Chromosome 11 uniparental isodisomy predisposing to embryonal neoplasms

Molecular karyotyping of human hepatocellular carcinoma using single-nucleotide polymorphism arrays

“…Uniparental disomy or UPT are exceptional derivations of a pair of offspring chromosomes from one parent only (Engel, 1980) and cause an increased risk of recessive disorders, such as Wiedemann-Beckwith (Henry et al, 1991), Prader-Willi (Nicholls et al, 1989) and Angelman syndromes (Malcolm et al, 1991) owing to reduction to homozygosity (Engel, 1993). Furthermore, UPD regions have been shown to contain genes responsible for carcinogenesis, which have been implicated in Wilms' tumor (Grundy et al, 1994), leukemia (Raghavan et al, 2005) and breast cancer (Murthy et al, 2002), but have never been described in HCC. Our data showed that UPD is frequently observed on chromosome 6q, 10q and 13q, where LOH is observed repeatedly and contains suppressor genes, such as PTEN, DMBT1, BRCA2, RB and DLC2.…”

“…Allelic changes, including hemizygous deletion with a gain of the opposite allele, so-called uniparental disomy (UPD) or trisomy (UPT), are important in elucidating the molecular mechanisms of cancer (Engel, 1980). For example, accurate determination of the copy number of each allele separately in the UPD region, which may contain a region of methylation or null mutation of tumor suppressor genes, may allow the mechanism of carcinogenesis to be determined more clearly and comprehensively (Grundy et al, 1994;Murthy et al, 2002;Raghavan et al, 2005). In addition, accurate measurement of changes in copy number using high-resolution methods will help in the detection of heterogeneous populations among cancer cells (Benetkiewicz et al, 2005;Buckley et al, 2005).…”

Beckwith–Wiedemann syndrome

“…This spectrum includes children with features of BWS who do not fulfill clinical diagnostic criteria, as well as children with isolated hemihyperplasia (IH) [26][27][28][29][30] or isolated Wilms tumor. 30 There are no absolute requisites for the clinical diagnosis of BWS.…”

“…Of note, epigenetic alterations in 11p15 including somatic mosaicism for paternal UPD for 11p15 and methylation alterations at IC1 or IC2 have been reported in IH with or without embryonal tumors. [26][27][28][29] MOLECULAR BASIS OF BWS Most mammalian autosomal genes are expressed from both the maternally and paternally inherited copies of a chromosome pair. However, some genes undergo genomic imprinting and are expressed monoallelically in a parent-of-origin-specific manner.…”

Mosaic segmental uniparental isodisomy and progressive clonal selection: a common mechanism of late onset -thalassemia major

“…Beta-thalassemia intermedia patients with a mitotic LoH in the hematopoietic lineage due to a deletion containing the unaffected β-globin gene has been reported by Badens et al and Galanello et al 8,9 Somatic deletions giving rise to loss of heterozygosity have been discovered and studied in the context of carcinogenesis. 10,11 However, as MLPA and Illumina SNP array analysis showed no deletion involving the β-globin gene or neighboring region in the DNA isolated from blood of any of these independent patients, another molecular cause was expected. A previously reported case of late-onset β-thalassemia by Chang et al, 12 and a sickle cell disease case reported by Swensen et al, 13 involve LoH due to segmental isodisomy of chromosome 11p.…”