Constitutional mosaic genome-wide uniparental disomy due to diploidisation: an unusual cancer-predisposing mechanism

Beckwith-Wiedemann syndrome (BWS) is one of the commonest syndromes associated to overgrowth. It is caused, in ~10-15% of cases, by a complex mechanism called “paternal uniparental disomy (UPD)”, meaning the inheritance of two paternally derived copies of part of chromosome 11 instead of one copy from each parent. UPD may lead to loss of heterozygosity (LOH; loss of differences between both copies of genetic material), a mechanism observed in some tumours. In this paper we a woman with BWS and tumours with almost complete LOH in all chromosomes, showing a near-complete contribution of the paternal genome.The most plausible explanation for the observed findings is a mechanism called “diploidization” (failure of maternal DNA replication followed by paternal genome duplication). The demonstration of paternal UPD has important implications for medical genetics, counselling and clinical oncology, and emphasises that genomic technologies such as arrays and chips should be used in the diagnosis of patients presenting with dysmorphic features and/or cancer. (By Dr. Pablo Lapunzina, http://jmg.bmj.com/content/early/2010/11/19/jmg.2010.081919.abstract?papetoc )