Whole chromosome gain does not in itself confer cancer-like chromosomal instability.
Valind, Anders LU
; Jin, Yuesheng
LU
; Baldetorp, Bo
LU
and Gisselsson Nord, David
LU
(2013)
In Proceedings of the National Academy of Sciences
110(52).
p.21119-21123
- Abstract
- Constitutional aneuploidy is typically caused by a single-event meiotic or early mitotic error. In contrast, somatic aneuploidy, found mainly in neoplastic tissue, is attributed to continuous chromosomal instability. More debated as a cause of aneuploidy is aneuploidy itself; that is, whether aneuploidy per se causes chromosomal instability, for example, in patients with inborn aneuploidy. We have addressed this issue by quantifying the level of somatic mosaicism, a proxy marker of chromosomal instability, in patients with constitutional aneuploidy by precise background-filtered dual-color FISH. In contrast to previous studies that used less precise methods, we find that constitutional trisomy, even for large chromosomes that are often... (More)
- Constitutional aneuploidy is typically caused by a single-event meiotic or early mitotic error. In contrast, somatic aneuploidy, found mainly in neoplastic tissue, is attributed to continuous chromosomal instability. More debated as a cause of aneuploidy is aneuploidy itself; that is, whether aneuploidy per se causes chromosomal instability, for example, in patients with inborn aneuploidy. We have addressed this issue by quantifying the level of somatic mosaicism, a proxy marker of chromosomal instability, in patients with constitutional aneuploidy by precise background-filtered dual-color FISH. In contrast to previous studies that used less precise methods, we find that constitutional trisomy, even for large chromosomes that are often trisomic in cancer, does not confer a significantly elevated rate of somatic chromosomal mosaicism in individual cases. Constitutional triploidy was associated with an increased level of somatic mosaicism, but this consisted mostly of reversion from trisomy to disomy and did not correspond to a proportionally elevated level of chromosome mis-segregation in triploids, indicating that the observed mosaicism resulted from a specific accumulation of cells with a hypotriploid chromosome number. In no case did the rate of somatic mosaicism in constitutional aneuploidy exceed that of "chromosomally stable" cancer cells. Our findings show that even though constitutional aneuploidy was in some cases associated with low-level somatic mosaicism, it was insufficient to generate the cancer-like levels expected if aneuploidy single-handedly triggered cancer-like chromosomal instability. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4224930
- author
- Valind, Anders
LU
; Jin, Yuesheng
LU
; Baldetorp, Bo
LU
and Gisselsson Nord, David
LU
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Proceedings of the National Academy of Sciences
- volume
- 110
- issue
- 52
- pages
- 21119 - 21123
- publisher
- National Academy of Sciences
- external identifiers
-
- wos:000328858800064
- pmid:24324169
- scopus:84891363070
- pmid:24324169
- ISSN
- 1091-6490
- DOI
- 10.1073/pnas.1311163110
- language
- English
- LU publication?
- yes
- id
- bccd38d8-cc7b-4329-90d0-8fe0732c440a (old id 4224930)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/24324169?dopt=Abstract
- date added to LUP
- 2016-04-01 10:30:46
- date last changed
- 2022-04-27 22:47:36
@article{bccd38d8-cc7b-4329-90d0-8fe0732c440a,
abstract = {{Constitutional aneuploidy is typically caused by a single-event meiotic or early mitotic error. In contrast, somatic aneuploidy, found mainly in neoplastic tissue, is attributed to continuous chromosomal instability. More debated as a cause of aneuploidy is aneuploidy itself; that is, whether aneuploidy per se causes chromosomal instability, for example, in patients with inborn aneuploidy. We have addressed this issue by quantifying the level of somatic mosaicism, a proxy marker of chromosomal instability, in patients with constitutional aneuploidy by precise background-filtered dual-color FISH. In contrast to previous studies that used less precise methods, we find that constitutional trisomy, even for large chromosomes that are often trisomic in cancer, does not confer a significantly elevated rate of somatic chromosomal mosaicism in individual cases. Constitutional triploidy was associated with an increased level of somatic mosaicism, but this consisted mostly of reversion from trisomy to disomy and did not correspond to a proportionally elevated level of chromosome mis-segregation in triploids, indicating that the observed mosaicism resulted from a specific accumulation of cells with a hypotriploid chromosome number. In no case did the rate of somatic mosaicism in constitutional aneuploidy exceed that of "chromosomally stable" cancer cells. Our findings show that even though constitutional aneuploidy was in some cases associated with low-level somatic mosaicism, it was insufficient to generate the cancer-like levels expected if aneuploidy single-handedly triggered cancer-like chromosomal instability.}},
author = {{Valind, Anders and Jin, Yuesheng and Baldetorp, Bo and Gisselsson Nord, David}},
issn = {{1091-6490}},
language = {{eng}},
number = {{52}},
pages = {{21119--21123}},
publisher = {{National Academy of Sciences}},
series = {{Proceedings of the National Academy of Sciences}},
title = {{Whole chromosome gain does not in itself confer cancer-like chromosomal instability.}},
url = {{http://dx.doi.org/10.1073/pnas.1311163110}},
doi = {{10.1073/pnas.1311163110}},
volume = {{110}},
year = {{2013}},
}