title: Cutaneous T-cell lymphoma-associated lung cancers show chromosomal aberrations differing from primary lung cancer.
abstract: Cutaneous T-cell lymphoma (CTCL) patients have an increased risk of certain secondary cancers, the most common of which are lung cancers, especially small cell lung cancer. To reveal the molecular pathogenesis underlying CTCL-associated lung cancer, we analyzed genomic aberrations in CTCL-associated and reference lung cancer samples. DNA derived from microdissected lung cancer cells of five CTCL-associated lung cancers and five reference lung cancers without CTCL association was analyzed by comparative genomic hybridization (CGH). Fluorescent in situ hybridization (FISH), immunohistochemistry (IHC), and loss of heterozygosity (LOH) analysis were performed for selected genes. In CTCL-associated lung cancer, CGH revealed chromosomal aberrations characterizing both lung cancer and CTCL, but also losses of 1p, and 19, and gains of 4q and 7, hallmarks of CTCL. LOH for the CTCL-associated NAV3 gene was detected in two of the four informative primary lung cancers. FISH revealed increased copy number of the KIT gene in 3/4 of CTCL-associated lung cancers and 1/5 of primary lung cancers. PDGFRA and VEGFR2 copy numbers were also increased. IHC showed moderate KIT expression when the gene copy number was increased. CTCL-associated lung cancer shows chromosomal aberrations different from primary lung cancer, especially amplifications of 4q, a chromosome arm frequently deleted in the latter tumor type. Copy numbers and expression of selected genes in chromosome 4 differed between CTCL-associated and reference lung cancers. These preliminary observations warrant further prospective studies to identify the common underlying factors between CTCL and CTCL-associated lung cancer.
authors.affiliation: Department of Dermatology and Allergology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. sonja.hahtola@helsinki.fi
authors.forename: Sonja
authors.initials: S
authors.lastname: Hahtola
authors.forename: Elke
authors.initials: E
authors.lastname: Burghart
authors.forename: Marjut
authors.initials: M
authors.lastname: Puputti
authors.forename: Leena
authors.initials: L
authors.lastname: Karenko
authors.forename: Wael M
authors.initials: WM
authors.lastname: Abdel-Rahman
authors.forename: Liisa
authors.initials: L
authors.lastname: Väkevä
authors.forename: Leila
authors.initials: L
authors.lastname: Jeskanen
authors.forename: Susanna
authors.initials: S
authors.lastname: Virolainen
authors.forename: Jaakko
authors.initials: J
authors.lastname: Karvonen
authors.forename: Kaisa
authors.initials: K
authors.lastname: Salmenkivi
authors.forename: Vuokko
authors.initials: V
authors.lastname: Kinnula
authors.forename: Heikki
authors.initials: H
authors.lastname: Joensuu
authors.forename: Päivi
authors.initials: P
authors.lastname: Peltomäki
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Klein
authors.forename: Annamari
authors.initials: A
authors.lastname: Ranki
mesh_terms: D000368:Aged; D018288:Carcinoma, Small Cell / Q000235:genetics*; D002869:Chromosome Aberrations; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics*; D016410:Lymphoma, T-Cell, Cutaneous / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization