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Is cancer latency an outdated concept? Lessons from chronic myeloid leukemia

Is cancer latency an outdated concept? Lessons from chronic myeloid leukemia
Is cancer latency an outdated concept? Lessons from chronic myeloid leukemia
Our concept of cancer latency, the interval from when a cancer starts until it is diagnosed, has changed dramatically. A prior widely-used definition was the interval between an exposure to a cancer-causing substance and cancer diagnosis. However, this definition does not accurately reflect current knowledge of how most cancers develop assuming, mostly incorrectly, one exposure is the sole cause of a cancer, ignoring the possibility the cancer being considered would have developed anyway but that the exposure accelerated cancer development and eliding the randomness in when a cancer is diagnosed. We show, using chronic myeloid leukaemia as a model, that defining cancer latency is not as simple as it once seemed. It is difficult or impossible to know at which event or mutation to start to clock to measure cancer latency. It is equally difficult to know when to stop the clock given the stochastic nature of when cancers are diagnosed. Importantly, even in genetically-identical twins with the same driver mutation intervals to develop cancer vary substantially. And we discuss other confonders. Clearly we need a new definition of cancer latency or we need to abandon the concept of cancer latency in the modern era of cancer biology.
0887-6924
2279-2284
Abecasis, Manuel
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Cross, Nicholas C.P.
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Brito, Manuel
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Ferreira, Isabelina
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Sakamoto, Kathleen M.
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Hijiya, Nobuko
909719be-c046-4ce3-baac-4f4fadace86a
Score, Joannah
376ca13f-2b1b-43b5-aefa-da1d82291615
Gale, Robert Peter
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Abecasis, Manuel
50b3ee39-eba6-4e5b-96b6-ee33e26f3d71
Cross, Nicholas C.P.
f87650da-b908-4a34-b31b-d62c5f186fe4
Brito, Manuel
19f424fa-64f5-4539-820b-96e6ba75f055
Ferreira, Isabelina
a3bbbd1b-5459-4cdb-98ed-5787f0a45682
Sakamoto, Kathleen M.
7b9de60f-aa39-4b02-88dc-6106c79d522a
Hijiya, Nobuko
909719be-c046-4ce3-baac-4f4fadace86a
Score, Joannah
376ca13f-2b1b-43b5-aefa-da1d82291615
Gale, Robert Peter
f07d8cc8-781d-4eb3-b920-48c4dcdb8c77

Abecasis, Manuel, Cross, Nicholas C.P., Brito, Manuel, Ferreira, Isabelina, Sakamoto, Kathleen M., Hijiya, Nobuko, Score, Joannah and Gale, Robert Peter (2020) Is cancer latency an outdated concept? Lessons from chronic myeloid leukemia. Leukemia, 34 (9), 2279-2284. (doi:10.1038/s41375-020-0957-z).

Record type: Article

Abstract

Our concept of cancer latency, the interval from when a cancer starts until it is diagnosed, has changed dramatically. A prior widely-used definition was the interval between an exposure to a cancer-causing substance and cancer diagnosis. However, this definition does not accurately reflect current knowledge of how most cancers develop assuming, mostly incorrectly, one exposure is the sole cause of a cancer, ignoring the possibility the cancer being considered would have developed anyway but that the exposure accelerated cancer development and eliding the randomness in when a cancer is diagnosed. We show, using chronic myeloid leukaemia as a model, that defining cancer latency is not as simple as it once seemed. It is difficult or impossible to know at which event or mutation to start to clock to measure cancer latency. It is equally difficult to know when to stop the clock given the stochastic nature of when cancers are diagnosed. Importantly, even in genetically-identical twins with the same driver mutation intervals to develop cancer vary substantially. And we discuss other confonders. Clearly we need a new definition of cancer latency or we need to abandon the concept of cancer latency in the modern era of cancer biology.

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abecasis v30 - Accepted Manuscript
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Accepted/In Press date: 25 June 2020
e-pub ahead of print date: 6 July 2020
Published date: 1 September 2020

Identifiers

Local EPrints ID: 443301
URI: http://eprints.soton.ac.uk/id/eprint/443301
ISSN: 0887-6924
PURE UUID: 89872205-cb07-451f-a8f4-b1b1949f8f51
ORCID for Nicholas C.P. Cross: ORCID iD orcid.org/0000-0001-5481-2555

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Date deposited: 20 Aug 2020 16:30
Last modified: 28 Apr 2022 06:32

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Contributors

Author: Manuel Abecasis
Author: Manuel Brito
Author: Isabelina Ferreira
Author: Kathleen M. Sakamoto
Author: Nobuko Hijiya
Author: Joannah Score
Author: Robert Peter Gale

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