Molecular Ontogeny of Donor-Derived Follicular Lymphomas Occurring after Hematopoietic Cell Transplantation
Open Access
- 1 January 2012
- journal article
- case report
- Published by American Association for Cancer Research (AACR) in Cancer Discovery
- Vol. 2 (1), 47-55
- https://doi.org/10.1158/2159-8290.cd-11-0208
Abstract
The relative timing of genetic alterations that contribute to follicular lymphoma remains unknown. We analyzed a donor–recipient pair who both developed grade 2/3A follicular lymphoma 7 years after allogeneic transplantation and donor lymphocyte infusions. Both patients harbored identical BCL2/IGH rearrangements also present in 1 in 2,000 cells in the donor lymphocyte infusion, and the same V(D)J rearrangement, which underwent somatic hypermutation both before and after clonal divergence. Exome sequencing of both follicular lymphomas identified 15 shared mutations, of which 14 (including alterations in EP300 and KLHL6) were recovered from the donor lymphocyte infusion by ultra-deep sequencing (average read coverage, 361,723), indicating acquisition at least 7 years before clinical presentation. Six additional mutations were present in only one follicular lymphoma and not the donor lymphocyte infusion, including an ARID1A premature stop, indicating later acquisition during clonal divergence. Thus, ultrasensitive sequencing can map clonal evolution within rare subpopulations during human lymphomagenesis in vivo. Significance: For the first time, we define the molecular ontogeny of follicular lymphoma during clonal evolution in vivo. By using ultrasensitive mutation detection, we mapped the time-course of somatic alterations after passage of a malignant ancestor by hematopoietic cell transplantation. Cancer Discovery; 2(1); 47–55. ©2011 AACR. This article is highlighted in the In This Issue feature, p. 1Other Versions
This publication has 27 references indexed in Scilit:
- Frequent mutation of histone-modifying genes in non-Hodgkin lymphomaNature, 2011
- Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemiaNature, 2011
- Inactivating mutations of acetyltransferase genes in B-cell lymphomaNature, 2011
- COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in CancerNucleic Acids Research, 2010
- ARID1AMutations in Endometriosis-Associated Ovarian CarcinomasThe New England Journal of Medicine, 2010
- Frequent Mutations of Chromatin Remodeling Gene ARID1A in Ovarian Clear Cell CarcinomaScience, 2010
- Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center originNature Genetics, 2010
- Human Chromosomal Translocations at CpG Sites and a Theoretical Basis for Their Lineage and Stage SpecificityCell, 2008
- DNA sequencing of a cytogenetically normal acute myeloid leukaemia genomeNature, 2008
- Follicular lymphoma-like B cells in healthy individuals: a novel intermediate step in early lymphomagenesisThe Journal of Experimental Medicine, 2006