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An Integrated Framework for Genome Analysis Reveals Numerous Previously Unrecognizable Structural Variants in Leukemia Patient Samples
Author(s) -
Broach James,
Xu Jie,
Schleicher Emily,
Song Fan,
Pool Christopher,
Hennessy Max,
Sheldon Kathryn,
Annageldiyev Charyguly,
Sharma Arati,
Chang Yuanyuan,
Hastie Alex,
Miller Barbara,
Goldenberg David,
Claxton David,
Moldovan GerogeLucian,
Yue Feng
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.474.1
Subject(s) - biology , gene , genome , genetics , leukemia , copy number variation , somatic cell , computational biology
We have applied a combination of whole genome sequencing and optical genomic mapping to a number of adult and pediatric leukemia samples, which revealed in each of these samples a large number of structural variants not recognizable by current standard genomic analyses. We developed computational methods to determine which of those variants likely arose as somatic mutations. The method identified 97% of the translocations previously reported by karyotype analysis of these samples and revealed an additional fivefold more such somatic rearrangements. The method identified on average tens of previously unrecognizable inversions and duplications and hundreds of previously unrecognizable insertions and deletions. These structural variants affected a number of leukemia associated genes as well as cancer driver genes not previously associated with leukemia and genes not previously associated with cancer. A number of variants only affected intergenic regions but caused cis‐acting alterations in expression of neighboring genes. Analysis of TCGA data indicates that several of the recurrently mutated genes significantly affect survival of AML patients. Our results suggest that current genomic analysis methods fail to identify a majority of structural variants in leukemia samples and this lacunae may hamper diagnostic and prognostic efforts. Support or Funding Information NIH grants R35GM124820, R01HG009906, and U01CA200060; Four Diamonds Fund; George Lafferty Foundation This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .