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Somatic mutations of DICER1 and KMT2D are frequent in intraocular medulloepitheliomas

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Somatic mutations of DICER1 and KMT2D are frequent in intraocular medulloepitheliomas. / Sahm, Felix; Jakobiec, Frederick A; Meyer, Jochen; Schrimpf, Daniel; Eberhart, Charles G; Hovestadt, Volker; Capper, David; Lambo, Sander; Ryzhova, Marina; Schüller, Ulrich; Zheludkova, Olga; Kumirova, Ella; Lichter, Peter; Deimling, Andreas; Jones, David T W; Pfister, Stefan M; Kool, Marcel; Korshunov, Andrey.

In: GENE CHROMOSOME CANC, Vol. 55, No. 5, 05.2016, p. 418-27.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Sahm, F, Jakobiec, FA, Meyer, J, Schrimpf, D, Eberhart, CG, Hovestadt, V, Capper, D, Lambo, S, Ryzhova, M, Schüller, U, Zheludkova, O, Kumirova, E, Lichter, P, Deimling, A, Jones, DTW, Pfister, SM, Kool, M & Korshunov, A 2016, 'Somatic mutations of DICER1 and KMT2D are frequent in intraocular medulloepitheliomas', GENE CHROMOSOME CANC, vol. 55, no. 5, pp. 418-27. https://doi.org/10.1002/gcc.22344

APA

Sahm, F., Jakobiec, F. A., Meyer, J., Schrimpf, D., Eberhart, C. G., Hovestadt, V., Capper, D., Lambo, S., Ryzhova, M., Schüller, U., Zheludkova, O., Kumirova, E., Lichter, P., Deimling, A., Jones, D. T. W., Pfister, S. M., Kool, M., & Korshunov, A. (2016). Somatic mutations of DICER1 and KMT2D are frequent in intraocular medulloepitheliomas. GENE CHROMOSOME CANC, 55(5), 418-27. https://doi.org/10.1002/gcc.22344

Vancouver

Sahm F, Jakobiec FA, Meyer J, Schrimpf D, Eberhart CG, Hovestadt V et al. Somatic mutations of DICER1 and KMT2D are frequent in intraocular medulloepitheliomas. GENE CHROMOSOME CANC. 2016 May;55(5):418-27. https://doi.org/10.1002/gcc.22344

Bibtex

@article{2d83c39d91e248ff8d5dd940dfadef90,
title = "Somatic mutations of DICER1 and KMT2D are frequent in intraocular medulloepitheliomas",
abstract = "Intraocular medulloepithelioma (IO-MEPL) is an uncommon embryonal neuroepithelial neoplasm of the eye. Little is known about the cytogenetics, molecular biology, and pathogenesis of this tumor. In the present study we investigated the mutational landscape of 19 IO-MEPL using targeted next-generation sequencing. Routinely prepared paraffin-embedded samples were assessed with high-coverage genome sequencing on the Illumina NextSeq 500 platform using a customized gene panel set covering the coding region of 130 genes. This revealed several notable genomic alterations, including mutations of DICER1 (6 tumors) and KMT2D (also known as MLL2; 5 tumors)-which are frequently recurrent and mutually exclusive molecular events for IO-MEPL. Non-recurrent mutations in the cancer-associated genes BRCA2, BRCA1, NOTCH2, CDH1, and GSE1 were also identified. IO-MEPL samples harboring a DICER1 mutation disclosed few chromosomal alterations and formed a separate DNA methylation cluster, indicating potential differences in genetic and epigenetic events arising perhaps from the presence of this aberration in the tumor genome. The high proportion of recurrent somatic DICER1 and KMT2D mutations in this series of sporadic IO-MEPL points to their likely important roles in the molecular pathogenesis of these rare embryonal tumors, and perhaps suggests the existence of distinct molecular variants of IO-MEPL. Although the precise role of these recurrent mutations in the development of IO-MEPL, and their relationship to pro-oncogenic molecular mechanisms, have yet to be determined, unraveling their roles could eventually be exploited for nonsurgical therapies of these neoplasms.",
keywords = "Adolescent, Adult, Child, Child, Preschool, DEAD-box RNA Helicases, DNA-Binding Proteins, Eye Neoplasms, Female, Humans, Infant, Male, Middle Aged, Mutation, Neoplasm Proteins, Neuroectodermal Tumors, Primitive, Ribonuclease III, Journal Article",
author = "Felix Sahm and Jakobiec, {Frederick A} and Jochen Meyer and Daniel Schrimpf and Eberhart, {Charles G} and Volker Hovestadt and David Capper and Sander Lambo and Marina Ryzhova and Ulrich Sch{\"u}ller and Olga Zheludkova and Ella Kumirova and Peter Lichter and Andreas Deimling and Jones, {David T W} and Pfister, {Stefan M} and Marcel Kool and Andrey Korshunov",
note = "{\textcopyright} 2016 Wiley Periodicals, Inc.",
year = "2016",
month = may,
doi = "10.1002/gcc.22344",
language = "English",
volume = "55",
pages = "418--27",
journal = "GENE CHROMOSOME CANC",
issn = "1045-2257",
publisher = "Wiley-Liss Inc.",
number = "5",

}

RIS

TY - JOUR

T1 - Somatic mutations of DICER1 and KMT2D are frequent in intraocular medulloepitheliomas

AU - Sahm, Felix

AU - Jakobiec, Frederick A

AU - Meyer, Jochen

AU - Schrimpf, Daniel

AU - Eberhart, Charles G

AU - Hovestadt, Volker

AU - Capper, David

AU - Lambo, Sander

AU - Ryzhova, Marina

AU - Schüller, Ulrich

AU - Zheludkova, Olga

AU - Kumirova, Ella

AU - Lichter, Peter

AU - Deimling, Andreas

AU - Jones, David T W

AU - Pfister, Stefan M

AU - Kool, Marcel

AU - Korshunov, Andrey

N1 - © 2016 Wiley Periodicals, Inc.

PY - 2016/5

Y1 - 2016/5

N2 - Intraocular medulloepithelioma (IO-MEPL) is an uncommon embryonal neuroepithelial neoplasm of the eye. Little is known about the cytogenetics, molecular biology, and pathogenesis of this tumor. In the present study we investigated the mutational landscape of 19 IO-MEPL using targeted next-generation sequencing. Routinely prepared paraffin-embedded samples were assessed with high-coverage genome sequencing on the Illumina NextSeq 500 platform using a customized gene panel set covering the coding region of 130 genes. This revealed several notable genomic alterations, including mutations of DICER1 (6 tumors) and KMT2D (also known as MLL2; 5 tumors)-which are frequently recurrent and mutually exclusive molecular events for IO-MEPL. Non-recurrent mutations in the cancer-associated genes BRCA2, BRCA1, NOTCH2, CDH1, and GSE1 were also identified. IO-MEPL samples harboring a DICER1 mutation disclosed few chromosomal alterations and formed a separate DNA methylation cluster, indicating potential differences in genetic and epigenetic events arising perhaps from the presence of this aberration in the tumor genome. The high proportion of recurrent somatic DICER1 and KMT2D mutations in this series of sporadic IO-MEPL points to their likely important roles in the molecular pathogenesis of these rare embryonal tumors, and perhaps suggests the existence of distinct molecular variants of IO-MEPL. Although the precise role of these recurrent mutations in the development of IO-MEPL, and their relationship to pro-oncogenic molecular mechanisms, have yet to be determined, unraveling their roles could eventually be exploited for nonsurgical therapies of these neoplasms.

AB - Intraocular medulloepithelioma (IO-MEPL) is an uncommon embryonal neuroepithelial neoplasm of the eye. Little is known about the cytogenetics, molecular biology, and pathogenesis of this tumor. In the present study we investigated the mutational landscape of 19 IO-MEPL using targeted next-generation sequencing. Routinely prepared paraffin-embedded samples were assessed with high-coverage genome sequencing on the Illumina NextSeq 500 platform using a customized gene panel set covering the coding region of 130 genes. This revealed several notable genomic alterations, including mutations of DICER1 (6 tumors) and KMT2D (also known as MLL2; 5 tumors)-which are frequently recurrent and mutually exclusive molecular events for IO-MEPL. Non-recurrent mutations in the cancer-associated genes BRCA2, BRCA1, NOTCH2, CDH1, and GSE1 were also identified. IO-MEPL samples harboring a DICER1 mutation disclosed few chromosomal alterations and formed a separate DNA methylation cluster, indicating potential differences in genetic and epigenetic events arising perhaps from the presence of this aberration in the tumor genome. The high proportion of recurrent somatic DICER1 and KMT2D mutations in this series of sporadic IO-MEPL points to their likely important roles in the molecular pathogenesis of these rare embryonal tumors, and perhaps suggests the existence of distinct molecular variants of IO-MEPL. Although the precise role of these recurrent mutations in the development of IO-MEPL, and their relationship to pro-oncogenic molecular mechanisms, have yet to be determined, unraveling their roles could eventually be exploited for nonsurgical therapies of these neoplasms.

KW - Adolescent

KW - Adult

KW - Child

KW - Child, Preschool

KW - DEAD-box RNA Helicases

KW - DNA-Binding Proteins

KW - Eye Neoplasms

KW - Female

KW - Humans

KW - Infant

KW - Male

KW - Middle Aged

KW - Mutation

KW - Neoplasm Proteins

KW - Neuroectodermal Tumors, Primitive

KW - Ribonuclease III

KW - Journal Article

U2 - 10.1002/gcc.22344

DO - 10.1002/gcc.22344

M3 - SCORING: Journal article

C2 - 26841698

VL - 55

SP - 418

EP - 427

JO - GENE CHROMOSOME CANC

JF - GENE CHROMOSOME CANC

SN - 1045-2257

IS - 5

ER -