Translocation breakpoints preferentially occur in euchromatin and acrocentric chromosomes

Lin, Cheng-Yu, Shukla, Ankit, Grady, John P. , Fink, J. Lynn, Dray, Eloise and Duijf, Pascal H.G. (2018) Translocation breakpoints preferentially occur in euchromatin and acrocentric chromosomes. Cancers, 10 1: . doi:10.3390/cancers10010013

Author Lin, Cheng-Yu
Shukla, Ankit
Grady, John P.
Fink, J. Lynn
Dray, Eloise
Duijf, Pascal H.G.
Title Translocation breakpoints preferentially occur in euchromatin and acrocentric chromosomes
Journal name Cancers   Check publisher's open access policy
ISSN 2072-6694
Publication date 2018-01-08
Year available 2018
Sub-type Article (original research)
DOI 10.3390/cancers10010013
Open Access Status DOI
Volume 10
Issue 1
Total pages 19
Place of publication Basel, Switzerland
Publisher M D P I AG
Language eng
Subject 2730 Oncology
1306 Cancer Research
Abstract Chromosomal translocations drive the development of many hematological and some solid cancers. Several factors have been identified to explain the non-random occurrence of translocation breakpoints in the genome. These include chromatin density, gene density and CCCTC-binding factor (CTCF)/cohesin binding site density. However, such factors are at least partially interdependent. Using 13,844 and 1563 karyotypes from human blood and solid cancers, respectively, our multiple regression analysis only identified chromatin density as the primary statistically significant predictor. Specifically, translocation breakpoints preferentially occur in open chromatin. Also, blood and solid tumors show markedly distinct translocation signatures. Strikingly, translocation breakpoints occur significantly more frequently in acrocentric chromosomes than in non-acrocentric chromosomes. Thus, translocations are probably often generated around nucleoli in the inner nucleoplasm, away from the nuclear envelope. Importantly, our findings remain true both in multivariate analyses and after removal of highly recurrent translocations. Finally, we applied pairwise probabilistic co-occurrence modeling. In addition to well-known highly prevalent translocations, such as those resulting in BCR-ABL1 (BCR-ABL) and RUNX1-RUNX1T1 (AML1-ETO) fusion genes, we identified significantly underrepresented translocations with putative fusion genes, which are probably subject to strong negative selection during tumor evolution. Taken together, our findings provide novel insights into the generation and selection of translocations during cancer development.
Keyword Translocations
DNA double strand breaks
DNA repair
V(D)J recombination
Acrocentric chromosomes
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Mater Research Institute-UQ (MRI-UQ)
HERDC Pre-Audit
UQ Diamantina Institute Publications
Version Filter Type
Citation counts: Scopus Citation Count Cited 0 times in Scopus Article
Google Scholar Search Google Scholar
Created: Thu, 11 Jan 2018, 09:20:16 EST by Pascal Duijf on behalf of UQ Diamantina Institute