Molecular predictive testing of uveal melanoma
A Peyman MD Gholam, A Meffert MD Stephen, D Conway MD FACS Mandi, Chiasson Trisha in Vitreoretinal Surgical Techniques, 2019
Uveal melanoma is the most common primary cancer of the eye and leads to metastatic death in up to half of affected individuals. Despite advances in treatment of the primary ocular tumor, there has not been a corresponding improvement in survival in uveal melanoma patients. By identifying patients with a high risk primary uveal melanoma at the time of ocular diagnosis, the possibility exists for prophylactic systemic treatment of these patients to delay or prevent the development of overt metastatic disease. Work is also underway to adapt gene expression profile to a non-invasive molecular imaging platform that can be used in the clinic to evaluate all patients with uveal melanocytic tumors without a fine needle biopsy. The first genetic factor that was found to be closely associated with metastasis in uveal melanoma was monosomy 3. Gene expression profiling has also shed new light on the biology of uveal melanoma metastasis.
Genetics
Manoj Ramachandran, Tom Nunn in Basic Orthopaedic Sciences, 2018
A basic knowledge of disease inheritance and relevant genetic musculoskeletal disorders is required by the orthopaedic surgeon. Learn to draw a family pedigree of single-gene inheritance and know the gene mutations of the more common conditions. Chromosomes are structures found within the cell nucleus. Chromosomes are composed of deoxyribonucleic acid (DNA), ribonucleic acid (RNA), polysaccharides and histone and non-histone proteins. Chromosomal abnormalities can involve whole chromosomes or result from structural changes of one or more chromosomes. Monosomy, the loss of one chromosome, occurs less often than an increase in number of chromosomes. In trisomy, the cells have an extra chromosome. The addition of an extra X sex chromosome is seen in Kleinfelter's syndrome (XXY). Mucopolysaccharidoses (MPS) are a group of inherited metabolic disorders caused by deficiency of specific lysosomal enzymes, which results in intracellular accumulation of partially degraded glycoaminoglycans. Duchenne's muscular dystrophy (DMD) is the most common form of muscular dystrophy, and is an X-linked recessive myopathy affecting only males.
Turner Syndrome (TS)
Maggie L Dwiggins in Clinical Protocols in Pediatric and Adolescent Gynecology, 2022
A syndrome characterized by physical findings (such as short stature, signs of gonadal dysgenesis, cardiac defects, and psychosocial impairment) and complete or partial monosomy X with or without mosaicism.
Acquired centromeric heteromorphism of chromosome 7 yields discordant results between fluorescent in situ hybridization and karyotype analysis in a child with severe congenital neutropenia
Published in Pediatric Hematology and Oncology, 2019
Chantal Farra, Susana Raimondi, Miguel Abboud
Monosomy 7 is an indicator of malignant transformation in patients with different subtypes of severe congenital neutropenias (SCNs). We present the case of a 5-year-old male diagnosed with SCN. Standard karyotype and fluorescent in situ hybridization (FISH) analyses for centromere of chromosome 7 (chromosome enumeration probe 7 [CEP7]) in bone marrow samples showed disomy for chromosome 7 and a single copy of CEP7. In all cells examined, karyotype analysis of peripheral PHA-stimulated blood samples revealed disomy for chromosome 7. Our results address the issue of centromeric heteromorphism in cytogenetic analysis. Herein, we report a case where FISH using CEP7 in the bone marrow sample showed the presence of only one signal suggesting monosomy seven due to an acquired heteromorphism, whereas extensive conventional karyotyping showed disomy of chromosome 7.
Retinoschisis and Hyperopia Associated with Partial Monosomy of 6q and Partial Trisomy of 11q
Published in Ophthalmic Genetics, 2014
Nika Bagheri, Reecha S. Bahl, Arun D. Singh, Paul J. Rychwalski
Background: Retinoschisis, or retinal lamellar splitting, can occur in a number of hereditary conditions. The most common cause of congenital or childhood onset retinoschisis is the clinical entity known as juvenile retinoschsis, which is caused by mutations in the X-linked retinoschisis 1 gene. Genes other than X-linked retinoschisis 1 gene have rarely been implicated in association with hereditary retinoschisis. Methods: We describe a 9-year-old male who presented with several phenotypic features associated with partial monosomy of chromosome 6q and partial trisomy of chromosome 11q, including myelomeningocele, mental and growth retardation, seizures, microcephaly, scoliosis, and facial dysmorphisms, as well as novel ocular findings including bilateral retinoschisis and hyperopia. Results: This case report highlights the necessity for a detailed ophthalmic examination of patients with both 6q deletions as well as 11q duplications to ensure accurate and timely diagnosis and treatment of the complications associated with the described ocular conditions.
Chromosome 3 is a valid marker for prognostic testing of biopsy material from uveal melanoma later treated by brachytherapy
Published in Biomarkers, 2019
Claudia Helga Dorothee Le Guin, Klaus Alfred Metz, Nils Lehmann, Stefan Horst Kreis, Norbert Bornfeld, Dietmar Rudolf Lohmann, Michael Zeschnigk
Purpose: Monosomy 3 (M3) in uveal melanoma (UM) obtained after enucleation is significantly associated with metastatic death. With improved biopsy techniques, samples from patients treated with eye-preserving methods have become available. As the choice of treatment depends on tumour size, patients treated with eye-preserving brachytherapy tend to have smaller tumours. It has to be determined if M3 is a valid marker for prognosis of these patients. Methods: Follow-up and clinical data were collected from a total of 451 UM patients: 291 patients were treated by brachytherapy. Tumour tissue was sampled by transretinal biopsy using the 23-gauge Essen biopsy forceps prior to therapy in 114 of them. Chromosome 3 status was determined by microsatellite analysis. Data were compared to those from 160 patients treated by enucleation. Results: Chromosome 3 status correlates significantly with disease-related survival in both patient groups. The proportion of tumours with M3 is lower in the brachytherapy group compared to patients treated with enucleation (25/77 32% and 102/144 71%, respectively). Conclusions: M3 is a valid marker for poor prognosis in uveal melanoma later treated by brachytherapy. The higher proportion of D3 tumours might explain, at least in part, the more favourable prognosis of patients treated by brachytherapy.
Related Knowledge Centers
- Chromosomes
- Diploidy
- Trisomy
- Aneuploidy
- Chromosome
- Turner Syndrome
- Cri-Du-Chat Syndrome