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The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias.
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- Andersson, Anna (author)
- Lund 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
- Ma, Jing (author)
- Wang, Jianmin (author)
- show more...
- 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)
- 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)
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- (creator_code:org_t)
- 2015-03-02
- 2015
- English.
- In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:4, s. 192-330
- Journal article (peer-reviewed)
Abstract
Subject headings
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- 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
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
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- art (subject category)
- ref (subject category)
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- By the author/editor
- Andersson, Anna
- Ma, Jing
- Wang, Jianmin
- Chen, Xiang
- Gedman, Amanda L ...
- Dang, Jinjun
- show more...
- Nakitandwe, Joy
- Holmfeldt, Linda
- Parker, Matthew
- Easton, John
- Huether, Robert
- Kriwacki, Richar ...
- Rusch, Michael
- Wu, Gang
- Li, Yongjin
- Mulder, Heather
- Raimondi, Susana
- Pounds, Stanley
- Kang, Guolian
- Shi, Lei
- Becksfort, Jared
- Gupta, Pankaj
- Payne-Turner, De ...
- Vadodaria, Bhavi ...
- Boggs, Kristy
- Yergeau, Donald
- Manne, Jayanthi
- Song, Guangchun
- Edmonson, Michae ...
- Nagahawatte, Pan ...
- Wei, Lei
- Cheng, Cheng
- Pei, Deqing
- Sutton, Rosemary
- Venn, Nicola C
- Chetcuti, Albert
- Rush, Amanda
- Catchpoole, Dani ...
- Heldrup, Jesper
- Fioretos, Thoas
- Lu, Charles
- Ding, Li
- Pui, Ching-Hon
- Shurtleff, Sheil ...
- Mullighan, Charl ...
- Mardis, Elaine R
- Wilson, Richard ...
- Gruber, Tanja A
- Zhang, Jinghui
- Downing, James R
- show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
- MEDICAL AND HEAL ...
- and Basic Medicine
- and Medical Genetics
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- Nature Genetics
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- Lund University
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