Overview of rb gene mutations in patients with retinoblastoma: Implications for clinical genetic screening1☆,
Section snippets
Materials and methods
An extensive literature review was undertaken to identify scientific articles published in the English language that report germline (constitutional) mutations in the RB gene in patients with retinoblastoma. Cases were included only if: (1) mutational analysis was performed on DNA obtained from peripheral blood or other nontumor tissue source; (2) data were derived from an original research article; (3) the exact DNA sequence alteration was reported; and (4) intron mutations occurred in
Results
Germline (constitutional) DNA mutations within the RB gene were identified in 192 patients with retinoblastoma reported in 19 scientific articles from Germany (83 patients from Germany and 4 from Argentina),11, 25, 26, 27, 28 France (45 patients),23 the United Kingdom (45 patients),16, 20, 21, 22, 24, 29, 30, 33 Japan (12 patients),18, 19, 32 and the United States (3 patients).17, 31 Eight (4%) of the patients were members of low-penetrance retinoblastoma families.16, 17, 22, 25, 31
Table 1
Discussion
One of the major goals in the treatment of patients with retinoblastoma is to improve the clinical usefulness of genetic testing for patients and their families. Despite the use of modern molecular techniques, there have been several obstacles to achieving this goal:
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The RB gene is very large.
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Mutations occur throughout the gene with no single hotspot.
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The available techniques for directly sequencing the gene are labor intensive and time consuming.
Several groups have used technical shortcuts to
References (39)
- et al.
Predicting the risk of hereditary retinoblastoma
Am J Ophthalmol
(1988) - et al.
The polymerase chain reaction (PCR) in the routine genetic characterization of retinoblastomaa tool for the clinical laboratory
Surv Ophthalmol
(1997) - et al.
Identification of discrete structural domains in the retinoblastoma protein. Amino-terminal domain is required for its oligomerization
J Biol Chem
(1994) - et al.
Integration of cell cycle control with transcriptional regulation by the retinoblastoma protein
Curr Opin Cell Biol
(1993) - et al.
Mortality from second tumors among long-term survivors of retinoblastoma
J Natl Cancer Inst
(1993) Genetics of retinoblastoma
Hum Genet
(1979)- et al.
Unilateral retinoblastomanew intraocular tumours after treatment
Br J Ophthalmol
(1994) - et al.
Cost comparison of molecular versus conventional screening of relatives at risk for retinoblastoma
Am J Hum Genet
(1996) Molecular genetic diagnosis of retinoblastoma
Semin Ophthalmol
(1993)
Frequency of 13q abnormalities among 203 patients with retinoblastoma
J Natl Cancer Inst
Characterization of deletions at the retinoblastoma locus in patients with bilateral retinoblastoma
Am J Med Genet
The spectrum of RB1 germ-line mutations in hereditary retinoblastoma
Am J Hum Genet
Regions of the retinoblastoma gene product required for its interaction with the E2F transcription factor are necessary for E2 promoter repression and pRb-mediated growth suppression
Mol Cell Biol
A single amino acid substitution results in a retinoblastoma protein defective in phosphorylation and oncoprotein binding
Proc Natl Acad Sci U S A
Defective human retinoblastoma protein identified by lack of interaction with the E1A oncoprotein
Cancer Res
Oncogenic point mutations in exon 20 of the RB1 gene in families showing incomplete penetrance and mild expression of the retinoblastoma phenotype
Proc Natl Acad Sci U S A
Oncogenic germ-line mutations in Sp1 and ATF sites in the human retinoblastoma gene
Nature
Mutations in the retinoblastoma gene and their expression in somatic and tumor cells of patients with hereditary retinoblastoma
Hum Mutat
Cited by (113)
Diverse mutational spectrum in the 13q14 chromosomal region in a Brazilian cohort of retinoblastoma
2022, Experimental Eye ResearchCitation Excerpt :Children carrying germline RB1 mutations have 90% risk of developing unilateral or bilateral tumors and other non-ocular neoplasias (DiCiommo et al., 2000). Most constitutive mutations consist of one or a few nucleotide substitutions (Lohmann et al., 1996) but, in some cases, large RB1 and 13q14 deletions as well as copy number variations (CNVs) have been reported (Harbour, 1998; Lohmann, 1999). Identification of the first mutational event in RB patients enables the establishment of prevention strategies, through genetic counseling of carriers and families, for other related malignancies.
Chromosomal microarray analysis of benign mesenchymal tumors with RB1 deletion
2020, Human PathologyCitation Excerpt :See Supplemental Table for a full listing of genetic alterations detected in these cases. RB1, a well-known tumor suppressor gene, has been demonstrated to undergo a myriad of different alterations in disease states [24]. Germ line mutations in RB1, resulting in retinoblastoma, are primarily single-nucleotide variants [24].
Retinoblastoma Genetics: Current Understanding and Future Directions
2020, Advances in Ophthalmology and OptometryCitation Excerpt :Unlike many other cancers, the genome-wide characterization of retinoblastoma epigenomes and transcriptomes is however very limited. Methodologies such as karyotyping and Southern blot were initially used in order to detect loss of RB1 at the chromosomal level [82,83]. The evolution of molecular biology methodologies, such as single-strand conformation polymorphism and denaturing high-performance liquid chromatography, made the detection of point mutations possible.
Pathology of the Conjunctiva, Orbit, Lacrimal Gland, and Intraocular Tumors
2020, Gnepp's Diagnostic Surgical Pathology of the Head and Neck, Third EditionPediatric Oncologic Emergencies
2017, Hematology/Oncology Clinics of North AmericaCitation Excerpt :Practitioners play an important role in identifying patients with no red reflex or strabismus in the newborn nursery or at routine check-ups.10 Approximately 70% of cases of retinoblastoma are unilateral11; in these cases, treatment is predominantly enucleation. When retinoblastoma is bilateral or extends beyond the orbit, radiation, chemotherapy, photocoagulation, and cryotherapy may be required to treat the tumor and preserve residual vision.8
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Supported in part by a Career Development Award from Research to Prevent Blindness, Inc., and in part by NIH grant EY02687.
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The author has no proprietary interest in this study.