Elevated Mutational Age in Blood of Children Treated for Cancer Contributes to Therapy-Related Myeloid Neoplasms (Record no. 785)
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042 ## - AUTHENTICATION CODE | |
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Authentication code | dc |
100 10 - MAIN ENTRY--PERSONAL NAME | |
Personal name | Bertrums, Eline J.M. |
Relator term | author |
9 (RLIN) | 1254 |
245 00 - TITLE STATEMENT | |
Title | Elevated Mutational Age in Blood of Children Treated for Cancer Contributes to Therapy-Related Myeloid Neoplasms |
260 ## - PUBLICATION, DISTRIBUTION, ETC. | |
Name of publisher, distributor, etc. | American Association for Cancer Research, |
Date of publication, distribution, etc. | 2022-08-05. |
500 ## - GENERAL NOTE | |
General note | /pmc/articles/PMC7613255/ |
500 ## - GENERAL NOTE | |
General note | /pubmed/35678530 |
520 ## - SUMMARY, ETC. | |
Summary, etc. | Childhood cancer survivors are confronted with various chronic health conditions like therapy-related malignancies. However, it is unclear how exposure to chemotherapy contributes to the mutation burden and clonal composition of healthy tissues early in life. Here, we studied mutation accumulation in hematopoietic stem and progenitor cells (HSPC) before and after cancer treatment of 24 children. Of these children, 19 developed therapy-related myeloid neoplasms (t-MN). Posttreatment HSPCs had an average mutation burden increase comparable to what treatment-naïve cells accumulate during 16 years of life, with excesses up to 80 years. In most children, these additional mutations were induced by clock-like processes, which are also active during healthy aging. Other patients harbored mutations that could be directly attributed to treatments like platinum-based drugs and thiopurines. Using phylogenetic inference, we demonstrate that most t-MN in children originate after the start of treatment and that leukemic clones become dominant during or directly after chemotherapy exposure. SIGNIFICANCE: Our study shows that chemotherapy increases the mutation burden of normal blood cells in cancer survivors. Only few drugs damage the DNA directly, whereas in most patients, chemotherapy-induced mutations are caused by processes similar to those present during normal aging. This article is highlighted in the In This Issue feature, p. 1825 |
540 ## - TERMS GOVERNING USE AND REPRODUCTION NOTE | |
Terms governing use and reproduction | ©2022 The Authors; Published by the American Association for Cancer Research |
540 ## - TERMS GOVERNING USE AND REPRODUCTION NOTE | |
Terms governing use and reproduction | https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license. |
546 ## - LANGUAGE NOTE | |
Language note | en |
690 ## - LOCAL SUBJECT ADDED ENTRY--TOPICAL TERM (OCLC, RLIN) | |
Topical term or geographic name as entry element | Research Briefs |
9 (RLIN) | 1267 |
655 7# - INDEX TERM--GENRE/FORM | |
Genre/form data or focus term | Text |
Source of term | local |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Rosendahl Huber, Axel K.M. |
Relator term | author |
9 (RLIN) | 1255 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | de Kanter, Jurrian K. |
Relator term | author |
9 (RLIN) | 1256 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Brandsma, Arianne M. |
Relator term | author |
9 (RLIN) | 1257 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | van Leeuwen, Anaïs J.C.N. |
Relator term | author |
9 (RLIN) | 1258 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Verheul, Mark |
Relator term | author |
9 (RLIN) | 1259 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | van den Heuvel-Eibrink, Marry M. |
Relator term | author |
9 (RLIN) | 1260 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Oka, Rurika |
Relator term | author |
9 (RLIN) | 1261 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | van Roosmalen, Markus J. |
Relator term | author |
9 (RLIN) | 1262 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | de Groot-Kruseman, Hester A. |
Relator term | author |
9 (RLIN) | 1263 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Zwaan, C. Michel |
Relator term | author |
9 (RLIN) | 1264 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | Goemans, Bianca F. |
Relator term | author |
9 (RLIN) | 1265 |
700 10 - ADDED ENTRY--PERSONAL NAME | |
Personal name | van Boxtel, Ruben |
Relator term | author |
9 (RLIN) | 1266 |
786 0# - DATA SOURCE ENTRY | |
Note | Cancer Discov |
856 41 - ELECTRONIC LOCATION AND ACCESS | |
Uniform Resource Identifier | <a href="http://dx.doi.org/10.1158/2159-8290.CD-22-0120">http://dx.doi.org/10.1158/2159-8290.CD-22-0120</a> |
Public note | Connect to this object online. |
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