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The Mutational Landscape in Pediatric Acute Lymphoblastic Leukemia Deciphered by Whole Genome Sequencing
Author(s) -
Lindqvist Carl Mårten,
Nordlund Jessica,
Ekman Diana,
Johansson Anna,
Moghadam Behrooz Torabi,
Raine Amanda,
Övernäs Elin,
Dahlberg Johan,
Wahlberg Per,
Henriksson Niklas,
Abrahamsson Jonas,
Frost BrittMarie,
Grandér Dan,
Heyman Mats,
Larsson Rolf,
Palle Josefine,
Söderhäll Stefan,
Forestier Erik,
Lönnerholm Gudmar,
Syvänen AnnChristine,
Berglund Eva C.
Publication year - 2015
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22719
Subject(s) - biology , genome , genetics , cancer genome sequencing , gene , whole genome sequencing , dna sequencing , transcriptome , computational biology , somatic cell , gene expression
Genomic characterization of pediatric acute lymphoblastic leukemia ( ALL ) has identified distinct patterns of genes and pathways altered in patients with well‐defined genetic aberrations. To extend the spectrum of known somatic variants in ALL , we performed whole genome and transcriptome sequencing of three B‐cell precursor patients, of which one carried the t(12;21) ETV6‐RUNX1 translocation and two lacked a known primary genetic aberration, and one T ‐ ALL patient. We found that each patient had a unique genome, with a combination of well‐known and previously undetected genomic aberrations. By targeted sequencing in 168 patients, we identified KMT2D and KIF1B as novel putative driver genes. We also identified a putative regulatory non‐coding variant that coincided with overexpression of the growth factor MDK . Our results contribute to an increased understanding of the biological mechanisms that lead to ALL and suggest that regulatory variants may be more important for cancer development than recognized to date. The heterogeneity of the genetic aberrations in ALL renders whole genome sequencing particularly well suited for analysis of somatic variants in both research and diagnostic applications.