title: Retained heterodisomy is associated with high gene expression in hyperhaploid inflammatory leiomyosarcoma.
abstract: Inflammatory leiomyosarcoma (ILMS) is a soft tissue tumor that morphologically resembles conventional leiomyosarcoma (LMS) admixed with a prominent inflammatory infiltrate. Genetic data on ILMS are still limited but have suggested that this entity is characterized by hyperhaploidy (24-34 chromosomes). This low chromosome number is otherwise uncommon in neoplasia and has been found only in 0.2% to 0.3% of cytogenetically investigated tumors. Here, three ILMS were investigated using cytogenetic, single-nucleotide polymorphism (SNP) array, and global gene expression analyses. All cases displayed a hyperhaploid origin. Combined with previously reported cases, hyperhaploidy has been found in six of seven cytogenetically investigated ILMS. The copy number distribution of individual chromosomes is clearly nonrandom; the hyperhaploid clones of all six cases displayed disomy for chromosomes 5 and 20, and two copies of chromosomes 18, 21, and 22 were also common. All chromosomes identified as disomic showed a biparental origin by SNP array analysis; whether this is of pathogenetic importance is not known. Compared with conventional LMS, ILMS had a distinct gene expression signature. Furthermore, the number of chromosome copies correlated well with gene expression levels; disomic chromosomes showed higher gene expression levels than monosomic chromosomes, a finding that has not previously been reported for hyperhaploid tumors. Taken together, our findings suggest that disomy for some chromosomes, notably 5 and 20, as well as distorted gene expression achieved through massive loss of other chromosomes are essential features of ILMS.
authors.affiliation: Department of Clinical Genetics, University and Regional Laboratories, Skåne University Hospital, Lund University, Lund, Sweden. Karolin.Hansen_Nord@med.lu.se
authors.forename: Karolin H
authors.initials: KH
authors.lastname: Nord
authors.forename: Kajsa
authors.initials: K
authors.lastname: Paulsson
authors.forename: Srinivas
authors.initials: S
authors.lastname: Veerla
authors.forename: Johan
authors.initials: J
authors.lastname: Wejde
authors.forename: Otte
authors.initials: O
authors.lastname: Brosjö
authors.forename: Nils
authors.initials: N
authors.lastname: Mandahl
authors.forename: Fredrik
authors.initials: F
authors.lastname: Mertens
mesh_terms: D000328:Adult; D002890:Chromosomes, Human, Pair 20; D002892:Chromosomes, Human, Pair 22; D002895:Chromosomes, Human, Pair 5; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007249:Inflammation / Q000473:pathology; D007890:Leiomyosarcoma / Q000235:genetics* / Q000473:pathology; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D024182:Uniparental Disomy; D055815:Young Adult