title: Identification of multiple complex rearrangements associated with deletions in the 6q23-27 region in Sézary syndrome.
abstract: The 6q23-27 region, recurrently deleted in Sézary syndrome (SS), was characterized at the molecular level in 13 SS patients and SS cell line SeAx. Using fine-tiling comparative genomic hybridization, deletions within the 6q23-27 region were detected in half of the samples (six patients and SeAx). All samples with deletions were further analyzed by ligation-mediated PCR. In addition, in one patient sample and in SeAx, paired-end next-generation sequencing was performed on the HiSeq2000 Illumina platform. Using those techniques, 23 rearrangements associated with the deletions were identified. The majority of rearrangements showed enormous complexity and diversity, including eight inversions, three transpositions, and four translocations (with chromosomes 3, 17, 10, and 12). Fifteen genes were disrupted by those rearrangements, the MYB proto-oncogene three times and the interleukin-22 receptor subunit alpha-2 gene (IL22RA2) twice. All three patients with MYB alterations showed low MYB expression, whereas seven of the remaining patients showed overexpression. Most patients overexpressing MYB also presented increased expression of MYC, HSPA8, and BCL2. Five gene fusions were identified, of which two, CCDC28A-IL22RA2 and AIG1-GOSR1, both in SeAx, were in the same orientation and were expressed at the messenger RNA level.
authors.affiliation: Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Iżykowska
authors.affiliation: Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
authors.forename: Mariola
authors.initials: M
authors.lastname: Zawada
authors.affiliation: Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
authors.forename: Karina
authors.initials: K
authors.lastname: Nowicka
authors.affiliation: Clinic for Internal Medicine C, University Greifswald, Greifswald, Germany.
authors.forename: Piotr
authors.initials: P
authors.lastname: Grabarczyk
authors.affiliation: Clinic for Internal Medicine C, University Greifswald, Greifswald, Germany.
authors.forename: Floriane C M
authors.initials: FCM
authors.lastname: Braun
authors.affiliation: Clinic for Internal Medicine C, University Greifswald, Greifswald, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Delin
authors.affiliation: Department of Dermatology and Allergy, Skin Cancer Center, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Möbs
authors.affiliation: Department of Dermatology and Allergy, Skin Cancer Center, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Beyer
authors.affiliation: Department of Dermatology and Allergy, Skin Cancer Center, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Sterry
authors.affiliation: Clinic for Internal Medicine C, University Greifswald, Greifswald, Germany.
authors.forename: Christian A
authors.initials: CA
authors.lastname: Schmidt
authors.affiliation: Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland; Clinic for Internal Medicine C, University Greifswald, Greifswald, Germany. Electronic address: przybylg@man.poznan.pl.
authors.forename: Grzegorz K
authors.initials: GK
authors.lastname: Przybylski
mesh_terms: D000368:Aged; D001483:Base Sequence; D002460:Cell Line; D002896:Chromosomes, Human, Pair 6; D055028:Comparative Genomic Hybridization; D005260:Female; D017353:Gene Deletion; D050939:Gene Fusion / Q000235:genetics; D015321:Gene Rearrangement / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D000090063:Proto-Oncogene Mas; D012751:Sezary Syndrome / Q000235:genetics*