title: Molecular markers associated with clinical response to bexarotene therapy in cutaneous T-cell lymphoma.
abstract: Bexarotene (Targretin(®)), was registered for the treatment of cutaneous T-cell lymphoma (CTCL) in 2002, and has been reported to induce a 45% overall response. Responses are mostly partial or generate a stable, skin-restricted disease. This study explored the usefulness of a novel cancer-associated gene, NAV3 and corresponding chromosome 12 copy numbers as possible biomarkers to monitor the therapeutic response to bexarotene in 21 Finnish patients with CTCL. Six patients (29%) reached complete remission (CR) and 3 of these remained in CR for more than 24 months, 12 (57%) reached a partial response (PR, with one stable disease) and 3 were non-responders. Low-level NAV3 deletions were detected using a fluorescence in-situ hybridization (FISH) assay in the lesions of 5 patients, 4 of whom were non-responders or progressed after short PR. This occurrence of NAV3 deletions was statistically significant compared with non-progressors (p = 0.011, Fisher's exact test). Chromosome 12 tetraploidy was found in the lesions of two of the 3 patients with CR who remained in remission. While such tetraploidy is a feature of proliferating normal T cells, this observation may reflect a favourable anti-tumour immune response among the skin-infiltrating lymphocytes.
authors.affiliation: Department of Dermatology and Allergic Diseases, University of Helsinki, Finland. annamari.ranki@hus.fi
authors.forename: Annamari
authors.initials: A
authors.lastname: Ranki
authors.forename: Liisa
authors.initials: L
authors.lastname: Väkevä
authors.forename: Laura
authors.initials: L
authors.lastname: Sipilä
authors.forename: Kai
authors.initials: K
authors.lastname: Krohn
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000077610:Bexarotene; D014408:Biomarkers, Tumor / Q000235:genetics*; D002478:Cells, Cultured; D002881:Chromosomes, Human, Pair 12; D005387:Finland; D017353:Gene Deletion; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D018579:Patient Selection; D010597:Pharmacogenetics; D057285:Precision Medicine; D012074:Remission Induction; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D013764:Tetrahydronaphthalenes / Q000627:therapeutic use*; D057891:Tetraploidy; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D008565:Membrane Proteins; C464453:NAV3 protein, human; D009419:Nerve Tissue Proteins; D013764:Tetrahydronaphthalenes; D000077610:Bexarotene