UI - 9727521
AU - Mohney BG; Robertson DM; Schomberg PJ; Hodge DO
Second nonocular tumors in survivors of heritable retinoblastoma and
prior radiation therapy.
SO - Am J Ophthalmol 1998 Aug;126(2):269-77
AD - Department of Surgery, East Tennessee State University, Johnson City
PURPOSE: The principal objectives of this study were to estimate the
incidence of second tumors among children treated for heritable
retinoblastoma during a 50-year period and to investigate the
relationship between these tumors and previous radiation therapy.
METHODS: The records of all retinoblastoma patients examined at the Mayo
Clinic from 1941 through 1990 were retrospectively reviewed. The
therapeutic modality used to manage the tumor, the occurrence of any
second malignancy, and current follow-up on all patients were evaluated.
RESULTS: Eighty-two (46%) of 180 children with retinoblastoma had
bilateral tumors (76 patients) or unilateral disease and a positive
family history (six patients) and were followed for an average of 21.8
years (range, 1 month to 53 years). The Kaplan-Meier estimates of second
nonocular tumors among the 82 patients with heritable retinoblastoma
were 12% at 10 years, 16% at 25 years, and 30% at 40 years. Although 14
of the 15 patients who developed second malignancies had received
radiation therapy, only four of the malignancies occurred within the
field of irradiation. CONCLUSIONS: The relatively low incidence of
second tumors among long-term survivors of heritable retinoblastoma in
this series of patients occurred predominantly outside the field of
irradiation. The variable incidence of second nonocular malignancies in
previous reports may reflect variations in radiation technique and
UI - 11898356
AU - Babenko OV; Brovkina AF; Zaletaev DV; Kozlova VM; Saakian SV; Nemtsova
[Molecular diagnosis of retinoblastoma. First experience in Russia]
SO - Vestn Oftalmol 2002 Jan-Feb;118(1):28-31
The first experience with molecular diagnosis of retinoblastoma (RB) in
Russia is presented. A protocol based on the use of up-to-date molecular
diagnostic methods helps detect structural and functional abnormalities
in RB1 gene, diagnose RB in disputable cases and at early stages of the
disease. Forty-five families with various forms of RB were examined.
Twenty-three mutations in various sites of RB1 gene were characterized.
Abnormal methylation in the promotor area of RB1 gene was detected in
20% cases and loss of heterozysity by intragene microsatellite markers
was detected in 70% cases. Hence, the causes of RB were detected in 80%
families, which led to early diagnosis in close relatives of patients
and helped evaluate the repeated risk of the tumor in families of
patients with RB.
UI - 12144826
AU - Ho Choi H; Jong HS; Hyun Song S; You Kim T; Kyeong Kim N; Bang YJ
p130 mediates TGF-beta-induced cell-cycle arrest in Rb mutant HT-3
SO - Gynecol Oncol 2002 Aug;86(2):184-9
AD - Cancer Research Center, Seoul National University College of Medicine,
Seoul, Republic of Korea.
OBJECTIVE: The retinoblastoma proteins include Rb and the functionally
and structurally related proteins p107 and p130. It has been reported
that HT-3 cells are sensitive to TGF-beta growth inhibition, despite the
Rb mutation. The purpose of this study was to elucidate the
growth-inhibitory mechanism of TGF-beta in Rb mutant HT-3 cells.
METHODS: Growth inhibition by TGF-beta in cervical carcinoma cell lines
was evaluated by counting cell numbers. Cell-cycle distribution was
determined by staining DNA with propidium iodide (PI) and measured using
a flow cytometer. The level of each protein expression was determined by
Western blot analysis. To evaluate the assembly of cdk2/p21, cdk2/cyclin
E, and E2F-4/p130 complexes by TGF-beta, immunoprecipitation was
performed. RESULTS: TGF-beta inhibited the proliferation of HT-3 cells
expressing mutant Rb protein and efficiently induced cell-cycle arrest
at G(1) phase. p21 protein level was elevated in TGF-beta-treated HT-3
cells, while other G(1) regulatory protein levels were unaltered.
TGF-beta markedly enhanced the binding of p21 with cdk2 but decreased
that of cdk2 with cyclin E and inhibited the phosphorylation of p130 but
did not change Rb and p107 protein status. We also found that E2F-1
protein level was lower in TGF-beta-treated cells and suggest that this
might be the result of enhanced binding between E2F-4 and p130.
CONCLUSIONS: Our results demonstrate that p130, instead of Rb, can
mediate growth inhibition by TGF-beta in Rb mutant HT-3 cells.
UI - 12151885
AU - Ganjavi H; Malkin D
Genetics of childhood cancer.
SO - Clin Orthop 2002 Aug;(401):75-87
AD - Division of Haematology/Oncology, The Hospital for Sick Children,
University of Toronto, Toronto, Ontario, Canada.
In recent years, knowledge of the molecular genetics of childhood
cancers has been increasing at an exponential rate. The study of the
molecular mechanisms of oncogenesis has led to an understanding of the
role that tumor suppressors, oncogenes, and deoxyribonucleic acid (DNA)
repair genes play in development of the disease. Chromosomal
translocations can lead to the disruption of growth regulatory genes or
the formation of growth stimulatory fusion genes in leukemias and solid
tumors. These alterations can occur sporadically or can be inherited,
which often leads to cancer in children or young adults. Often, the
presence of specific genetic alterations can be used to diagnose a
cancer that otherwise would be difficult to verify. Genetic mutations
also can be prognostic indicators and guide the treatment plan of the
UI - 12149641
AU - Betz BL; Strobeck MW; Reisman DN; Knudsen ES; Weissman BE
Re-expression of hSNF5/INI1/BAF47 in pediatric tumor cells leads to G1
arrest associated with induction of p16ink4a and activation of RB.
SO - Oncogene 2002 Aug 8;21(34):5193-203
AD - Department of Pathology and Laboratory Medicine and The Lineberger
Comprehensive Cancer Center, University of North Carolina, Chapel Hill,
North Carolina, NC 27599, USA.
Truncating mutations and homozygous deletions in the hSNF5/INI1/BAF47
subunit of human SWI/SNF complexes occur in most malignant rhabdoid
tumors and some other malignancies. How loss of hSNF5 contributes to
tumorigenesis remains unknown. Because the SWI/SNF subunit BRG1 is
required for RB-mediated cell cycle arrest, we hypothesized that hSNF5
deficiency disrupts RB signaling. Here we demonstrate that unlike BRG1,
hSNF5 deficient cells retain functional RB since ectopic expression of
either p16ink4a or a constitutively active form of RB (PSM-RB) led to
cell cycle arrest. To determine how hSNF5 loss might contribute to
tumorigenesis, we used a retrovirus to introduce hSNF5 into multiple
deficient cell lines. In all cases, re-expression inhibited colony
formation and induced cell cycle arrest characterized by a flattened
morphology. Flow cytometry revealed that these cells accumulated in
G0/G1. Importantly, arrested cells exhibited strong induction of
p16ink4a, hypophosphorylated RB, and down-regulation of cyclin A,
suggesting that hSNF5 signals upstream of RB to induce growth arrest.
Co-expression of SV40 T/t abolished hSNF5-induced G1 arrest and
activation of RB. Likewise, HPV-16 E7 was sufficient to partially
overcome cell cycle arrest. These results suggest that hSNF5 loss is not
equivalent to BRG1/BRM loss in human tumor cell lines. Furthermore,
hSNF5-induced cell cycle arrest of deficient cells is mediated in part
through activation of p16ink4a expression. These findings provide
insight into mechanisms of hSNF5-mediated tumor suppression.
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