Brandes2023.hemasphere.bib

@ARTICLE{Brandes2023,
  title    = "Optical Genome Mapping Identifies Novel Recurrent Structural
              Alterations in Childhood {ETV6::RUNX1+} and High Hyperdiploid
              Acute Lymphoblastic Leukemia",
  author   = "Brandes, Danielle and Yasin, Layal and Nebral, Karin and Ebler,
              Jana and Schinnerl, Dagmar and Picard, Daniel and Bergmann, Anke
              K and Alam, Jubayer and K{\"o}hrer, Stefan and Haas, Oskar A and
              Attarbaschi, Andishe and Marschall, Tobias and Stanulla, Martin
              and Borkhardt, Arndt and Brozou, Triantafyllia and Fischer, Ute
              and Wagener, Rabea",
  abstract = "The mutational landscape of B-cell precursor acute lymphoblastic
              leukemia (BCP-ALL), the most common pediatric cancer, is not
              fully described partially because commonly applied short-read
              next generation sequencing has a limited ability to identify
              structural variations. By combining comprehensive analysis of
              structural variants (SVs), single-nucleotide variants (SNVs), and
              small insertions-deletions, new subtype-defining and therapeutic
              targets may be detected. We analyzed the landscape of somatic
              alterations in 60 pediatric patients diagnosed with the most
              common BCP-ALL subtypes, ETV6::RUNX1+ and classical hyperdiploid
              (HD), using conventional cytogenetics, single nucleotide
              polymorphism (SNP) array, whole exome sequencing (WES), and the
              novel optical genome mapping (OGM) technique. Ninety-five percent
              of SVs detected by cytogenetics and SNP-array were verified by
              OGM. OGM detected an additional 677 SVs not identified using the
              conventional methods, including (subclonal) IKZF1 deletions.
              Based on OGM, ETV6::RUNX1+ BCP-ALL harbored 2.7 times more SVs
              than HD BCP-ALL, mainly focal deletions. Besides SVs in known
              leukemia development genes (ETV6, PAX5, BTG1, CDKN2A), we
              identified 19 novel recurrently altered regions (in n $\geq$ 3)
              including 9p21.3 (FOCAD/HACD4), 8p11.21 (IKBKB), 1p34.3 (ZMYM1),
              4q24 (MANBA), 8p23.1 (MSRA), and 10p14 (SFMBT2), as well as
              ETV6::RUNX1+ subtype-specific SVs (12p13.1 (GPRC5A), 12q24.21
              (MED13L), 18q11.2 (MIB1), 20q11.22 (NCOA6)). We detected 3 novel
              fusion genes (SFMBT2::DGKD, PDS5B::STAG2, and TDRD5::LPCAT2), for
              which the sequence and expression were validated by long-read and
              whole transcriptome sequencing, respectively. OGM and WES
              identified double hits of SVs and SNVs (ETV6, BTG1, STAG2, MANBA,
              TBL1XR1, NSD2) in the same patient demonstrating the power of the
              combined approach to define the landscape of genomic alterations
              in BCP-ALL.",
  journal  = "Hemasphere",
  volume   =  7,
  number   =  8,
  pages    = "e925",
  month    =  aug,
  year     =  2023,
  language = "en"
}