title: Melanoma addiction to the long non-coding RNA SAMMSON.
abstract: Focal amplifications of chromosome 3p13-3p14 occur in about 10% of melanomas and are associated with a poor prognosis. The melanoma-specific oncogene MITF resides at the epicentre of this amplicon. However, whether other loci present in this amplicon also contribute to melanomagenesis is unknown. Here we show that the recently annotated long non-coding RNA (lncRNA) gene SAMMSON is consistently co-gained with MITF. In addition, SAMMSON is a target of the lineage-specific transcription factor SOX10 and its expression is detectable in more than 90% of human melanomas. Whereas exogenous SAMMSON increases the clonogenic potential in trans, SAMMSON knockdown drastically decreases the viability of melanoma cells irrespective of their transcriptional cell state and BRAF, NRAS or TP53 mutational status. Moreover, SAMMSON targeting sensitizes melanoma to MAPK-targeting therapeutics both in vitro and in patient-derived xenograft models. Mechanistically, SAMMSON interacts with p32, a master regulator of mitochondrial homeostasis and metabolism, to increase its mitochondrial targeting and pro-oncogenic function. Our results indicate that silencing of the lineage addiction oncogene SAMMSON disrupts vital mitochondrial functions in a cancer-cell-specific manner; this silencing is therefore expected to deliver highly effective and tissue-restricted anti-melanoma therapeutic responses.
authors.affiliation: Laboratory For Molecular Cancer Biology, Center for Human Genetics, KULeuven, Herestraat 49, 3000 Leuven, Belgium.|Center for the Biology of Disease, VIB, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Leucci
authors.affiliation: Laboratory For Molecular Cancer Biology, Center for Human Genetics, KULeuven, Herestraat 49, 3000 Leuven, Belgium.|Center for the Biology of Disease, VIB, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: Roberto
authors.initials: R
authors.lastname: Vendramin
authors.affiliation: Center for the Biology of Disease, VIB, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: Marco
authors.initials: M
authors.lastname: Spinazzi
authors.affiliation: Institut de Génétique et de Biologie Moleculaire et Cellulaire (IGBMC), Rue Laurent Fries 1, 67404 Illkirch, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Laurette
authors.affiliation: Center for the Biology of Disease, VIB, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: Mark
authors.initials: M
authors.lastname: Fiers
authors.affiliation: Laboratory of Translational Cell and Tissue Research, Department of Pathology, KULeuven and UZ Leuven, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: Jasper
authors.initials: J
authors.lastname: Wouters
authors.affiliation: Mouse Histopathology Core Facility, Center for the Biology of Disease, VIB-KULeuven, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: Enrico
authors.initials: E
authors.lastname: Radaelli
authors.affiliation: Medical Biotechnology Center, VIB, Albert Baertsoenkaai 3, 9000 Gent, Belgium.|Department of Biochemistry, Gent University, Albert Baertsoenkaai 3, 9000 Gent, Belgium.
authors.forename: Sven
authors.initials: S
authors.lastname: Eyckerman
authors.affiliation: Center for Medical Genetics, Gent University, De Pintelaan 185, 9000 Gent, Belgium.|Cancer Research Institute Gent, Gent University, De Pintelaan 185, 9000 Gent, Belgium.
authors.forename: Carina
authors.initials: C
authors.lastname: Leonelli
authors.affiliation: Center for Medical Genetics, Gent University, De Pintelaan 185, 9000 Gent, Belgium.|Cancer Research Institute Gent, Gent University, De Pintelaan 185, 9000 Gent, Belgium.
authors.forename: Katrien
authors.initials: K
authors.lastname: Vanderheyden
authors.affiliation: Laboratory For Molecular Cancer Biology, Center for Human Genetics, KULeuven, Herestraat 49, 3000 Leuven, Belgium.|Center for the Biology of Disease, VIB, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: Aljosja
authors.initials: A
authors.lastname: Rogiers
authors.affiliation: Gynaecologische Oncologie, KU Leuven, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: Els
authors.initials: E
authors.lastname: Hermans
authors.affiliation: Center for the Biology of Disease, VIB, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Baatsen
authors.affiliation: Laboratory of Computational Biology, Center for Human Genetics, KULeuven, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: Stein
authors.initials: S
authors.lastname: Aerts
authors.affiliation: Gynaecologische Oncologie, KU Leuven, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: Frederic
authors.initials: F
authors.lastname: Amant
authors.affiliation: Department of Applied Mathematics, Computer Science and Statistics, Gent University, De Pintelaan 185, 9000 Gent, Belgium.|Department of Mathematics, KU Leuven, Celestijnenlann 200B, 3001 Leuven, Belgium.
authors.forename: Stefan
authors.initials: S
authors.lastname: Van Aelst
authors.affiliation: Laboratory of Translational Cell and Tissue Research, Department of Pathology, KULeuven and UZ Leuven, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: Joost
authors.initials: J
authors.lastname: van den Oord
authors.affiliation: Center for the Biology of Disease, VIB, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: de Strooper
authors.affiliation: Institut de Génétique et de Biologie Moleculaire et Cellulaire (IGBMC), Rue Laurent Fries 1, 67404 Illkirch, France.
authors.forename: Irwin
authors.initials: I
authors.lastname: Davidson
authors.affiliation: RNA Molecular Biology, Center for Microscopy and Molecular Imaging, Université Libre de Bruxelles (ULB), rue des Professeurs Jeener et Brachet 12, 6041 Charleroi, Belgium.
authors.forename: Denis L J
authors.initials: DL
authors.lastname: Lafontaine
authors.affiliation: Medical Biotechnology Center, VIB, Albert Baertsoenkaai 3, 9000 Gent, Belgium.|Department of Biochemistry, Gent University, Albert Baertsoenkaai 3, 9000 Gent, Belgium.
authors.forename: Kris
authors.initials: K
authors.lastname: Gevaert
authors.affiliation: Center for Medical Genetics, Gent University, De Pintelaan 185, 9000 Gent, Belgium.|Cancer Research Institute Gent, Gent University, De Pintelaan 185, 9000 Gent, Belgium.
authors.forename: Jo
authors.initials: J
authors.lastname: Vandesompele
authors.affiliation: Center for Medical Genetics, Gent University, De Pintelaan 185, 9000 Gent, Belgium.|Cancer Research Institute Gent, Gent University, De Pintelaan 185, 9000 Gent, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Mestdagh
authors.affiliation: Laboratory For Molecular Cancer Biology, Center for Human Genetics, KULeuven, Herestraat 49, 3000 Leuven, Belgium.|Center for the Biology of Disease, VIB, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Marine
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology; D002352:Carrier Proteins; D019070:Cell Lineage; D049109:Cell Proliferation; D002470:Cell Survival; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D002999:Clone Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D005784:Gene Amplification / Q000235:genetics; D055785:Gene Knockdown Techniques; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D024101:Mitochondrial Proteins / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009857:Oncogenes / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000627:therapeutic use; D055757:SOXE Transcription Factors / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: C087299:C1QBP protein, human; D002352:Carrier Proteins; C497234:MITF protein, human; D051739:Microphthalmia-Associated Transcription Factor; D024101:Mitochondrial Proteins; D062085:RNA, Long Noncoding; D055757:SOXE Transcription Factors; D020928:Mitogen-Activated Protein Kinases