
suppressive properties of the Rb2/p130 gene, the third member of the
retinoblastoma (RB) family of genes, including RB itself and p107. After
a brief analysis of the established structural and functional
similarities among the three genes, the main purpose is to critically
analyze present evidence whether Rb2/p130 shares the role of a tumor
suppressor. Taking into account the well-proven growth suppressive
properties of Rb2/p130 and p107, we discuss the analysis of mutated or
deleted forms of Rb2/p130 found in a number of human cancers. Finally,
we take into consideration the data provided by the targeted disruption
of each RB family gene, alone or in combination, in the mouse model.
2
UI - 11447760
AU - Morris EJ; Dyson NJ
TI -
Retinoblastoma protein partners.
SO - Adv Cancer Res 2001;82():1-54
AD - Laboratory of Molecular Oncology, Massachusetts General Hospital Cancer
Center, Charlestown, Massachusetts 02129, USA.
Studies of the retinoblastoma gene (Rb) have shown that its protein
product (pRb) acts to restrict cell proliferation, inhibit apoptosis,
and promote cell differentiation. The frequent mutation of the Rb gene,
and the functional inactivation of pRb in tumor cells, have spurred
interest in the mechanism of pRb action. Recently, much attention has
focused on pRb's role in the regulation of the E2F transcription factor.
However, biochemical studies have suggested that E2F is only one of many
pRb-targets and, to date, at least 110 cellular proteins have been
reported to associate with pRb. The plethora of pRb-binding proteins
raises several important questions. How many functions does pRb possess,
which of these functions are important for development, and which
contribute to tumor suppression? The goal of this review is to summarize
the current literature of pRb-associated proteins.
3
UI - 11584300
AU - Sherr CJ
TI -
The INK4a/ARF network in tumour suppression.
SO - Nat Rev Mol Cell Biol 2001 Oct;2(10):731-7
AD - Department of Tumor Cell Biology, Howard Hughes Medical Institute, St
Jude Children's Research Hospital, 332 North Lauderdale, Memphis,
Tennessee 38105, USA. sherr@stjude.org
The retinoblastoma protein (RB) and p53 transcription factor are
regulated by two distinct proteins that are encoded by the INK4a/ARF
locus. Genes encoding these four tumour suppressors are disabled, either
in whole or in part, in most human cancers. A complex signalling network
that interconnects the activities of RB and p53 monitors oncogenic
stimuli to provide a cell-autonomous mode of tumour surveillance.
4
UI - 11704837
AU - Robinson GW; Wagner KU; Hennighausen L
TI -
Functional mammary gland development and oncogene-induced tumor
formation are not affected by the absence of the retinoblastoma gene.
SO - Oncogene 2001 Oct 25;20(48):7115-9
AD - Laboratory of Genetics and Physiology, National Institute of Diabetes
and Digestive and Kidney Diseases, National Institutes of Health,
Bethesda, Maryland, MD 20892, USA. gertraur@bdg10.niddk.nih.gov
Loss of cell cycle regulation in mammary epithelium results in impaired
mammary gland development and neoplasia. We investigated the
consequences of the absence of pRb in mammary epithelial cells during
normal development and in mice that express an oncogene in the mammary
epithelium. Since pRb-deficiency results in embryonic lethality, we
transplanted pRb-null mammary anlagen into wild hosts. pRb-deficient
mammary epithelia were capable of functional differentiation in term
animals and they regenerated a differentiated gland even after multiple
pregnancies. In serial transplantations no significant differences were
found in outgrowth of pRb-deficient and wild type epithelia indicating
that the absence of pRb does not lead to transformation. Likewise the
effect of a TGFbeta1 transgene was not altered in the absence of pRb.
The susceptibility of mammary epithelium to form tumors was assessed in
three different models. No differences in tumor incidence were found
between wild type and Rb +/- WAP-int3, MMTV-PyMT transgenic and Brcal-/-
epithelia. These results demonstrate that the absence of pRb does not
affect normal mammary gland development and tumorigenesis in three
different mouse models investigated and suggest that loss of more than
one member of the pRb pathway is required to induce mammary tumors.
5
UI - 11676855
AU - Sakajiri S; Kawamata N; Egashira M; Mori K; Oshimi K
TI -
Molecular analysis of tumor suppressor genes, Rb, p53, p16INK4A,
p15INK4B and p14ARF in natural killer cell neoplasms.
SO - Jpn J Cancer Res 2001 Oct;92(10):1048-56
AD - Division of Hematology, Department of Medicine, Juntendo University
School of Medicine, Bunkyo-ku, Tokyo 113-8421.
Natural killer (NK) cell neoplasms, which are derived from mature or
precursor NK cells, are rare diseases and are observed predominantly in
Asian countries. We analyzed the status of the Rb, p53, p15INK4B,
p16INK4A and p14ARF genes in these diseases by Southern blot, polymerase
chain reaction-single strand conformational polymorphism (PCR-SSCP) and
western blot analysis. We used 31 NK cell neoplasms, including four cell
lines derived from NK cell neoplasms, 3 myeloid / NK cell precursor
acute leukemias, 4 blastic NK cell lymphoma / leukemias, 4 aggressive NK
cell leukemia / lymphomas, 4 nasal NK cell lymphomas, and 12 chronic NK
lymphocytosis. We found gene amplification of the p53 gene in one nasal
NK cell lymphoma, and point mutations of the p53 gene in one blastic NK
cell lymphoma / leukemia and one chronic NK lymphocytosis. In addition,
homozygous deletions of p15, p16 and p14 genes in 5 out of 31 samples
were detected; 3 were from nasal NK cell lymphoma and 2 from blastic NK
cell lymphoma / leukemia. Also hemizygous deletion of the Rb gene in one
blastic NK cell lymphoma was detected. Rb proteins were highly expressed
in one cell line as well as two myeloid / NK cell precursor acute
leukemias. In other cell lines, complete loss and an aberrant migration
pattern of Rb protein expression were observed. Comparative genomic
hybridization suggested that the homozygous deletions of the p15, p16
and p14 were subtle chromosomal deletions and could not be identified by
standard karyotyping in some cases. Although the number of cases we
analyzed was not large, alterations identified in the Rb, p53, p16, p15
and p14 genes are of significance and might be associated with
tumorigenesis in NK cell neoplasms.
6
UI - 11781822
AU - Lefevre SH; Vogt N; Dutrillaux AM; Chauveinc L; Stoppa-Lyonnet D; Doz F;
TI -
Desjardins L; Dutrillaux B; Chevillard S; Malfoy B
Genome instability in secondary solid tumors developing after
radiotherapy of bilateral retinoblastoma.
SO - Oncogene 2001 Dec 6;20(56):8092-9
AD - Institut Curie - CNRS UMR 147, 26 rue d'Ulm, 75248 Paris Cedex 05,
France.
Genome alterations of seven secondary tumors (five osteosarcomas, one
malignant peripheral sheath nerve tumor, one leiomyosarcoma) occurring
in the field of irradiation of patients treated for bilateral
retinoblastoma have been studied. These patients were predisposed to
develop radiation-induced tumors because of the presence of a germ line
mutation in the retinoblastoma gene (RB1). Tumor cells were
characterized by a high chromosome instability whereas microsatellites
and minisatellites were found to be stable. In all tumors, the normal
RB1 allele was lost with the corresponding chromosome 13, whereas the
germ line mutated allele was retained. The two alleles of TP53 were
inactivated, one by deletion of the short arm of chromosome 17, the
other by mutation. As compared with non-radiation-induced tumors, the
observed panel of TP53 mutations was uncommon with sites not recurrently
found otherwise and a high rate of deletions (3/7). In these predisposed
patients, the loss of the single normal allele of RB1 is rather due to
the radiation-induced chromosome instability than a direct effect of
ionizing radiation.
7
UI - 8400245
AU - Juliusson G; Gahrton G; Einhorn S; Liu Y; Oscier DG; Chapman R
TI -
Chromosome abnormalities and RB1 gene deletions in chronic lymphocytic
leukemia.
SO - Blood 1993 Sep 15;82(6):1938-9
8
UI - 8279785
AU - Klijn JG; Berns PM; Bontenbal M; Foekens JA
TI -
Growth factors. Clinical implications in breast cancer.
SO - Ann N Y Acad Sci 1993 Nov 30;698():85-101
AD - Department of Medical Oncology, Rotterdam Cancer Institute, The
Netherlands.
9
UI - 2562179
AU - Hastie ND; Bickmore W; Pritchard-Jones K; Porteous DJ; van Heyningen V
TI -
Wilms tumour: a developmental anomaly.
SO - Princess Takamatsu Symp 1989;20():145-50
AD - MRC Human Genetics Unit, Western General Hospital, Edinburgh, U.K.
Wilms tumour (WT) is a developmental anomaly of the kidney which results
from loss of function of at least one so called tumour suppressor gene
on chromosome 11. The position of the gene at chromosome 11p13 is known
through the association of WT with aniridia (lack of an iris), mental
retardation and genitourinary abnormalities in the WAGR syndrome. Here
we discuss the high resolution mapping studies to locate the position of
the gene and conclude that the gonadal abnormalities in WAGR patients
may be due to a defect in the WT gene itself. In support of this role in
genitourinary development we show that a candidate WT gene is expressed
in specific regions of the developing kidney and in fetal and embryonic
gonads.
10
UI - 8071962
AU - Cowell JK; Jaju R; Kempski H
TI -
Isolation and characterisation of a panel of cosmids which allows
unequivocal identification of chromosome deletions involving the RB1
gene using fluorescence in situ hybridisation.
SO - J Med Genet 1994 Apr;31(4):334-7
AD - ICRF Oncology Group, Institute of Child Health, London, UK.
A series of cosmids covering the majority of the RB1 gene have been
isolated from a flow sorted human chromosome 13 specific library. Using
fluorescence in situ hybridisation these cosmids were all shown to
hybridise to the 13q14 region but not to chromosomes known to carry
subband deletions involving the RB1 gene. This panel of cosmids,
therefore, can be used objectively for identification of RB1 gene
deletions in tumour and normal cells.
11
UI - 7646764
AU - Edington KG; Loughran OP; Berry IJ; Parkinson EK
TI -
Cellular immortality: a late event in the progression of human squamous
cell carcinoma of the head and neck associated with p53 alteration and a
high frequency of allele loss.
SO - Mol Carcinog 1995 Aug;13(4):254-65
AD - Beatson Institute for Cancer Research, CRC Beatson Laboratories,
Glasgow, Scotland.
Many human tumors contain variant cells that, unlike their normal
counterparts, possess indefinite proliferative potential in vitro.
However, little is known of the relevance of these immortal cells to
human carcinomas in vivo. To investigate immortality in a human tumor
system, we established cultures from different stages of head and neck
squamous carcinoma (SCC-HN). All the neoplastic cultures were
transformed because they showed very low cornification in surface or
suspension culture and were partially or completely resistant to
suspension-induced death. Immortal variants were not detected in
premalignant erythroplakia cultures, but their frequency increased with
tumor progression, indicating that immortality is a late event in
carcinogenesis. Some late-stage carcinomas still produced senescent
cultures, but, significantly, all recurrent tumors were immortal.
Immortal but not senescent carcinoma cultures were associated with p53
dysfunction and a high frequency of allele loss, indicative of tumor
suppressor gene inactivation. These results show that there are at least
two classes of human SCC-HN that are phenotypically and genotypically
distinct and that the pathological stage of a given tumor is not
necessarily indicative of the kind of cells it contains.
12
UI - 7475269
AU - Arif M; Tanaka K; Asou H; Ohno R; Kamada N
TI -
Independent clones of trisomy 12 and retinoblastoma gene deletion in
Japanese B cell chronic lymphocytic leukemia, detected by fluorescence
in situ hybridization.
SO - Leukemia 1995 Nov;9(11):1822-7
AD - Department of Cancer Cytogenetics, Hiroshima University, Japan.
Trisomy 12 and a deletion of chromosome 13 are the most common
chromosome abnormalities in patients with B cell chronic lymphocytic
leukemia (B-CLL). We determined the frequencies of these abnormalities
in Japanese B-CLL patients by FISH in interphase nuclei. Specimens from
42 patients were analyzed using both DNA probes specific to the
centromeric region of chromosome 12 and the retinoblastoma (RB) gene.
Among 42 patients, eight had trisomy 12 and 12 had the RB gene deletion.
We found aberrations of trisomy 12 and the RB gene deletion in a totally
different group of patients. This suggested that the trisomy 12 and the
RB gene deletion occur in different clones and the presence of which in
the same patient may be rare. Furthermore, the frequency of trisomy 12
(19%) found in Japanese B-CLL was lower than that in Western countries
(30-35%). On the contrary, the frequency of the RB gene deletion (28.6%)
was almost the same as in European B-CLL (30-35%). These results will be
helpful in understanding the leukemogenesis of B-CLL.
13
UI - 8528059
AU - Zandecki M; Facon T; Preudhomme C; Vanrumbeke M; Vachee A; Quesnel B;
TI -
Lai JL; Cosson A; Fenaux P
The retinoblastoma gene (RB-1) status in multiple myeloma: a report on
35 cases.
SO - Leuk Lymphoma 1995 Aug;18(5-6):497-503
AD - Laboratoire d'Hematologie, A, C.H.U. Lille, France.
We looked for abnormalities of the retinoblastoma (RB-1) gene and of RB
protein expression in 35 patients with multiple myeloma (MM). Mutations
in exons 20 to 24 of the RB-1 gene (exons where mutations predominate in
retinoblastoma and other solid tumors) were analyzed by single stranded
conformation polymorphism (SSCP). RB-1 protein was studied in bone
marrow plasma cells by immunocytochemistry (ABC peroxidase technique)
with a specific monoclonal antibody. Southern blot analysis of RB-1 gene
was also performed in 20 of the patients. Twenty two patients analyzed
had advanced disease (stage III or, in one case, plasma cell leukemia)
and cytogenetic analysis (performed in 31 cases) found monosomy 13 in 9
patients. No rearrangement of the RB-1 gene was found by Southern
analysis. Absent or greatly reduced RB-1 protein level was found in
plasma cells in 4 of the patients (11%), whereas normal levels were seen
in the remaining cases. No point mutation in exons 20 to 24 and their
flanking introns were found in any of the 35 patients. Three of the 4
patients with absent or reduced RB-1 protein expression had advanced MM
(stage III: 2 cases; plasma cell leukemia: 1 case); all 4 patients were
resistant to treatment (as compared to 7 of the 31 patients with normal
RB-1 protein levels); only one of them was subsequently found to have
monosomy 13 (as compared to 9 of the 28 other karyotyped patients). Our
findings suggest that abnormalities of the RB-1 gene and its expression
are rare in MM. Absent or reduced expression of RB-1 protein was not
significantly correlated to monosomy 13 and was not associated with
gross rearrangements of the RB-1 gene by Southern analysis or point
mutations in exons 20 to 24 of the gene. Reduced expression of RB-1
protein may be associated with advanced disease and poor response to
treatment, although larger numbers of patients will be required for more
adequate conclusions.
14
UI - 8866236
AU - Belchis DA; Meece CA; Benko FA; Rogan PK; Williams RA; Gocke CD
TI -
Loss of heterozygosity and microsatellite instability at the
retinoblastoma locus in osteosarcomas.
SO - Diagn Mol Pathol 1996 Sep;5(3):214-9
AD - Department of Pathology, Penn State University College of Medicine,
Hershey, USA.
Studies of osteosarcoma cell lines or frozen tissue have detected loss
of heterozygosity (LOH) at the retinoblastoma (RB) locus by Southern
blot analysis or restriction fragment length polymorphism. Most archived
clinical specimens cannot be analyzed by these techniques. We analyzed
formalin-fixed, paraffin-embedded samples from 19 cases of osteosarcoma
for molecular changes at the RB locus using polymerase chain reaction
amplification of polymorphic short tandem repeat sequences
(microsatellite repeats). Four repeat sequences, two within and two
flanking the RB gene, were analyzed. Fourteen of 18 informative cases
(78%) showed molecular changes at the RB locus. LOH was identified in 13
cases (72%). Unexpectedly, microsatellite instability (MI) was found in
eight cases (44%). All of the cases of MI involved alterations of more
than one repeat unit, and six of eight were associated with LOH. LOH was
identified at three unlinked loci in one case and at a single locus in
another Microsatellite analysis of archival tissue yields prevalence
rates of LOH comparable to those found by other methods and has the
added advantage of showing MI. The ability to use formalin-fixed,
paraffin-embedded tissue extends genetic analysis to routinely processed
surgical material and may permit molecular confirmation of challenging
cases of osteosarcoma.
15
UI - 9209389
AU - Hirai H; Ogawa S; Hangaishi A; Takahashi T; Kurokawa M; Mitani K; Ueda
TI -
R; Yazaki Y
Recent progress in molecular mechanisms of leukemogenesis: the
cyclin-dependent kinase 4-inhibitor gene in human leukemias.
SO - Leukemia 1997 Apr;11 Suppl 3():358-60
AD - Third Department of Internal Medicine, Faculty of Medicine, University
of Tokyo, Japan.
In order to clarify the significance of p16 gene (CDKN2) inactivation
and its disease specificity among hematopoietic tumors, configurations
of the p16 gene as well as those of the adjacent p15 and interferon
alpha (IFN alpha) genes were examined in primary hematopoietic tumors.
Loss of the p16 gene is frequent in and highly specific to lymphoid
tumors among hematopoietic tumors. Gene deletions but not minute
mutations should be the predominant mechanism of p16 gene inactivation
in these types of tumors. The p16 gene is most frequently deleted among
the p16, p15 and IFN alpha genes and thus should be the target of
deletions in this locus. Deletions of the p16 gene were frequently
observed in tumors carrying chromosome 9p abnormalities while a
significant number of cases showed loss of the p16 gene without
chromosome 9p abnormalities. So far inactivation of p53 and Rb tumor
suppressors have also been found in lymphoid tumors. In our study, we
detected homozygous deletions of p16 gene in 20%, loss of Rb protein in
28%, and p53 gene alterations in 8% of lymphoid tumors. Notably, 44% of
lymphoid tumors showed inactivation of at least one of the three tumor
suppressors, suggesting these tumor suppressors are important for
lymphoid tumorigenesis. Inactivations of these tumor suppressors should
independently occur in development of lymphoid tumors.
16
UI - 11519849
AU - Suhardja A; Kovacs K; Rutka J
TI -
Genetic basis of pituitary adenoma invasiveness: a review.
SO - J Neurooncol 2001 May;52(3):195-204
AD - Division of Neurosurgery, University of Toronto, Ontario, Canada.
Compatible with contemporary paradigms of the role of genetic
aberrations in the progression of human tumors, the growth of pituitary
tumors into a state of invasiveness appears to be due to genetic
alterations. Amplification of H-ras and c-myc oncogenes and mutations of
p53, nm23 and Rb genes have been identified disproportionately more in
aggressive tumors and, in the case of Rb gene, in pituitary carcinomas,
providing evidence that amplification of these oncogenes (H-ras and
c-myc) and inactivation of tumor suppressor genes (p53, nm23 and Rb)
seem to be at least one mechanism by which pituitary tumors progress.
The current level of management of invasive pituitary adenomas should
become more comprehensive as the advances in our understanding of
genetic basis of pituitary adenoma invasiveness becomes translated into
development of novel chemotherapy or gene transfer technique.
17
UI - 11414476
AU - Alexander JM
TI -
Tumor suppressor loss in pituitary tumors.
SO - Brain Pathol 2001 Jul;11(3):342-55
AD - Harvard Medical School, Boston, MA, USA. jalexand@caregroup.harvard.edu
The current model of human neoplasia invokes a number of potential
genomic alterations that impact cellular phenotype and proliferative
rates. In the majority of human tumor models, the transformation from
normal cells to neoplastic lesion is a multistep process. This review
offers a specific overview of the involvement of tumor suppressor genes
(TSGs) in the pathogenesis of human pituitary adenomas. TSG genetic
lesions, such as BRCA1 in breast cancer and p53 in Li-Fraumeni Syndrome,
have been identified in both sporadic and heritable human endocrine
tumors. Familial neoplastic syndromes like multiple endocrine neoplasia
type 1 (MEN1) that include pituitary tumor formation as part of a broad
clinical spectrum of disease represent a unique opportunity to
investigate the general mechanisms of tumorigenesis, and well as genes
responsible for sporadic endocrine tumors. Similarly, homologous
recombination knockout mice with selectively ablated candidate TSGs have
also shed light on the molecular mechanisms of pituitary cell
proliferation and tumor suppression. However, despite insights into
pituitary tumorigenesis generated by heritable neoplasia syndromes and
mouse knockout of critical TSGs that display a pituitary tumor
phenotype, the molecular pathogenesis of human pituitary adenomas
remains largely an enigma. Thus, the role of TSGs, if any, in sporadic
pituitary adenoma formation has yet to be determined, despite our
greater understanding of the molecular mechanisms underlying pituitary
cell function and phenotype.
18
UI - 11761929
AU - Nishida N; Fukuda Y
TI -
[Tumor suppressor RB gene and its related molecules in hepatocellular
carcinoma]
SO - Nippon Rinsho 2001 Oct;59 Suppl 6():134-7
AD - Department of Medicine and Clinical Science, Kyoto University Graduate
School of Medicine.
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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