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  • Andersson, AnnaLund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,MLL-rearrangerad leukemi hos spädbarn,Forskargrupper vid Lunds universitet,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine,The pathogenetic mechanisms behind MLL-rearranged acute leukemia in infancy,Lund University Research Groups (author)

The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias.

  • Article/chapterEnglish2015

Publisher, publication year, extent ...

  • 2015-03-02
  • Springer Science and Business Media LLC,2015

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:f7c9026b-837f-4cd9-a961-79c808db376f
  • https://lup.lub.lu.se/record/5265548URI
  • https://doi.org/10.1038/ng.3230DOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • Infant acute lymphoblastic leukemia (ALL) with MLL rearrangements (MLL-R) represents a distinct leukemia with a poor prognosis. To define its mutational landscape, we performed whole-genome, exome, RNA and targeted DNA sequencing on 65 infants (47 MLL-R and 18 non-MLL-R cases) and 20 older children (MLL-R cases) with leukemia. Our data show that infant MLL-R ALL has one of the lowest frequencies of somatic mutations of any sequenced cancer, with the predominant leukemic clone carrying a mean of 1.3 non-silent mutations. Despite this paucity of mutations, we detected activating mutations in kinase-PI3K-RAS signaling pathway components in 47% of cases. Surprisingly, these mutations were often subclonal and were frequently lost at relapse. In contrast to infant cases, MLL-R leukemia in older children had more somatic mutations (mean of 6.5 mutations/case versus 1.3 mutations/case, P = 7.15 × 10(-5)) and had frequent mutations (45%) in epigenetic regulators, a category of genes that, with the exception of MLL, was rarely mutated in infant MLL-R ALL.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Ma, Jing (author)
  • Wang, Jianmin (author)
  • Chen, Xiang (author)
  • Gedman, Amanda Larson (author)
  • Dang, Jinjun (author)
  • Nakitandwe, Joy (author)
  • Holmfeldt, Linda (author)
  • Parker, Matthew (author)
  • Easton, John (author)
  • Huether, Robert (author)
  • Kriwacki, Richard (author)
  • Rusch, Michael (author)
  • Wu, Gang (author)
  • Li, Yongjin (author)
  • Mulder, Heather (author)
  • Raimondi, Susana (author)
  • Pounds, Stanley (author)
  • Kang, Guolian (author)
  • Shi, Lei (author)
  • Becksfort, Jared (author)
  • Gupta, Pankaj (author)
  • Payne-Turner, Debbie (author)
  • Vadodaria, Bhavin (author)
  • Boggs, Kristy (author)
  • Yergeau, Donald (author)
  • Manne, Jayanthi (author)
  • Song, Guangchun (author)
  • Edmonson, Michael (author)
  • Nagahawatte, Panduka (author)
  • Wei, Lei (author)
  • Cheng, Cheng (author)
  • Pei, Deqing (author)
  • Sutton, Rosemary (author)
  • Venn, Nicola C (author)
  • Chetcuti, Albert (author)
  • Rush, Amanda (author)
  • Catchpoole, Daniel (author)
  • Heldrup, JesperLund University,Lunds universitet,Pediatrik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Paediatrics (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital(Swepub:lu)med-jrh (author)
  • Fioretos, ThoasLund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)kgen-tfi (author)
  • Lu, Charles (author)
  • Ding, Li (author)
  • Pui, Ching-Hon (author)
  • Shurtleff, Sheila (author)
  • Mullighan, Charles G (author)
  • Mardis, Elaine R (author)
  • Wilson, Richard K (author)
  • Gruber, Tanja A (author)
  • Zhang, Jinghui (author)
  • Downing, James R (author)
  • Avdelningen för klinisk genetikInstitutionen för laboratoriemedicin (creator_code:org_t)

Related titles

  • In:Nature Genetics: Springer Science and Business Media LLC47:4, s. 192-3301546-17181061-4036

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