The origin and nature of tightly clustered BTG1 deletions in precursor B-cell acute lymphoblastic leukemia support a model of multiclonal evolution.

PLoS Genetics
Esmé WaandersRoland P Kuiper

Abstract

Recurrent submicroscopic deletions in genes affecting key cellular pathways are a hallmark of pediatric acute lymphoblastic leukemia (ALL). To gain more insight into the mechanism underlying these deletions, we have studied the occurrence and nature of abnormalities in one of these genes, the B-cell translocation gene 1 (BTG1), in a large cohort of pediatric ALL cases. BTG1 was found to be exclusively affected by genomic deletions, which were detected in 65 out of 722 B-cell precursor ALL (BCP-ALL) patient samples (9%), but not in 109 T-ALL cases. Eight different deletion sizes were identified, which all clustered at the telomeric site in a hotspot region within the second (and last) exon of the BTG1 gene, resulting in the expression of truncated BTG1 read-through transcripts. The presence of V(D)J recombination signal sequences at both sites of virtually all deletions strongly suggests illegitimate RAG1/RAG2-mediated recombination as the responsible mechanism. Moreover, high levels of histone H3 lysine 4 trimethylation (H3K4me3), which is known to tether the RAG enzyme complex to DNA, were found within the BTG1 gene body in BCP-ALL cells, but not T-ALL cells. BTG1 deletions were rarely found in hyperdiploid BCP-ALLs, but were ...Continue Reading

References

Jan 10, 2002·The Journal of Experimental Medicine·Rodrig MarculescuBertrand Nadel
Sep 25, 2003·Nature Reviews. Molecular Cell Biology·Michael R LieberKlaus Schwarz
Apr 9, 2004·The New England Journal of Medicine·Ching-Hon PuiJames R Downing
Oct 21, 2004·Genes, Chromosomes & Cancer·Sascha RaschkeAndrea R Florl
Mar 23, 2006·Annual Review of Immunology·David JungFrederick W Alt
Mar 9, 2007·Nature·Charles G MullighanJames R Downing
Nov 23, 2007·Nature·Adam G W MatthewsMarjorie A Oettinger
Mar 29, 2008·Annual Review of Immunology·Janet StavnezerCarol E Schrader
Apr 15, 2008·Nature·Charles G MullighanJames R Downing
Nov 29, 2008·Science·Charles G MullighanJames R Downing
Sep 12, 2009·Journal of Cellular Physiology·G Sebastiaan Winkler
Apr 1, 2010·Blood·Joost C van GalenFrank N van Leeuwen
Apr 3, 2010·Seminars in Cancer Biology·Mel Greaves
Oct 30, 2010·Biochemical and Biophysical Research Communications·Masashi NumataKyosuke Nagata
Apr 13, 2011·Blood·Frederik W van DelftMel Greaves
Jul 29, 2011·Nature·Ryan D MorinMarco A Marra

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Citations

Jan 30, 2014·Nature Genetics·Roland P Kuiper, Esmé Waanders
Jul 2, 2014·Cellular Oncology (Dordrecht)·Ad Geurts van Kessel
Sep 24, 2013·Genome Research·Nicola E PotterMel Greaves
Oct 3, 2013·International Journal of Molecular Sciences·Yang ZhaoHua-Chuan Zheng
May 29, 2015·Leukemia·A M FordM Greaves
Nov 19, 2014·International Journal of Oncology·Mitsuro KandaYasuhiro Kodera
May 29, 2016·Chinese Journal of Cancer·Zhi-Jie KangQuentin Liu
May 16, 2017·Genes·Candace J Poole, Jan van Riggelen
Mar 21, 2018·Leukemia·Caroline L FurnessMel Greaves
Apr 20, 2018·Bone Marrow Transplantation·Mary HorowitzNicolaus Kröger
Oct 24, 2018·Journal of Cellular Physiology·Laurensia YuniatiFrank N van Leeuwen
Mar 29, 2019·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Rosario Francisco-VelillaEncarnacion Martinez-Salas
Dec 5, 2018·Blood·Marie PassetUNKNOWN Group for Research on Adult ALL (GRAALL)
Dec 15, 2015·Oncotarget·Laurensia YuniatiFrank N van Leeuwen
Jul 16, 2016·Oncotarget·Bruno Almeida LopesMariana Emerenciano
Aug 26, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Katarina Ochodnicka-MackovicovaJeroen E J Guikema
Jul 22, 2019·International Journal of Molecular Sciences·Jeong Sook KimByung Seok Lee
Mar 14, 2020·Science·Soo Seok HwangRichard A Flavell
Sep 28, 2017·Cancer Prevention Research·Bruno A LopesUNKNOWN Brazilian Study Group for Childhood Leukemia

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Methods Mentioned

BETA
PCR
acetylation
immunoprecipitation
ChIP
PCRs
genotyping
transfection

Software Mentioned

SPSS
Hapmap
Affymetrix Genotyping Console
VectorNTI
Vector NTI
Vector NTI software
MeltIngeny
Nexus
Invitrogen

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