National Cancer Institute®
Last Modified: January 1, 2002
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.
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.
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.
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.
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.
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.
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. firstname.lastname@example.org
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.
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.
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.
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.
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
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.
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.
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.
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. email@example.com
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.
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.
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.
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. firstname.lastname@example.org
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).
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. email@example.com
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.
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. firstname.lastname@example.org
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.
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.
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
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.
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.
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.
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.
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.
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.
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.
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