Mechanisms of uniparental disomy in myeloma. (A) In a normal cell (i) both parental alleles are present. During mitosis incomplete segregation of chromosomes can occur (ii) resulting in either monosomic or trisomic cells for a particular chromosome. UPD of a whole chromosome can then occur (iii) through mitotic nondisjunction, where the remaining chromosome is duplicated in the monosomic cell, or where the outnumbered allele is deleted in the trisomic cell. Alternatively, during mitosis (iv) recombination between chromatids can occur resulting in UPD of an arm of a chromosome (v) or part of an arm to the telomere (vi). If multiple recombination events occur during mitosis then interstitial regions of UPD can occur (vii-viii). (B) UPD in a myeloma sample occurring through mitotic nondisjunction on chromosome 12. (C) Uniparental trisomy occurring in myeloma by mitotic recombination and gain of chromosome 1q. (D) UPD occurring in myeloma by deletion of the telomere of chromosome 2. Regions of LOH are shown in blue, with heterozygous regions in yellow. Copy number is shown by both the red bar and the gray panel, where the blue line represents the copy number of the sample and the red line a copy number of 2 (with the edges of the gray panel indicating copy numbers of 1 [left] and 3 [right]). The sample is shown pictorially alongside.