title: Copy number alterations at polymorphic loci may be acquired somatically in patients with myelodysplastic syndromes.
abstract: Loss of genomic integrity is thought to be one of the underlying causes of myelodysplastic syndromes (MDS). However, it is unclear whether changes in copy number at loci that are common sites of copy number polymorphisms play a pathogenic role. Here we show that copy number changes in the MDS clone that occur at polymorphic loci are frequently somatic alterations rather than constitutional variants, and the extent of copy number changes at polymorphic loci is increased in CD34(+) cells of MDS patients compared to age-matched controls. This study suggests a potential pathophysiological role for copy number alterations at polymorphic loci in patients with MDS, and highlights the need for somatic control tissues for each patient studied in high-resolution genome-wide investigations.
authors.affiliation: Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, Canada.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Starczynowski
authors.forename: Suzanne
authors.initials: S
authors.lastname: Vercauteren
authors.forename: Sandy
authors.initials: S
authors.lastname: Sung
authors.forename: Angela
authors.initials: A
authors.lastname: Brooks-Wilson
authors.forename: Wan L
authors.initials: WL
authors.lastname: Lam
authors.forename: Aly
authors.initials: A
authors.lastname: Karsan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000097:blood; D017252:CD3 Complex / Q000097:blood; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D005260:Female; D018628:Gene Dosage; D056426:Genetic Loci / Q000235:genetics*; D006801:Humans; D008297:Male; D008390:Markov Chains; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic; D011379:Prognosis
chemical_list: D018952:Antigens, CD34; D017252:CD3 Complex