Retained heterodisomy is associated with high gene expression in hyperhaploid inflammatory leiomyosarcoma.

Summary, in English

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.

• Författare: Karolin Hansén Nord; Kajsa Paulsson; Srinivas Veerla; Johan Wejde; Otte Brosjö; Nils Mandahl; Fredrik Mertens
• Avdelning/ar: BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation; Avdelningen för klinisk genetik; Bröst/lungcancer; Avdelningen för translationell cancerforskning; Bröst- och ovarialcancer; Forskningsgrupp Lungcancer; Bröst/lungcancer
• Publiceringsår: 2012
• Språk: Engelska
• Sidor: 807-812
• Publikation/Tidskrift/Serie: Neoplasia
• Volym: 14
• Issue: 9
• Länkar: http://www.ncbi.nlm.nih.gov/pubmed/23019412?dopt=Abstract
• Dokumenttyp: Artikel i tidskrift
• Förlag: Neoplasia Press
• Ämne: Cancer and Oncology
• Status: Published
• Forskningsgrupp: Breast/lung cancer; Breast and Ovarian Cancer Genomics; Research Group Lung Cancer
• ISBN/ISSN/Övrigt: ISSN: 1522-8002