Details

Autor(en) / Beteiligte

• Andersson, Anna K
• Ma, Jing
• Wang, Jianmin
• Chen, Xiang
• Gedman, Amanda Larson
• Dang, Jinjun
• Nakitandwe, Joy
• Holmfeldt, Linda
• Parker, Matthew
• Easton, John
• Huether, Robert
• Kriwacki, Richard
• Rusch, Michael
• Wu, Gang
• Li, Yongjin
• Mulder, Heather
• Raimondi, Susana
• Pounds, Stanley
• Kang, Guolian
• Shi, Lei
• Becksfort, Jared
• Gupta, Pankaj
• Payne-Turner, Debbie
• Vadodaria, Bhavin
• Boggs, Kristy
• Yergeau, Donald
• Manne, Jayanthi
• Song, Guangchun
• Edmonson, Michael
• Nagahawatte, Panduka
• Wei, Lei
• Cheng, Cheng
• Pei, Deqing
• Sutton, Rosemary
• Venn, Nicola C
• Chetcuti, Albert
• Rush, Amanda
• Catchpoole, Daniel
• Heldrup, Jesper
• Fioretos, Thoas
• Lu, Charles
• Ding, Li
• Pui, Ching-Hon
• Shurtleff, Sheila
• Mullighan, Charles G
• Mardis, Elaine R
• Wilson, Richard K
• Gruber, Tanja A
• Zhang, Jinghui
• Downing, James R

Titel

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

Ist Teil von

• Nature genetics, 2015-04, Vol.47 (4), p.330-337

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2015

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.