Acute_Lymphoblastic_Leukemia_Exome_sequencing_2_

Agilent whole exome hybridisation capture will be performed on genomic DNA derived from 50 Acute Lymphoblastic Leukemia samples and matched normal DNA from the same patients. Three lanes of Illumina GA sequencing will be performed on the resulting 100 exome libraries and mapped build 37 of the human reference genome to facilitate the identification of novel cancer genes. In addition, 500bp, NO_PCR total genomic libraries will be prepared from the same samples and five lanes of Illumina GA sequencing will be analysed to characterise genome wide, somatically acquired structural variation.

Type: Cancer Genomics
Archiver: European Genome-Phenome Archive (EGA)

2 Datasets 3 Publications

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001000104	Acute Lymphoblastic Leukemia Exome sequencing 2	Illumina Genome Analyzer II	97
EGAD00001000636	The ETV6-RUNX1 fusion gene, found in 25% of childhood acute lymphoblastic leukemia (ALL), is acquired in utero but requires additional somatic mutations for overt leukemia. We used exome and low-coverage whole-genome sequencing to characterize the critical secondary events associated with leukemic transformation. RAG-mediated deletions emerge as the dominant mutational process, accounting for at least 43% of genomic rearrangements and characterized by the presence of recombination signal sequence motifs near the breakpoints; incorporation of non-templated sequence at the junction and a ten-fold enrichment at promoters and enhancers of genes actively transcribed in early B-lineage development. Single-cell tracking shows that this mechanism is not restricted to one founder cell but is rather active throughout leukemic evolution. Integration of point mutation and rearrangement data identifies recurrent inactivation of ATF7IP and MGA as two new tumor suppressor genes.Thus, a remarkably parsimonious mutational process transforms ETV6-RUNX1 lymphoblasts, striking promoters and enhancers of the genes that normally control B-cell differentiation.	Illumina Genome Analyzer II	117

Publications	Citations
Single-cell mutational profiling and clonal phylogeny in cancer. Potter NE, Ermini L, Papaemmanuil E, Cazzaniga G, Vijayaraghavan G, Titley I, Ford A, Campbell P, Kearney L, Greaves M. Genome Res 23: 2013 2115-2125	81
RAG-mediated recombination is the predominant driver of oncogenic rearrangement in ETV6-RUNX1 acute lymphoblastic leukemia. Papaemmanuil E, Rapado I, Li Y, Potter NE, Wedge DC, Tubio J, Alexandrov LB, Van Loo P, Cooke SL, Marshall J, Martincorena I, Hinton J, Gundem G, van Delft FW, Nik-Zainal S, Jones DR, Ramakrishna M, Titley I, Stebbings L, Leroy C, Menzies A, Gamble J, Robinson B, Mudie L, Raine K, O'Meara S, Teague JW, Butler AP, Cazzaniga G, Biondi A, Zuna J, Kempski H, Muschen M, Ford AM, Stratton MR, Greaves M, Campbell PJ. Nat Genet 46: 2014 116-125	231
Chemotherapy induces canalization of cell state in childhood B-cell precursor acute lymphoblastic leukemia. Turati VA, Guerra-Assunção JA, Potter NE, Gupta R, Ecker S, Daneviciute A, Tarabichi M, Webster AP, Ding C, May G, James C, Brown J, Conde L, Russell LJ, Ancliff P, Inglott S, Cazzaniga G, Biondi A, Hall GW, Lynch M, Hubank M, Macaulay I, Beck S, Van Loo P, Jacobsen SE, Greaves M, Herrero J, Enver T. Nat Cancer 2: 2021 835-852	17