TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study

PanCareLIFE Consortium; CPNDS Consortium; A. J. M. Meijer; F. A. Diepstraten; T. Langer; L. Broer; I. K. Domingo; E. Clemens; A. G. Uitterlinden; A. C. H. de Vries; M. van Grotel; W. P. Vermeij; R. A. Ozinga; H. Binder; J. Byrne; E. van Dulmen-den Broeder; M. L. Garre; D. Grabow; P. Kaatsch; M. Kaiser; L. Kenborg; J. F. Winther; C. Rechnitzer; H. Hasle; T. Kepak; K. Kepakova; W. J. E. Tissing; A. L. F. van der Kooi; L. C. M. Kremer; J. Kruseova; S. M. F. Pluijm; C. E. Kuehni; H. J. H. van der Pal; R. Parfitt; C. Spix; A. Tillmanns; D. Deuster; P. Matulat; G. Calaminus; A. E. Hoetink; S. Elsner; J. Gebauer; R. Haupt; H. Lackner; C. Blattmann; S. J. C. M. M. Neggers; S. R. Rassekh; G. E. B. Wright; B. Brooks; A. P. Nagtegaal; B. I. Drogemoller; C. J. D. Ross; A.P. Bhavsar; Antoinette Am Zehnhoff-Dinnesen; Bruce C. Carleton; O Zolk; MarryM. van den Heuvel-Eibrink

doi:10.1038/s41698-021-00178-z

TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study

PanCareLIFE Consortium, CPNDS Consortium, A. J. M. Meijer^*, F. A. Diepstraten, T. Langer, L. Broer, I. K. Domingo, E. Clemens, A. G. Uitterlinden, A. C. H. de Vries, M. van Grotel, W. P. Vermeij, R. A. Ozinga, H. Binder, J. Byrne, E. van Dulmen-den Broeder, M. L. Garre, D. Grabow, P. Kaatsch, M. KaiserL. Kenborg, J. F. Winther, C. Rechnitzer, H. Hasle, T. Kepak, K. Kepakova, W. J. E. Tissing, A. L. F. van der Kooi, L. C. M. Kremer, J. Kruseova, S. M. F. Pluijm, C. E. Kuehni, H. J. H. van der Pal, R. Parfitt, C. Spix, A. Tillmanns, D. Deuster, P. Matulat, G. Calaminus, A. E. Hoetink, S. Elsner, J. Gebauer, R. Haupt, H. Lackner, C. Blattmann, S. J. C. M. M. Neggers, S. R. Rassekh, G. E. B. Wright, B. Brooks, A. P. Nagtegaal, B. I. Drogemoller, C. J. D. Ross, A.P. Bhavsar, Antoinette Am Zehnhoff-Dinnesen, Bruce C. Carleton, O Zolk, MarryM. van den Heuvel-Eibrink

^*Corresponding author for this work

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Abstract

In children with cancer, the heterogeneity in ototoxicity occurrence after similar treatment suggests a role for genetic susceptibility. Using a genome-wide association study (GWAS) approach, we identified a genetic variant in TCERG1L (rs893507) to be associated with hearing loss in 390 non-cranial irradiated, cisplatin-treated children with cancer. These results were replicated in two independent, similarly treated cohorts (n = 192 and 188, respectively) (combined cohort: P= 5.3 x 10(-10), OR 3.11, 95% CI 2.2-4.5). Modulating TCERG1L expression in cultured human cells revealed significantly altered cellular responses to cisplatin-induced cytokine secretion and toxicity. These results contribute to insights into the genetic and pathophysiological basis of cisplatin-induced ototoxicity.

Original language	English
Article number	64
Pages (from-to)	1-8
Number of pages	8
Journal	NPJ precision oncology
Volume	5
Issue number	1
DOIs	https://doi.org/10.1038/s41698-021-00178-z
Publication status	Published - 14-Jul-2021

Keywords

DNA HYPERMETHYLATION
OTOTOXICITY
CHILDREN
TOXICITY
CELLS
PANEL

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TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE studyFinal publisher's version, 1.49 MBLicence: CC BY

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PanCareLIFE Consortium, CPNDS Consortium, Meijer, A. J. M., Diepstraten, F. A., Langer, T., Broer, L., Domingo, I. K., Clemens, E., Uitterlinden, A. G., de Vries, A. C. H., van Grotel, M., Vermeij, W. P., Ozinga, R. A., Binder, H., Byrne, J., van Dulmen-den Broeder, E., Garre, M. L., Grabow, D., Kaatsch, P., ... van den Heuvel-Eibrink, M. (2021). TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study. NPJ precision oncology, 5(1), 1-8. Article 64. https://doi.org/10.1038/s41698-021-00178-z

@article{38708d232a90420c9f174d25cd4e5a4f,

title = "TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study",

abstract = "In children with cancer, the heterogeneity in ototoxicity occurrence after similar treatment suggests a role for genetic susceptibility. Using a genome-wide association study (GWAS) approach, we identified a genetic variant in TCERG1L (rs893507) to be associated with hearing loss in 390 non-cranial irradiated, cisplatin-treated children with cancer. These results were replicated in two independent, similarly treated cohorts (n = 192 and 188, respectively) (combined cohort: P= 5.3 x 10(-10), OR 3.11, 95% CI 2.2-4.5). Modulating TCERG1L expression in cultured human cells revealed significantly altered cellular responses to cisplatin-induced cytokine secretion and toxicity. These results contribute to insights into the genetic and pathophysiological basis of cisplatin-induced ototoxicity.",

keywords = "DNA HYPERMETHYLATION, OTOTOXICITY, CHILDREN, TOXICITY, CELLS, PANEL",

author = "{PanCareLIFE Consortium} and {CPNDS Consortium} and Meijer, {A. J. M.} and Diepstraten, {F. A.} and T. Langer and L. Broer and Domingo, {I. K.} and E. Clemens and Uitterlinden, {A. G.} and {de Vries}, {A. C. H.} and {van Grotel}, M. and Vermeij, {W. P.} and Ozinga, {R. A.} and H. Binder and J. Byrne and {van Dulmen-den Broeder}, E. and Garre, {M. L.} and D. Grabow and P. Kaatsch and M. Kaiser and L. Kenborg and Winther, {J. F.} and C. Rechnitzer and H. Hasle and T. Kepak and K. Kepakova and Tissing, {W. J. E.} and {van der Kooi}, {A. L. F.} and Kremer, {L. C. M.} and J. Kruseova and Pluijm, {S. M. F.} and Kuehni, {C. E.} and {van der Pal}, {H. J. H.} and R. Parfitt and C. Spix and A. Tillmanns and D. Deuster and P. Matulat and G. Calaminus and Hoetink, {A. E.} and S. Elsner and J. Gebauer and R. Haupt and H. Lackner and C. Blattmann and Neggers, {S. J. C. M. M.} and Rassekh, {S. R.} and Wright, {G. E. B.} and B. Brooks and Nagtegaal, {A. P.} and Drogemoller, {B. I.} and Ross, {C. J. D.} and A.P. Bhavsar and Zehnhoff-Dinnesen, {Antoinette Am} and Carleton, {Bruce C.} and O Zolk and {van den Heuvel-Eibrink}, MarryM.",

year = "2021",

month = jul,

day = "14",

doi = "10.1038/s41698-021-00178-z",

language = "English",

volume = "5",

pages = "1--8",

journal = "NPJ precision oncology",

issn = "2397-768X",

publisher = " Nature Research ",

number = "1",

}

PanCareLIFE Consortium, CPNDS Consortium, Meijer, AJM, Diepstraten, FA, Langer, T, Broer, L, Domingo, IK, Clemens, E, Uitterlinden, AG, de Vries, ACH, van Grotel, M, Vermeij, WP, Ozinga, RA, Binder, H, Byrne, J, van Dulmen-den Broeder, E, Garre, ML, Grabow, D, Kaatsch, P, Kaiser, M, Kenborg, L, Winther, JF, Rechnitzer, C, Hasle, H, Kepak, T, Kepakova, K, Tissing, WJE, van der Kooi, ALF, Kremer, LCM, Kruseova, J, Pluijm, SMF, Kuehni, CE, van der Pal, HJH, Parfitt, R, Spix, C, Tillmanns, A, Deuster, D, Matulat, P, Calaminus, G, Hoetink, AE, Elsner, S, Gebauer, J, Haupt, R, Lackner, H, Blattmann, C, Neggers, SJCMM, Rassekh, SR, Wright, GEB, Brooks, B, Nagtegaal, AP, Drogemoller, BI, Ross, CJD, Bhavsar, AP, Zehnhoff-Dinnesen, AA, Carleton, BC, Zolk, O & van den Heuvel-Eibrink, M 2021, 'TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study', NPJ precision oncology, vol. 5, no. 1, 64, pp. 1-8. https://doi.org/10.1038/s41698-021-00178-z

TY - JOUR

T1 - TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study

AU - PanCareLIFE Consortium

AU - CPNDS Consortium

AU - Meijer, A. J. M.

AU - Diepstraten, F. A.

AU - Langer, T.

AU - Broer, L.

AU - Domingo, I. K.

AU - Clemens, E.

AU - Uitterlinden, A. G.

AU - de Vries, A. C. H.

AU - van Grotel, M.

AU - Vermeij, W. P.

AU - Ozinga, R. A.

AU - Binder, H.

AU - Byrne, J.

AU - van Dulmen-den Broeder, E.

AU - Garre, M. L.

AU - Grabow, D.

AU - Kaatsch, P.

AU - Kaiser, M.

AU - Kenborg, L.

AU - Winther, J. F.

AU - Rechnitzer, C.

AU - Hasle, H.

AU - Kepak, T.

AU - Kepakova, K.

AU - Tissing, W. J. E.

AU - van der Kooi, A. L. F.

AU - Kremer, L. C. M.

AU - Kruseova, J.

AU - Pluijm, S. M. F.

AU - Kuehni, C. E.

AU - van der Pal, H. J. H.

AU - Parfitt, R.

AU - Spix, C.

AU - Tillmanns, A.

AU - Deuster, D.

AU - Matulat, P.

AU - Calaminus, G.

AU - Hoetink, A. E.

AU - Elsner, S.

AU - Gebauer, J.

AU - Haupt, R.

AU - Lackner, H.

AU - Blattmann, C.

AU - Neggers, S. J. C. M. M.

AU - Rassekh, S. R.

AU - Wright, G. E. B.

AU - Brooks, B.

AU - Nagtegaal, A. P.

AU - Drogemoller, B. I.

AU - Ross, C. J. D.

AU - Bhavsar, A.P.

AU - Zehnhoff-Dinnesen, Antoinette Am

AU - Carleton, Bruce C.

AU - Zolk, O

AU - van den Heuvel-Eibrink, MarryM.

PY - 2021/7/14

Y1 - 2021/7/14

N2 - In children with cancer, the heterogeneity in ototoxicity occurrence after similar treatment suggests a role for genetic susceptibility. Using a genome-wide association study (GWAS) approach, we identified a genetic variant in TCERG1L (rs893507) to be associated with hearing loss in 390 non-cranial irradiated, cisplatin-treated children with cancer. These results were replicated in two independent, similarly treated cohorts (n = 192 and 188, respectively) (combined cohort: P= 5.3 x 10(-10), OR 3.11, 95% CI 2.2-4.5). Modulating TCERG1L expression in cultured human cells revealed significantly altered cellular responses to cisplatin-induced cytokine secretion and toxicity. These results contribute to insights into the genetic and pathophysiological basis of cisplatin-induced ototoxicity.

AB - In children with cancer, the heterogeneity in ototoxicity occurrence after similar treatment suggests a role for genetic susceptibility. Using a genome-wide association study (GWAS) approach, we identified a genetic variant in TCERG1L (rs893507) to be associated with hearing loss in 390 non-cranial irradiated, cisplatin-treated children with cancer. These results were replicated in two independent, similarly treated cohorts (n = 192 and 188, respectively) (combined cohort: P= 5.3 x 10(-10), OR 3.11, 95% CI 2.2-4.5). Modulating TCERG1L expression in cultured human cells revealed significantly altered cellular responses to cisplatin-induced cytokine secretion and toxicity. These results contribute to insights into the genetic and pathophysiological basis of cisplatin-induced ototoxicity.

KW - DNA HYPERMETHYLATION

KW - OTOTOXICITY

KW - CHILDREN

KW - TOXICITY

KW - CELLS

KW - PANEL

U2 - 10.1038/s41698-021-00178-z

DO - 10.1038/s41698-021-00178-z

M3 - Article

SN - 2397-768X

VL - 5

SP - 1

EP - 8

JO - NPJ precision oncology

JF - NPJ precision oncology

IS - 1

M1 - 64

ER -

TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study

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Keywords

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