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@ARTICLE{Krieg:291071,
      author       = {S. Krieg$^*$ and T. Rohde and T. Rausch and L. Butthof$^*$
                      and L. Wendler-Link$^*$ and C. Eckert$^*$ and K. Breuhahn
                      and B. Galy$^*$ and J. Korbel and M. Billmann and M.
                      Breinig$^*$ and D. F. Tschaharganeh$^*$},
      title        = {{M}itoferrin2 is a synthetic lethal target for chromosome
                      8p deleted cancers.},
      journal      = {Genome medicine},
      volume       = {16},
      number       = {1},
      issn         = {1756-994X},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DKFZ-2024-01291},
      pages        = {83},
      year         = {2024},
      note         = {#EA:F190#LA:F190#},
      abstract     = {Somatic copy number alterations are a hallmark of cancer
                      that offer unique opportunities for therapeutic
                      exploitation. Here, we focused on the identification of
                      specific vulnerabilities for tumors harboring chromosome 8p
                      deletions.We developed and applied an integrative analysis
                      of The Cancer Genome Atlas (TCGA), the Cancer Dependency Map
                      (DepMap), and the Cancer Cell Line Encyclopedia to identify
                      chromosome 8p-specific vulnerabilities. We employ orthogonal
                      gene targeting strategies, both in vitro and in vivo,
                      including short hairpin RNA-mediated gene knockdown and
                      CRISPR/Cas9-mediated gene knockout to validate
                      vulnerabilities.We identified SLC25A28 (also known as
                      MFRN2), as a specific vulnerability for tumors harboring
                      chromosome 8p deletions. We demonstrate that vulnerability
                      towards MFRN2 loss is dictated by the expression of its
                      paralog, SLC25A37 (also known as MFRN1), which resides on
                      chromosome 8p. In line with their function as mitochondrial
                      iron transporters, MFRN1/2 paralog protein deficiency
                      profoundly impaired mitochondrial respiration, induced
                      global depletion of iron-sulfur cluster proteins, and
                      resulted in DNA-damage and cell death. MFRN2 depletion in
                      MFRN1-deficient tumors led to impaired growth and even tumor
                      eradication in preclinical mouse xenograft experiments,
                      highlighting its therapeutic potential.Our data reveal MFRN2
                      as a therapeutic target of chromosome 8p deleted cancers and
                      nominate MFNR1 as the complimentary biomarker for
                      MFRN2-directed therapies.},
      keywords     = {Humans / Chromosomes, Human, Pair 8: genetics / Animals /
                      Mice / Chromosome Deletion / Neoplasms: genetics / Cell
                      Line, Tumor / Synthetic Lethal Mutations / Mitochondria:
                      metabolism / Mitochondria: genetics / Mitochondrial
                      Proteins: genetics / Mitochondrial Proteins: metabolism /
                      Gene Expression Regulation, Neoplastic / DNA Copy Number
                      Variations / Chromosome 8p deletion (Other) / MFRN1/2
                      paralog buffering (Other) / SCNAs (Other) / Synthetic
                      lethality (Other) / Mitochondrial Proteins (NLM Chemicals)},
      cin          = {F190 / D430},
      ddc          = {610},
      cid          = {I:(DE-He78)F190-20160331 / I:(DE-He78)D430-20160331},
      pnm          = {314 - Immunologie und Krebs (POF4-314)},
      pid          = {G:(DE-HGF)POF4-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38886830},
      doi          = {10.1186/s13073-024-01357-w},
      url          = {https://inrepo02.dkfz.de/record/291071},
}