Evolutionary trajectories of hyperdiploid ALL in monozygotic twins
- 4 June 2014
- journal article
- research article
- Published by Springer Science and Business Media LLC in Leukemia
- Vol. 29 (1), 58-65
- https://doi.org/10.1038/leu.2014.177
Abstract
Identical twins have provided unique insights on timing or sequence of genetic events in acute lymphoblastic leukaemia (ALL). To date, this has mainly focused on ALL with MLL or ETV6-RUNX1 fusions, with hyperdiploid ALL remaining less well characterised. We examined three pairs of monozygotic twins, two concordant and one discordant for hyperdiploid ALL, for single-nucleotide polymorphism (SNP)-defined copy number alterations (CNAs), IGH/L plus TCR gene rearrangements and mutations in NRAS, KRAS, FLT3 and PTPN11 genes. We performed whole exome sequencing in one concordant twin pair. Potential ‘driver’ CNAs were low, 0–3 per case, and all were different within a pair. One patient had an NRAS mutation that was lacking from leukaemic cells of the twin sibling. By exome sequencing, there were 12 nonsynonymous mutations found in one twin and 5 in the other, one of which in SCL44A2 was shared or identical. Concordant pairs had some identical IGH/L and TCR rearrangements. In the twin pair with discordant hyperdiploid ALL, the healthy co-twin had persistent low level hyperdiploid CD19+ cells that lacked a CNA present in the ALL cells of her sibling. From these data, we propose that hyperdiploid ALL arises in a pre-B cell in utero and mutational changes necessary for clinical ALL accumulate subclonally and postnatally.Keywords
This publication has 40 references indexed in Scilit:
- High modal number and triple trisomies are highly correlated favorable factors in childhood B-cell precursor high hyperdiploid acute lymphoblastic leukemia treated according to the NOPHO ALL 1992/2000 protocolsHaematologica, 2013
- Developmental timing of mutations revealed by whole-genome sequencing of twins with acute lymphoblastic leukemiaProceedings of the National Academy of Sciences of the United States of America, 2013
- EuroClonality/BIOMED-2 guidelines for interpretation and reporting of Ig/TCR clonality testing in suspected lymphoproliferationsLeukemia, 2012
- The Origin and Evolution of Mutations in Acute Myeloid LeukemiaCell, 2012
- Developmental origins and impact of BCR-ABL1 fusion and IKZF1 deletions in monozygotic twins with Ph+ acute lymphoblastic leukemiaBlood, 2011
- Genetic landscape of high hyperdiploid childhood acute lymphoblastic leukemiaProceedings of the National Academy of Sciences, 2010
- Backtracking RAS mutations in high hyperdiploid childhood acute lymphoblastic leukemiaBlood Cells, Molecules, and Diseases, 2010
- The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing dataGenome Research, 2010
- A global network of transcription factors, involving E2A, EBF1 and Foxo1, that orchestrates B cell fateNature Immunology, 2010
- Microdeletions are a general feature of adult and adolescent acute lymphoblastic leukemia: Unexpected similarities with pediatric diseaseProceedings of the National Academy of Sciences of the United States of America, 2008