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Abramson Cancer CenterNCI CANCERLIT® Search: Retinoblastoma - January 2002
National Cancer Institute®
Last Modified: January 1, 2002
Table of Contents
1
UI - 10646842
AU - Claudio PP; Howard CM; Fu Y; Cinti C; Califano L; Micheli P; Mercer EW;
TI -
Caputi M; Giordano A
Mutations in the retinoblastoma-related gene RB2/p130 in primary
nasopharyngeal carcinoma.
SO - Cancer Res 2000 Jan 1;60(1):8-12
AD - Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson
University, and Sbarro Institute for Cancer Research and Molecular
Medicine, Philadelphia, Pennsylvania 19107, USA.
Nasopharyngeal carcinoma (NPC) is an endemic cancer in southern China
and northern Africa, and its pathogenesis is not yet well defined at the
molecular level. Although the involvement of p53 and of the
retinoblastoma gene (RB/p105) in NPC has been well studied, there is
paucity of mutational data regarding the retinoblastoma-related gene
RB2/p130 in primary tumors and particularly in NPC. We have shown
previously that RB2/p130 could be rearranged in a nasopharyngeal cell
line. In the present study, we screened by single-strand conformation
polymorphism and sequence analysis the retinoblastoma-related gene
RB2/p130 for mutations within exons 19-22. Mutations in the RB2/p130
gene were detected in 3 of 10 primary human NPCs from Northern Africa
(30%). These findings, along with previous data showing that genetic
replacement of RB2/p130 restores a normal growth pathway in the
nasopharyngeal cell line Hone-1, strengthen the hypothesis that genetic
changes of RB2/p130 may be involved in the development and/or
progression of nasopharyngeal cancer and suggest that RB2/p130 could be
considered a tumor suppressor gene and may be a candidate for novel gene
therapeutic approaches for NPC.
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 - 11472099
AU - Hurwitz RL
TI -
Re.:"A Death in the Laboratory".
SO - Mol Ther 2001 Jul;4(1):4
4
UI - 11495315
AU - Ganesh A; Kenue RK; Mitra S
TI -
Retinoblastoma and the 13q deletion syndrome.
SO - J Pediatr Ophthalmol Strabismus 2001 Jul-Aug;38(4):247-50
AD - Department of Ophthalamology, Sultan Qaboos University Hospital, Muscat,
Sultanate of Oman.
5
UI - 11484988
AU - Finol HJ; Marquez A; Navas E; de Navas NR
TI -
Extraocular muscle ultrastructural pathology in the paraneoplastic
phenomenon associated with retinoblastoma.
SO - J Exp Clin Cancer Res 2001 Jun;20(2):281-5
AD - Center for Electron Microscopy, Sciences Faculty, Central University of
Venezuela, Caracas.
Extraocular muscle biopsies were obtained during enucleation because of
advanced intraocular retinoblastoma in four patients admitted to the
Service of Ophthalmology at the Caracas University Hospital. Slight
limitations of ocular movements and strabismus were present in all
cases. The electron microscopical analysis showed muscle fibres with
slight to severe atrophy exhibiting myopathic structures as nemaline,
filamentous and zebra bodies. Fibre necrosis was also observed
characterized by sarcomeric hypercontraction, autophagia, sarcolemmal
disruption, and mitochondrial swelling. Capillary alterations included
endothelial proliferation with intraluminal infoldings and, in some
cases, capillary degeneration and necrosis. A mononuclear cell
infiltration formed by macrophages and scarce mast cells located next to
atrophic fibres and altered capillaries was observed. Additionally,
neutrophils were found around capillaries and in their wall. Cancer
cells invading muscle tissue were not seen. Two different
ethiopathogenic mechanisms for muscle damages seem to be present.
Because of the similarity between the microvascular changes we observed
and those found in the muscle compromise of several autoimmune diseases,
an autoimmune component in the ethiopathogenesis of the observed
capillary alterations is proposed. On the other hand, abnormalities
observed in muscle fibres are very similar to those in neurogenic
atrophy. This study represents the first report on an extraocular muscle
paraneoplastic phenomenon associated with orbital tumours.
6
UI - 11528906
AU - Kubota T
TI -
[Retinoblastoma]
SO - Ryoikibetsu Shokogun Shirizu 2001;(34 Pt 2):579-80
AD - Department of Mental Retardation and Birth Defect Research, National
Institute of Neuroscience, NCNP.
7
UI - 11524739
AU - Yu YS; Kim IJ; Ku JL; Park JG
TI -
Identification of four novel RB1 germline mutations in Korean
retinoblastoma patients.
SO - Hum Mutat 2001 Sep;18(3):252
AD - Department of Ophthalmology, Clinical Research Institute, Seoul National
University Hospital, Seoul, Korea.
To elucidate RB1 germline mutations in Korean retinoblastoma patients,
DNA samples from 14 children with bilateral (including three familial
cases) and 19 children with unilateral retinoblastoma were analyzed. We
found germline mutations in three out of 14 bilateral cases and one out
of 19 unilateral cases. There were no germline mutations in the three
familial cases. PCR-SSCP from each exon showed bandshifts in four
patients which, upon sequencing, were shown to be K616E in exon 19
(c.1846A>G), an AA insertion in exon 7 (c.684-685insAA), R500G in exon
16 (c.1498A>G), and an A insertion in exon 23 (c.2391-2392insA),
respectively. Hum Mutat 18:252, 2001. Copyright 2001 Wiley-Liss, Inc.
8
UI - 11572252
AU - Marta U; Zsuzsanna S; Jozsef B; Zsolt N; Bela S; Gyorgy S
TI -
Rare incidence of three consecutive primary tumors in the maxillofacial
region: retinoblastoma, leiomyosarcoma, and choriocarcinoma: case
report.
SO - J Craniofac Surg 2001 Sep;12(5):464-8
AD - Department of Oral and Maxillofacial Surgery, Semmelweis University,
Budapest, Hungary. marti@szajseb.sote.hu
Multiple primary tumors occur more commonly in the region of the head
and neck than elsewhere in the body. The chance of this is particularly
high in patients treated for retinoblastoma, in part because of a
genetic predisposition, and in part because of the possibility of
irradiation treatment. However, triple tumors occur in only 0.5% of
multiple tumors. A rare case of a triple (metachronous) tumor is
reported: 12 years after the treatment of bilateral retinoblastoma
(enucleation and irradiation), secondary leiomyosarcoma developed in the
maxillofacial region, followed 5 years later by choriocarcinoma. Surgery
was performed on all three types of tumor. As a result, the female
patient (currently 21 years old) is now free of complaints and has
married. It is extremely rare for either leiomyosarcoma or
choriocarcinoma (CHC) to appear in the maxillofacial region. The
long-term, systematic control of such patients is absolutely necessary,
for the multiple tumors tend to develop only after a long latency period
of 10 to 20 years.
9
UI - 11568901
AU - Cohen JG; Dryja TP; Davis KB; Diller LR; Li FP
TI -
RB1 genetic testing as a clinical service: a follow-up study.
SO - Med Pediatr Oncol 2001 Oct;37(4):372-8
AD - Dana Farber Cancer Institute, Smith 201, 44 Binney Street, Boston, MA
02115, USA.
BACKGROUND: Genetic testing for inherited predisposition to diverse
cancers has recently become available as a clinical service. We
conducted a follow-up study of the initial series of US families who
underwent RB1 genetic testing to evaluate long-term effects of the
service. PROCEDURE: We enrolled 52 of 71 eligible families who responded
to a follow-up study questionnaire administered 3-10 years after receipt
of their RB1 results. Each family had one proband with unilateral,
non-familial retinoblastoma, which is associated with a 12% pre-test
probability of hereditary retinoblastoma. RB1 testing identified
germline RB1 mutations in five patients, lowered the carrier probability
to 2% in 21 patients, and did not substantially modify the carrier
probability in the remaining 26. RESULTS: Diverse medical specialists
offered and arranged for RB1 testing, and their recommendation was the
most influential factor in the decision to be tested. Pre-test
counseling was provided by ophthalmologists (30), oncologists (11), and
geneticists and genetic counselors (11). Most respondents, regardless of
test result, were satisfied and perceived gains from their genetic
testing. Based on small numbers, families with reduced likelihood of
hereditary retinoblastoma reported more positive outcomes. Parents of
RB1 carriers were more likely to seek medical services, worry, and
decide against having more children. CONCLUSIONS: This study
demonstrates the feasibility of follow-up studies of families who had
genetic testing. Results from our small series suggest that genetic
information and counseling are important components of RB1 clinical
genetic testing, and long-term adverse effects of testing are uncommon.
Copyright 2001 Wiley-Liss, Inc.
10
UI - 11571558
AU - Genuardi M; Klutz M; Devriendt K; Caruso D; Stirpe M; Lohmann DR
TI -
Multiple lipomas linked to an RB1 gene mutation in a large pedigree with
low penetrance retinoblastoma.
SO - Eur J Hum Genet 2001 Sep;9(9):690-4
AD - Medical Genetics, A. Gemelli School of Medicine, Catholic University,
Rome, Italy.
Hereditary predisposition to lipomas is observed in familial multiple
lipomatosis (OMIM 151900) and benign cervical lipomatosis (OMIM 151800)
and can also be associated with mutations in the MEN1 and PTEN genes
(OMIM 131100 and 153480, respectively). In addition, a recent report
indicates that a few patients with hereditary retinoblastoma also have
lipomas. Here we report on an extended family segregating a splice site
mutation in the RB1 gene. Almost all adult carriers of this mutation had
multiple lipomas while penetrance for retinoblastoma was incomplete. In
an unrelated pedigree, which was reported previously, the identical
mutation was only associated with low-penetrance retinoblastoma but not
lipomas. Our data indicate that lipoma predisposition in hereditary
retinoblastoma is not associated with specific RB1 gene mutations but is
influenced by modifying factors linked to this gene.
11
UI - 11601255
AU - Zhao G; Boysen CD; Brown EF; Hassanein KM; Holmes FF; Holmes GE
TI -
Very long survival in pediatric cancer between 1944 and 1993.
SO - Chin Med J (Engl) 1999 Jul;112(7):615-9
AD - Henan Institute of Medical Sciences, Henan Medical University, Henan
450052, China.
OBJECTIVE: To identify factors associated with very long survival among
all cancer cases diagnosed at age 19 years or younger registered by the
Cancer Data Service at the University of Kansas Medical Center in Kansas
City, Kansas, U.S.A. in the 40-year period between 1944 and 1983, with
follow-up to 1993. METHODS: There were 2720 pediatric patients with 2750
cancers who were studied. Forty-four types of cancer were grouped into
11 diagnostic categories. Diagnosis years spanned four eras: 1944-1953,
1954-1963, 1964-1973, and 1974-1983. Cases were compared using specific
characteristics and were divided into short-term and long-term survivors
with the division generously set at seven years. The proportions of the
long-term survivors were compared by specific characteristics. RESULTS:
Among the diagnostic categories, leukemias were the most common (29.8%),
followed by CNS tumors (15.2%), and Hodgkin's disease (9.0%). Male to
female ratio was 4:3; average age at diagnosis was 8.83 +/- 6.08 years.
Long-term survivors totaled 1148 (41.7%). Prognosis was better in cases
diagnosed in earlier stages and in later eras. Proportion of long-term
survivors increased from 18.7% in era I to 52.6% in era IV. Improvement
of survival was statistically significant in most diagnostic categories.
CONCLUSIONS: This study shows continuing improvement of survival during
four consecutive eras for childhood and adolescent cancer. Early
diagnosis was associated with better survival. Unstaged cases decreased
over time reflecting progress in diagnostic techniques. Many patients
died before seven years after diagnosis. Those who survived more than
seven years had excellent survival. Pediatricians can expect to
participate in the care of these patients long after the original
dianosis and treatment.
12
UI - 11689590
AU - Nishimura S; Sato T; Ueda H; Ueda K
TI -
Acute myeloblastic leukemia as a second malignancy in a patient with
hereditary retinoblastoma.
SO - J Clin Oncol 2001 Nov 1;19(21):4182-3
13
UI - 11702879
AU - Elias WJ; Lopes MB; Golden WL; Jane JA Sr; Gonzalez-Fernandez F
TI -
Trilateral retinoblastoma variant indicative of the relevance of the
retinoblastoma tumor-suppressor pathway to medulloblastomas in humans.
SO - J Neurosurg 2001 Nov;95(5):871-8
AD - Department of Neurological Surgery, University of Virginia Health
Sciences Center, Charlottesville 22908, USA.
Results of recent studies have led investigators to suggest that the
retinoblastoma tumor-suppressor (rb) gene plays an underappreciated role
in the genesis of brain tumors. Such tumors cause significant rates of
mortality in children suffering from hereditary retinoblastoma. It has
been assumed that the pineal gland, which is ontogenetically related to
the retina, accounts for the intracranial origin of these trilateral
neoplasms. To address this issue, the authors describe an unusual
trilateral retinoblastoma variant. The authors provide a detailed
clinicopathological correlation by describing the case of a child with
bilateral retinoblastoma who died of a medulloblastoma. The intraocular
and intracranial neoplasms were characterized by performing detailed
imaging, histopathological, and postmortem studies. Karyotype analysis
and fluorescence in situ hybridization were used to define the
chromosomal defect carried by the patient and members of her family. An
insertion of the q12.3q21.3 segment of chromosome 13 into chromosome 18
at band q23 was identified in members of the patient's family. This
translocation was unbalanced in the proband. The intraocular and
cerebellar neoplasms were found to be separate primary neoplasms.
Furthermore, the pineal gland was normal and the cerebellar neoplasm
arose within the vermis as a medulloblastoma. Finally, the two neoplasms
had different and characteristically identifiable cytolological and
immunohistochemical profiles. The findings of the present study, taken
together with those of recent molecular and transgenic studies, support
the emerging concept that rb inactivation is not restricted to central
nervous system regions of photoreceptor lineage and that inactivation of
this tumor suppressor pathway may be relevant to the determination of
etiological factors leading to medulloblastoma in humans.
14
UI - 11713087
AU - Wilson MW; Rodriguez-Galindo C; Haik BG; Moshfeghi DM; Merchant TE;
TI -
Pratt CB
Multiagent chemotherapy as neoadjuvant treatment for multifocal
intraocular retinoblastoma.
SO - Ophthalmology 2001 Nov;108(11):2106-14; discussion 2114-5
AD - Department of Surgery, St. Jude Children's Research Hospital, Memphis,
Tennessee, USA.
PURPOSE: To evaluate the efficacy of multiagent chemotherapy in the
neoadjuvant treatment of retinoblastoma. DESIGN: Noncomparative,
prospective case series. PARTICIPANTS: Twenty consecutive patients with
multifocal intraocular retinoblastoma (4 unilateral, 16 bilateral [36
eyes]). INTERVENTION: Eight cycles of chemotherapy with carboplatin and
vincristine were administered at 3-week intervals over a 6-month period.
Supplemental therapy was withheld until disease progression was
documented. MAIN OUTCOME MEASURES: Disease progression (defined as tumor
growth, vitreous or subretinal seed progression, and new tumor
formation), delay of external beam radiotherapy, and ocular survival.
RESULTS: Thirty-six eyes were treated. Eighteen eyes had Reese-Ellsworth
group I-III tumors, and 16 eyes had Reese-Ellsworth group IV-V tumors at
diagnosis. Two patients, who had unilateral disease at diagnosis,
subsequently had tumors develop in the contralateral eye. Nineteen of 20
patients (95%) completed eight cycles of chemotherapy without disease
progression. Three eyes of three different patients were successfully
treated with chemotherapy alone. Thirty-three of 36 eyes (92%)
progressed after completion of chemotherapy: 15 of the 18 eyes (83.3%)
with Reese-Ellsworth group I-III and 16 of 16 eyes (100%) with
Reese-Ellsworth group IV-V tumors. Seventeen eyes (52%) had growth of a
tumor, whereas 14 eyes (42%) had progressive vitreous seeding, and 2
eyes (6%) had new tumors develop. Fifteen eyes (42%) required external
beam radiotherapy. Twenty-nine of 36 (80.5%) eyes were salvaged. The
median follow-up after chemotherapy was 19 months (range, 3-42 months).
CONCLUSIONS: Multiagent chemotherapy alone does not ensure a cure for
multifocal intraocular retinoblastoma. Supplemental focal therapy is
needed to control disease progression.
15
UI - 11713089
AU - Shields CL; Shields JA; Cater J; Othmane I; Singh AD; Micaily B
TI -
Plaque radiotherapy for retinoblastoma: long-term tumor control and
treatment complications in 208 tumors.
SO - Ophthalmology 2001 Nov;108(11):2116-21
AD - Oncology Service, Wills Eye Hospital, Thomas Jefferson University,
Philadelphia, Pennsylvania 19107, USA.
OBJECTIVE: To evaluate the clinical factors predictive for tumor
recurrence and treatment complications in a large series of children who
underwent plaque radiotherapy for retinoblastoma. DESIGN: Retrospective,
noncomparative case series. PARTICIPANTS: The participants included 141
children with retinoblastoma who were managed on the Oncology Service at
1999. MAIN OUTCOME MEASURES: Tumor recurrence and treatment
complications. RESULTS: There were 208 tumors managed with plaque
radiotherapy. The mean patient age at plaque treatment was 19 months.
Prior treatment to the retinoblastoma of concern was delivered to 148
tumors (71%) and included various combinations of treatments such as
intravenous chemoreduction, external beam radiotherapy, laser
photocoagulation, thermotherapy, and cryotherapy. For 72 retinoblastomas
(35%), more than one therapeutic method had failed to achieve tumor
control before the use of plaque radiotherapy. Of the 208
retinoblastomas managed with plaque radiotherapy, Kaplan-Meier estimates
of tumor control were 83% at 1 year and 79% at 5 years. Of the 60 tumors
treated only with plaque radiotherapy (primary treatment), recurrence at
1 year was 12%. Of the 148 tumors treated after failure of other methods
(secondary treatment), specific Kaplan-Meier estimates of tumor
recurrence at 1 year was detected in 8% of tumors previously treated
with chemoreduction, 25% of tumors previously treated with external beam
radiotherapy, 34% tumors previously treated with both chemoreduction and
external beam radiotherapy, and 8% of tumors previously treated with
laser photocoagulation, thermotherapy, or cryotherapy (methods other
than chemoreduction and external beam radiotherapy). Using multivariable
analysis, the risks for tumor recurrence included the presence of tumor
seeds in the vitreous, presence of subretinal tumor seeds, and
increasing patient age. Using Kaplan-Meier estimates, radiation
complications at 5 years of follow-up included nonproliferative
retinopathy in 27%, proliferative retinopathy in 15%, maculopathy in
25%, papillopathy in 26%, cataract in 31%, glaucoma in 11%, and scleral
necrosis in 0%. CONCLUSIONS: Plaque radiotherapy for retinoblastoma
provides tumor control in 79% of cases at 5 years of follow-up. It is
particularly useful for those tumors that fail treatment with
chemoreduction, laser photocoagulation, thermotherapy, and cryotherapy.
Tumors in young patients without vitreous or subretinal seeding show the
best long-term control.
16
UI - 11727614
AU - Imhof SM; Moll AC; Schouten-van Meeteren AY
TI -
[Intraocular retinoblastoma: new therapeutic options]
SO - Ned Tijdschr Geneeskd 2001 Nov 10;145(45):2165-70
AD - Afd. Oogheelkunde, VU Medisch Centrum, De Boelelaan 1117, 1081 HV
Amsterdam. s.imhof@vumc.nl
Retinoblastoma is the most frequently occurring primary intraocular
malignant tumour in children (12-15 new patients per year in the
Netherlands). It occurs in one or two eyes. Bilateral retinoblastoma,
which occurs in 40% of the cases, is always hereditary; unilateral
retinoblastoma, which is found in 60% of cases, is hereditary in 10% of
these cases. The presenting symptoms are: leucocoria, strabismus or a
red, painful eye. Early detection of retinoblastoma is important for the
chance of survival, the visual prognosis and preservation of the eye.
The choice of treatment is based on the risk of metastases, the diameter
and the location of the tumour, the age of the patient, the heredity and
the visual prognosis. Nowadays, treatment more often consists of a
combination of techniques. Enucleation is carried out when a large
tumour fills over half of the globe; often this is the only possible
treatment. Small tumours (diameter and thickness < 2 mm) in the centre
of the retina can be treated with laser therapy and those in the
peripheral retina by cryotherapy. Small to medium-sized tumours (< 8 mm
diameter) can be treated with thermochemotherapy: systemic chemotherapy
and laser hyperthermia, if necessary with adjuvant laser therapy or
brachytherapy. Medium-sized tumours (< 8 mm thick) can be treated with
just brachytherapy, sometimes preceded by chemoreduction.
17
UI - 11761559
AU - Wirix M; Parys-Vanginderdeuren R; Casteels I; Uyttebrouck A
TI -
Delayed diagnosis of retinoblastoma.
SO - Bull Soc Belge Ophtalmol 2000;(278):37-41
AD - Department of Ophthalmology, St-Rafael University Hospital,
Capucijnenvoer 33, 3000 Leuven, Belgium.
The aim of our study was to evaluate the age of the patient and the
stage of retinoblastoma at diagnosis and to determine the time delay
between the first symptoms noticed by proxy and the diagnosis of
retinoblastoma. Therefore, thirty-three children between the age of zero
and seven with the diagnosis of uni- or bilateral retinoblastoma were
studied retrospectively. Thirty-one patients were diagnosed with
advanced disease; two patients had small tumors. The mean time delay
between the first clinical symptoms and the diagnosis of retinoblastoma
was 3.2 months (range 2 months to 1 year). In our study most children
with retinoblastoma were diagnosed with advanced disease. In some
patients there was a significant time delay between the first symptoms
and the final diagnosis of retinoblastoma. Better parental and
environmental information regarding symptoms of retinoblastoma could
help to assure earlier detection of tumors.
18
UI - 11709011
AU - Honavar SG; Shields CL; Shields JA; Demirci H; Naduvilath TJ
TI -
Intraocular surgery after treatment of retinoblastoma.
SO - Arch Ophthalmol 2001 Nov;119(11):1613-21
AD - Oncology Service, Wills Eye Hospital, 900 Walnut St, Philadelphia, PA
19107, USA.
OBJECTIVES: To analyze the results of intraocular surgery in patients
treated for retinoblastoma and to assess the ocular and systemic
outcomes. DESIGN: Retrospective noncomparative case series. PATIENTS:
Forty-five consecutive patients who underwent an introcular surgery
after treatment for retinoblastoma. MAIN OUTCOME MEASURES: (1)
Recurrence of retinoblastoma, (2) need for enucleation, and (3) systemic
metastasis. Overall outcome was defined as favorable in the absence of
any of these measures and unfavorable in the presence of 1 or more.
RESULTS: Thirty-four patients (76%) underwent a single procedure of
cataract surgery, a scleral buckling procedure, or pars plana vitrectomy
and 11 (24%) underwent a combination of 2 or more surgical procedures.
In all, 16 patients (36%) achieved final visual acuity better than
20/200. Unfavorable outcomes included recurrence of retinoblastoma in 14
patients (31%), enucleation in 16 (36%), and systemic metastasis in 3
(7%). Five patients (20%) who underwent cataract surgery, 5 (63%) who
underwent a scleral buckling procedure, and 9 (75%) who underwent pars
plana vitrectomy manifested an unfavorable outcome. The median interval
between completion of treatment for retinoblastoma and intraocular
surgery was 26 months in patients with a favorable outcome vs 6 months
in those with an unfavorable outcome. CONCLUSIONS: Intraocular surgery
after treatment for retinoblastoma may be justified in certain
exceptional clinical situations. Cataract surgery is safe and effective
in most cases. However, the need for a scleral buckling procedure and
pars plana vitrectomy may be associated with a higher risk for
recurrence of retinoblastoma, enucleation, and systemic metastasis, and
a cautious approach is warranted.
19
UI - 11709023
AU - Harbour JW
TI -
Molecular basis of low-penetrance retinoblastoma.
SO - Arch Ophthalmol 2001 Nov;119(11):1699-704
AD - Washington University, Campus Box 8069, 660 S Euclid Ave, St Louis, MO
63110, USA. harbour@vision.wustl.edu
Retinoblastoma is a malignant tumor of the retina that occurs primarily
in young children as a result of mutations in the retinoblastoma gene
(RB), the first tumor suppressor gene to be identified. In about 35% to
40% of patients with retinoblastoma, an RB gene mutation is present in
the germline, resulting in hereditary transmission of the disease. Most
families with hereditary retinoblastoma demonstrate autosomal dominant
inheritance with almost complete penetrance and high expressivity.
However, some families display an inheritance pattern characterized by
reduced penetrance and expressivity. Recent advances in our
understanding of the structure and function of the retinoblastoma
protein (pRB) now provide new insights into the molecular basis of this
low-penetrance form of retinoblastoma. Low-penetrance retinoblastoma
mutations either cause a reduction in the amount of normal pRB that is
produced (class 1 mutations) or result in a partially functional mutant
pRB (class 2 mutations).
20
UI - 11753969
AU - Schouten-van Meeteren AY; van der Valk P; van der Linden HC; Moll AC;
TI -
Imhof SM; Huismans DR; Loonen AH; Veerman AJ
Histopathologic features of retinoblastoma and its relation with in
vitro drug resistance measured by means of the MTT assay.
SO - Cancer 2001 Dec 1;92(11):2933-40
AD - Department of Pediatrics, Division Hemato-oncology, Vrije Universiteit
Medical Centre, Amsterdam. n.schouten@vumc.nl
BACKGROUND: Retinoblastoma is frequently treated with chemotherapy to
facilitate intraocular therapy, as well as to diminish or delay
radiotherapy in invasive disease. It is also used more extensively in
patients with dissemination to the central nervous system and/or the
bone marrow. Once the disease has spread, the prognosis is poor.
Radiotherapy is effective in ocular retinoblastoma, but is associated
with facial deformation and a higher chance for second primary tumors in
the irradiation field. These sequelae emphasize the need to determine
more effective chemotherapy schedules and local treatment. The aim of
this study is to investigate the relation between in vitro drug
resistance for ten cytostatic drugs and histopathologic features in
primary retinoblastoma. MATERIALS AND METHODS. Forty-four fresh samples
of primary retinoblastoma were tested for in vitro drug resistance using
the 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyl tetrazolium bromide (MTT)
assay. The histopathologic features for differentiation, invasion and
intra-ocular extension, necrosis, mitosis, and apoptosis were scored.
RESULTS: The differentiation of the tumors revealed 24 poorly
differentiated, 14 intermediately differentiated, and 6 well
differentiated tumors. Tumor infiltration showed 3 minimal and 3 massive
choroideal invasions, as well as 21 prelaminary and 2 postlaminary optic
nerve invasions. The tumor was unifocal in 16 eyes and multifocal in 28
eyes, with extensive retinal involvement in 10 eyes and tumor seeding in
21 eyes. The MTT assay was successful in 82% of the samples after
enzymatic handling of the tumor cells was omitted. Undifferentiated
tumors were more sensitive to carboplatin (p = 0.034) and doxorubicin (p
= 0.025), thiotepa (p = 0.051) and ifosfamide (p = 0.075) in comparison
to differentiated tumors. Type of retinal involvement, invasion,
focality, and seeding did not show a relationship with drug resistance.
Calcified tumors were more resistant to actinomycin D and ifosfamide and
more sensitive to vincristine; conversely, apoptotic tumors were more
sensitive to ifosfamide and more resistant to vincristine (p = 0.027).
Necrotic tumors were more sensitive to actinomycin D (p = 0.004), and
mitotic tumors were more sensitive to idarubicin (p = 0.026). In 90% of
the tumors extreme drug resistance to cytarabin was present.
CONCLUSIONS: In retinoblastoma many histopathologic features are related
to in vitro drug resistance. Undifferentiated tumors are more sensitive
to several cytostatic drugs. Calcification and apoptosis show an inverse
relation with in vitro drug resistance to ifosfamide and vincristine.
Extreme drug resistance to cytarabin is observed; this drug should not
be used in retinoblastoma treatment. Copyright 2001 American Cancer
Society.
21
UI - 11745876
AU - Peylan-Ramu N; Bin-Nun A; Skleir-Levy M; Bibas A; Koplewitz B; Anteby I;
TI -
Pe'er J
Orbital growth retardation in retinoblastoma survivors: work in
progress.
SO - Med Pediatr Oncol 2001 Nov;37(5):465-70
AD - Department of Oncology, Hadassah University Hospital, and Hebrew
University-Hadassah Medical School, Jerusalem, Israel.
ramu@hadassah.org.il
BACKGROUND: Orbital growth retardation, after enucleation and/or
external beam radiation for retinoblastoma (RB), is a serious late
effect. We measured orbital volumes of RB survivors treated at Hadassah
University Hospital, Jerusalem, between 1980-1998. PROCEDURE: Forty-five
orbits of 28 children with RB (17 bilateral, 11 unilateral) were
examined. Thirty-six orbits were irradiated, 19 enucleated, and 10 both
enucleated and irradiated. The orbital volumes were calculated from a
three-dimensional orbital CT reconstruction. The orbits of RB survivors
were compared to age-matched controls. RESULTS: The mean age at
diagnosis was 13 months, mean follow-up time was 56 months. The mean
volume of RB orbits (14.4 cc) was statistically significantly smaller
than control orbits (17.8 cc). There was no difference between the mean
volume of orbits treated with enucleation, irradiation or both. The
orbital volume of children treated before the age of 12 months was
statistically significantly smaller than those treated later. There was
no difference between mean volume of fellow orbits in unilateral RB and
controls. The mean orbital asymmetry index in control children (2.6%)
was statistically significantly smaller than in RB survivors (14%).
CONCLUSIONS: There was a significant orbital growth retardation after
enucleation and/or irradiation for RB. There was no difference between
mean orbital volumes after enucleation, radiation or both. Orbital
growth retardation was most prominent in children treated in the first
year of life. Although small in number, our study suggests that
deferring enucleation and/or irradiation until after the age of 12
months may reduce long-term complications. Copyright 2001 Wiley-Liss,
Inc.
22
UI - 11668642
AU - Jakubowska A; Zajaczek S; Haus O; Limon J; Kostyk E; Krzystolik Z;
TI -
Lubinski J
Novel RB1 gene constitutional mutations found in Polish patients with
familial and/or bilateral retinoblastoma.
SO - Hum Mutat 2001 Nov;18(5):459
AD - Department of Genetics and Pathology, Pomeranian Academy of Medicine,
Szczecin, Poland.
Retinoblastoma is the most common intraocular malignancy in children. It
is estimated that 60 percent of cases are nonhereditary and unilateral,
15% are hereditary and unilateral, and 25 percent are hereditary and
bilateral. Hereditary predisposition for retinoblastoma is caused by
germline mutations in the RB1 gene and is transmitted in an autosomal
dominant manner. Most of the reported mutations are unique to one
family, but there are sites where mutations are recurrent. We have
performed RB1 gene mutation analysis in eight patients with familial
and/or bilateral retinoblastoma by DNA/RNA sequencing. Constitutional
mutations were found in five out of eight patients. Three mutations were
novel: g.IVS7+5G>A, g.156709T>A, and g.IVS21+1G>A (p.G203-E240del,
p.Y659X, and p.I703-E737del). Copyright Wiley-Liss, Inc.
23
UI - 11721186
AU - Dalamon V; Surace E; Borelina D; Ziembar M; Esperante S; Francipane L;
TI -
Davila M; Parma D; Szijan I
Detection of mutations in argentine retinoblastoma patients by
segregation of polymorphisms, exon analysis and cytogenetic test.
SO - Ophthalmic Res 2001 Nov-Dec;33(6):336-9
AD - Genetica y Biologia Molecular, Facultad de Farmacia y Bioquimica,
Universidad de Buenos Aires, Argentina.
The aim of this study was to detect chromosomal and molecular
abnormalities in 16 Argentine families with retinoblastoma (RB).
Chromosomes were analyzed by G-banding, DNA from leukocytes and tumors
was studied by segregation of polymorphisms within RB gene (RB1) and the
DNA from chorionic villus by sequencing. The karyotype of an Rb236
bilateral patient with dismorphic signs revealed a deletion in 13q13-21.
Polymorphism and exon analyses showed a deletion in the 3' end of RB1 in
an Rb72 patient. The mutant RB1 allele, detected by loss of
heterozygosity (LOH) in the tumor, was identified in 14 out of 18
tumors. The analysis of chorionic villus revealed a mutation, a C-to-T
transition in exon 18. Molecular and cytogenetic analyses in families
with RB offer valuable information on how to assess the risk of tumor
development. Copyright 2001 S. Karger AG, Basel
24
UI - 11741800
AU - Desjardins L; Delage M; Lumbroso L; Levy C; Doz F
TI -
[Cured after an intraocular tumor]
SO - Bull Cancer 2001 Nov;88(11):1069-74
AD - Institut Curie, 26, rue d'Ulm, 75005 Paris.
We describe the psychological reactions after diagnosis and treatment of
the malignant intraocular tumors: uveal melanoma and retinoblastoma. The
chapter on uveal melanoma includes general consideration on the
treatment of these tumors, the psychological effects on the patients,
the professional and social problems, the follow-up after treatment and
the results of recent studies on quality of life. For retinoblastoma we
describe the treatments and results with the risk of second cancer, the
follow-up of the patients, the psychological problems for parents and
children and the specificity of the familial cases.
25
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.
26
UI - 2309872
AU - Desai VN; Shields CL; Shields JA; Donoso LA; Wagner RS
TI -
Retinoblastoma associated with holoprosencephaly.
SO - Am J Ophthalmol 1990 Mar 15;109(3):355-6
AD - Oncology Service, Wills Eye Hospital, Philadelphia, PA 19107.
27
UI - 2224792
AU - Greger V; Schirmacher P; Bohl J; Bornemann A; Hurter T; Passarge E;
TI -
Horsthemke B
Possible involvement of the retinoblastoma gene in undifferentiated
sinonasal carcinoma.
SO - Cancer 1990 Nov 1;66(9):1954-9
AD - Institut fur Humangenetik, Universitatsklinikum Essen, Federal Republic
of Germany.
Retinoblastoma tumor formation is initiated by the loss of function of
both alleles of the RB-1 gene on chromosome 13. Patients with the
hereditary form of retinoblastoma carry a germ line mutation at one of
the two homologous gene loci in all cells and have an increased risk for
nonocular tumors (mainly osteosarcoma and other mesenchymal tumors) in
later life. The authors studied a 38-year-old patient with sinonasal
undifferentiated carcinoma (SNUC) who had been treated for bilateral
retinoblastoma by enucleation (left eye) and irradiation (right eye),
respectively. Using molecular probes for the RB-1 gene and other loci on
chromosome 13, the authors detected a deletion at the RB-1 locus in
metastatic SNUC cells that was not present in normal tissue. These
findings indicate that somatic mutations at RB-1 locus may be involved
in the formation or progression of ectodermal tumors.
28
UI - 2096356
AU - Ohnishi Y; Shigeto M; Ishibashi T; Hirata J
TI -
Familial pericentric inversion of chromosome 11 in a child with sporadic
unilateral retinoblastoma.
SO - Ophthalmic Paediatr Genet 1990 Dec;11(4):281-5
AD - Department of Ophthalmology, Faculty of Medicine, Kyushu University,
Fukuoka, Japan.
The authors treated a 12-month-old Japanese boy with sporadic unilateral
retinoblastoma and hereditary chromosomal inversion inv(11)(p11q23).
This chromosomal inversion was also present in the father of the boy.
Cytogenetic analyses of the mother and sister were normal.
Retinoblastoma is associated with constitutional deletion of the long
arm of chromosome 13. The breakpoint in the chromosome 11q23 region is
involved in several malignant hematological diseases, and may be
important in malignant transformation. Therefore, a large number of such
patients with pericentric inversion of chromosome 11 has to be
identified before significance of this chromosomal abnormality can be
determined.
29
UI - 1884549
AU - Araki N; Uchida A; Kimura T; Yoshikawa H; Aoki Y; Ueda T; Takai S; Miki
TI -
T; Ono K
Involvement of the retinoblastoma gene in primary osteosarcomas and
other bone and soft-tissue tumors.
SO - Clin Orthop 1991 Sep;(270):271-7
AD - Department of Orthopaedic Surgery, Osaka University Medical School,
Japan.
The retinoblastoma (Rb) gene, thought by some to be associated with
tumor formation of retinoblastoma as a recessive human oncogene, was
investigated in 57 cases using DNA and RNA from primary osteosarcomas
and other bone and soft-tissue tumors. Eight of 23 osteosarcoma cases
(35%) showed structural alterations of the Rb gene. Three of the eight
demonstrated homozygous deletions, and the remaining five cases showed
heterozygous deletions. Seven out of eight cases represented deletion of
a 7.5-kb HindIII fragment. Northern blot analysis of five cases of
osteosarcoma showed that four demonstrated no detectable Rb gene
transcription, and one case had a truncated 3.5-kb fragment with a faint
4.7-kb band. In the other 34 cases of bone and soft-tissue tumors, two
cases of three malignant fibrous histiocytomas showed an Rb gene
abnormality by Southern blot analysis. These results strongly suggest
that Rb gene alteration is pertinent to the tumorigenesis of most
osteosarcoma cases and some other bone and soft-tissue tumors.
30
UI - 1684533
AU - Hovig E; Lothe R; Farrants G; Brogger A; Fodstad O; Borresen AL
TI -
Chromosome 13 alterations in osteosarcoma cell lines derived from a
patient with previous retinoblastoma.
SO - Cancer Genet Cytogenet 1991 Nov;57(1):31-40
AD - Department of Genetics, Norwegian Radium Hospital, Oslo, Norway.
Various sublines of cells established from an osteosarcoma that
developed in a patient (O.H.) with previous bilateral retinoblastoma
were examined for different restriction fragment-length polymorphisms of
chromosome 13q, as well as for rearrangements of the retinoblastoma gene
using a cDNA probe. The independently established sublines were used to
help separate primary and secondary events taking place in tumorigenesis
of the osteosarcoma of this patient. Information from the present DNA
analysis, taken together with data from cytogenetic and enzymatic
studies on chromosome 13 in the cell lines, revealed both common and
distinct genetic changes on chromosome 13q. The common changes may
indicate the nature of the first and second mutational events in the
development of the osteosarcoma. The first, constitutional cancer
predisposing mutation seemed to be a base mutation or a small
deletion/insertion, and the second event involved a deletion of a larger
part of the long arm of chromosome 13. The distinct genetic changes
included other deletion and duplication events of chromosome 13q. The
existence of multiple sublines with different genetic constitutions
provides improved possibilities for gaining insight into the nature of
the genetic lesions leading to tumor formation, as these may reflect the
clonal variation present in the primary tumor. We also demonstrate the
difficulty of inferring from single tumor cell isolates to properties of
the primary tumor.
31
UI - 1322860
AU - Saw D; Chan JK; Jagirdar J; Greco MA; Lee M
TI -
Sinonasal small cell neoplasm developing after radiation therapy for
retinoblastoma: an immunohistologic, ultrastructural, and cytogenetic
study.
SO - Hum Pathol 1992 Aug;23(8):896-9
AD - Department of Surgical Pathology, New York University Medical Center,
New York.
Patients with retinoblastoma have an increased risk of developing second
primary tumors. Only a few examples of sinonasal small cell neoplasms
developing after radiation therapy for retinoblastoma have been
reported. We report one such case that developed 18 years after
treatment for retinoblastoma. Histologic examination revealed a small,
blue, round cell tumor without rosettes or cytoplasmic glycogen.
Immunohistochemically, the tumor cells were positive for neuron-specific
enolase, synaptophysin, and S-100 protein, but negative for epithelial
and mesenchymal markers, suggesting that
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