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Author (up) Bateman, C.M.; Alpar, D.; Ford, A.M.; Colman, S.M.; Wren, D.; Morgan, M.; Kearney, L.; Greaves, M. url  doi
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  Title Evolutionary trajectories of hyperdiploid ALL in monozygotic twins Type Journal Article
  Year 2015 Publication Leukemia Abbreviated Journal Leukemia  
  Volume 29 Issue 1 Pages 58-65  
  Keywords  
  Abstract Identical twins have provided unique insights on timing or sequence of genetic events in acute lymphoblastic leukaemia (ALL). To date, this has mainly focused on ALL with MLL or ETV6-RUNX1 fusions, with hyperdiploid ALL remaining less well characterised. We examined three pairs of monozygotic twins, two concordant and one discordant for hyperdiploid ALL, for single-nucleotide polymorphism (SNP)-defined copy number alterations (CNAs), IGH/L plus TCR gene rearrangements and mutations in NRAS, KRAS, FLT3 and PTPN11 genes. We performed whole exome sequencing in one concordant twin pair. Potential 'driver' CNAs were low, 0-3 per case, and all were different within a pair. One patient had an NRAS mutation that was lacking from leukaemic cells of the twin sibling. By exome sequencing, there were 12 nonsynonymous mutations found in one twin and 5 in the other, one of which in SCL44A2 was shared or identical. Concordant pairs had some identical IGH/L and TCR rearrangements. In the twin pair with discordant hyperdiploid ALL, the healthy co-twin had persistent low level hyperdiploid CD19+ cells that lacked a CNA present in the ALL cells of her sibling. From these data, we propose that hyperdiploid ALL arises in a pre-B cell in utero and mutational changes necessary for clinical ALL accumulate subclonally and postnatally.  
  Address Centre for Evolution and Cancer, The Institute of Cancer Research, Sutton, UK  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0887-6924 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:24897505 Approved no  
  Call Number CBM.UAM @ ccobaleda @ Serial 544  
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