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Title: | Acquisition of genome-wide copy number alterations in monozygotic twins with acute lymphoblastic leukaemia |
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List of authors: | Bateman, CM; Colman, SM; Chaplin, T; Young, BD; Eden, TO; Bhakta, M; Gratias, EJ; van Wering, ER; Cazzaniga, G; Harrison, CJ; Hain, R; Ancliff, P; Ford, A.M; Kearney, L; & Greaves, M |
Reference: | Blood. 2010 - Online 8th Jan 2010 |
Year of Publication: | 2010 |
Abstract: | Chimaeric fusion genes are highly prevalent in childhood acute lymphoblastic leukaemia (ALL) and are mostly pre-natal, early genetic events in the evolutionary trajectory of this cancer. ETV6-RUNX1-positive ALL also has multiple (~six per case) copy number alterations (CNA) as revealed by genome-wide SNP arrays. Recurrent CNA are probably ‘driver’ events contributing critically to clonal diversification and selection but, at diagnosis, their developmental timing is ‘buried’ in the leukaemia’s covert natural history. This conundrum can be resolved with twin pairs. We identified and compared CNA in five pairs of monozygotic twins with concordant ETV6-RUNX1-positive ALL and one pair discordant for ETV6-RUNX1 positive ALL. We compared, within each pair, CNA classified as potential ‘driver’ or ‘passenger’ mutations based upon recurrency and, where known, gene function. An average of 5.1 (range 3-11) CNAs (excluding immunoglobulin/T-cell receptor alterations) were identified per case. All ‘driver’ CNA (total 32) were distinct within each of the five twin pairs with concordant ALL. ‘Driver’ CNA in another twin with ALL were all absent in the shared ETV6-RUNX1-positive pre-leukaemic clone of her healthy co-twin. These data place all ‘driver’ CNA secondary to the pre-natal gene fusion event and most probably post-natal in the sequential, molecular pathogenesis of ALL. |
PMID: | |
Supplementary Data: |
SNP Genotype Data The SNP Genotype Data for the patients detailed in Table 2 and in Supplementary Table 4S are listed below. The following key deciphers the file names. Key: LEUK= DNA from Leukaemic bone marrow at presentation of ALL REM = DNA from Remission blood, as a germline control NSP = Affymetrix 250K Nsp1 array STY = Affymetrix 250K Sty1 array
Twin1a_LEUK_STY Twin1b LEUK_NSP Twin1b_LEUK_STY Twin1_REM_NSP Twin1_REM_STY Twin2a_LEUK_NSP Twin2a_LEUK_STY Twin2a_REM_NSP Twin2a_REM_STY Twin2b_LEUK_NSP Twin2b_LEUK_STY Twin2b_REM_NSP Twin2b_REM_STY Twin3a_LEUK_NSP Twin3a_LEUK_STY Twin3b_LEUK_NSP Twin3b_LEUK_STY Twin4a_LEUK_NSP Twin4a_LEUK_STY Twin4a_REM_NSP Twin4a_REM_STY Twin4b_LEUK_NSP Twin4b_LEUK_STY Twin5a_LEUK_NSP Twin5a_LEUK_STY Twin5a_REM_NSP Twin5a_REM_STY Twin5b_LEUK_NSP Twin5b_LEUK_STY Twin6a_LEUK_NSP Twin6a_LEUK_STY Twin6a_REM_NSP Twin6a_REM_STY |