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Pathogenesis and consequences of uniparental disomy in cancer.

ABSTRACT: The systematic application of new genome-wide single nucleotide polymorphism arrays has demonstrated that somatically acquired regions of loss of heterozygosity without changes in copy number frequently occur in many types of cancer. Until recently, the ubiquity of this type of chromosomal defect had gone unrecognized because it cannot be detected by routine cytogenetic technologies. Random and recurrent patterns of copy-neutral loss of heterozygosity, also referred to as uniparental disomy, can be found in specific cancer types and probably contribute to clonal outgrowth owing to various mechanisms. In this review we explore the types, topography, genesis, pathophysiological consequences, and clinical implications of uniparental disomy.

SUBMITTER: Makishima H

PROVIDER: S-EPMC3523887 | biostudies-other | 2011 Jun

REPOSITORIES: biostudies-other

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Pathogenesis and consequences of uniparental disomy in cancer.

Makishima Hideki H Maciejewski Jaroslaw P JP

Clinical cancer research : an official journal of the American Association for Cancer Research 20110425 12

The systematic application of new genome-wide single nucleotide polymorphism arrays has demonstrated that somatically acquired regions of loss of heterozygosity without changes in copy number frequently occur in many types of cancer. Until recently, the ubiquity of this type of chromosomal defect had gone unrecognized because it cannot be detected by routine cytogenetic technologies. Random and recurrent patterns of copy-neutral loss of heterozygosity, also referred to as uniparental disomy, can ...[more]

PMID: 21518781

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Uniparental disomy in Robertsonian translocations: strategies for uniparental disomy testing.

Project description:Robertsonian translocations (ROBs) are whole arm rearrangements involving the acrocentric chromosomes 13-15 and 21-22 and carriers are at increased risk for aneuploidy and thus uniparental disomy (UPD). Chromosomes 14 and 15 are imprinted with expression of genes dependent on the parental origin of the chromosome. Correction of a trisomic or monosomic conceptus for chromosomes 14 or 15 would lead to one of the established UPD 14mat/pat or UPD 15 (Prader-Willi/Angelman) syndromes (PWS/AS). In view of this, prenatal UPD testing should be considered for balanced carriers of a ROB, fetuses with a familial or de novo balanced ROB that contains chromosome 14 or 15 or with a normal karyotype when a parent is a carrier of a balanced ROB with a 14 or 15. Individuals with congenital anomalies and an abnormal phenotype and carry a ROB involving the two imprinted chromosomes should also be UPD tested.

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Reciprocal uniparental disomy in yeast.

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Cytogenetic contribution to uniparental disomy (UPD).

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Characterization of Prevalence and Health Consequences of Uniparental Disomy in Four Million Individuals from the General Population.

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Somatic uniparental disomy of Chromosome 16p in hemimegalencephaly.

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Patterns of somatic uniparental disomy identify novel tumor suppressor genes in colorectal cancer.

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CD45-deficient severe combined immunodeficiency caused by uniparental disomy.

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Uniparental disomy and prenatal phenotype: Two case reports and review.

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Uniparental Disomy Causing Myoclonus Dystonia Associated with Russell Silver Syndrome.

Project description: Not available

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Uniparental disomy in a population of 32,067 clinical exome trios.

Project description:PurposeData on the clinical prevalence and spectrum of uniparental disomy (UPD) remain limited. Trio exome sequencing (ES) presents a comprehensive method for detection of UPD alongside sequence and copy-number variant analysis.MethodsWe analyzed 32,067 ES trios referred for diagnostic testing to create a profile of UPD events and their disease associations. ES single-nucleotide polymorphism (SNP) and copy-number data were used to identify both whole-chromosome and segmental UPD and to categorize whole-chromosome results as isodisomy, heterodisomy, or mixed.ResultsNinety-nine whole-chromosome and 13 segmental UPD events were identified. Of these, 29 were associated with an imprinting disorder, and 16 were associated with a positive test result through homozygous sequence variants. Isodisomy was more commonly observed in large chromosomes along with a higher rate of homozygous pathogenic variants, while heterodisomy was more frequent in chromosomes associated with imprinting or trisomy mosaicism (14, 15, 16, 20, 22).ConclusionWhole-chromosome UPD was observed in 0.31% of cases, resulting in a diagnostic finding in 0.14%. Only three UPD-positive cases had a diagnostic finding unrelated to the UPD. Thirteen UPD events were identified in cases with prior normal SNP chromosomal microarray results, demonstrating the additional diagnostic value of UPD detection by trio ES.

| S-EPMC8187148 | biostudies-literature

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