例如:"lncRNA", "apoptosis", "WRKY"

Exome Sequencing of ABCB5 Identifies Recurrent Melanoma Mutations that Result in Increased Proliferative and Invasive Capacities.

J Invest Dermatol. 2019 Sep;139(9):1985-1992.e10. Epub 2019 Mar 21
Géraldine Sana 1 , James P Madigan 2 , Jared J Gartner 3 , Marie Fourrez 1 , Jimmy Lin 4 , Nouar Qutob 5 , Jitendra Narayan 6 , Suneet Shukla 2 , Suresh V Ambudkar 2 , Di Xia 2 , Steven A Rosenberg 7 , Michael M Gottesman 8 , Yardena Samuels 9 , Jean-Pierre Gillet 10
Géraldine Sana 1 , James P Madigan 2 , Jared J Gartner 3 , Marie Fourrez 1 , Jimmy Lin 4 , Nouar Qutob 5 , Jitendra Narayan 6 , Suneet Shukla 2 , Suresh V Ambudkar 2 , Di Xia 2 , Steven A Rosenberg 7 , Michael M Gottesman 8 , Yardena Samuels 9 , Jean-Pierre Gillet 10
+ et al

[No authors listed]

Author information
  • 1 Laboratory of Molecular Cancer Biology, Molecular Physiology Research Unit (URPHYM), Namur Research Institute for Life Sciences, Faculty of Medicine, Department of Biomedical Sciences, University of Namur, Namur, Belgium.
  • 2 Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
  • 3 Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
  • 4 Washington University School of Medicine, Genome Technology Access Center, Genomics and Pathology Services, St. Louis, Missouri, USA.
  • 5 Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
  • 6 Laboratory of Evolutionary Genetics and Ecology (LEGE), Faculty of Sciences, Department of Biology, University of Namur, Namur, Belgium.
  • 7 Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
  • 8 Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Electronic address: mgottesman@nih.gov.
  • 9 Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
  • 10 Laboratory of Molecular Cancer Biology, Molecular Physiology Research Unit (URPHYM), Namur Research Institute for Life Sciences, Faculty of Medicine, Department of Biomedical Sciences, University of Namur, Namur, Belgium. Electronic address: jean-pierre.gillet@unamur.be.

摘要


ABCB5 is an ABC transporter that was shown to confer low-level multidrug resistance in cancer. In this study, we show that ABCB5 was mutated in 13.75% of the 640 melanoma samples analyzed. Besides nonsense mutations, two mutation hotspots were found in the ABCB5 protein, in the drug-binding pocket and the nucleotide-binding domains. Four mutations, which are representative of the mutation pattern, were selected. ATPase assays showed that these mutations resulted in a decrease in basal ATP hydrolysis by ABCB5. To select informative melanoma cell lines, mutational profiles of the clinical samples were further analyzed. This study showed mutations in the tumor suppressor CDKN2A gene and the NRAS oncogene in 62.5% and 75%, respectively of the samples that had mutations in the ABCB5 gene. No mutation was found in the tumor suppressor PTEN gene, whereas the activating V600E mutation in the BRAF oncogene was found in 25% of the samples with a mutated ABCB5 gene. Studies in four melanoma cell lines with various genetic backgrounds showed an increase in the proliferation and migration capacity of mutant ABCB5-expressing cells, suggesting that ABCB5 plays a role in the development of melanoma as a tumor suppressor gene.