Genomic characterization of DICER1-associated neoplasms uncovers molecular classes

Felix K.F. Kommoss; Anne Sophie Chong; Anne Laure Chong; Elke Pfaff; David T.W. Jones; Laura S. Hiemcke-Jiwa; Lennart A. Kester; Uta Flucke; Manfred Gessler; Daniel Schrimpf; Felix Sahm; Blaise A. Clarke; Colin J.R. Stewart; Yemin Wang; C. Blake Gilks; Friedrich Kommoss; David G. Huntsman; Ulrich Schüller; Christian Koelsche; W. Glenn McCluggage; Andreas von Deimling; William D. Foulkes

doi:10.1038/s41467-023-37092-w

Genomic characterization of DICER1-associated neoplasms uncovers molecular classes

Felix K.F. Kommoss, Anne Sophie Chong, Anne Laure Chong, Elke Pfaff, David T.W. Jones, Laura S. Hiemcke-Jiwa, Lennart A. Kester, Uta Flucke, Manfred Gessler, Daniel Schrimpf, Felix Sahm, Blaise A. Clarke, Colin J.R. Stewart, Yemin Wang, C. Blake Gilks, Friedrich Kommoss, David G. Huntsman, Ulrich Schüller, Christian Koelsche, W. Glenn McCluggageAndreas von Deimling, William D. Foulkes

Obstetrics and Gynaecology

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16 Citations (Scopus)

Abstract

DICER1 syndrome is a tumor predisposition syndrome that is associated with up to 30 different neoplastic lesions, usually affecting children and adolescents. Here we identify a group of mesenchymal tumors which is highly associated with DICER1 syndrome, and molecularly distinct from other DICER1-associated tumors. This group of DICER1-associated mesenchymal tumors encompasses multiple well-established clinicopathological tumor entities and can be further divided into three clinically meaningful classes designated “low-grade mesenchymal tumor with DICER1 alteration” (LGMT DICER1), “sarcoma with DICER1 alteration” (SARC DICER1), and primary intracranial sarcoma with DICER1 alteration (PIS DICER1). Our study not only provides a combined approach to classify DICER1-associated neoplasms for improved clinical management but also suggests a role for global hypomethylation and other recurrent molecular events in sarcomatous differentiation in mesenchymal tumors with DICER1 alteration. Our results will facilitate future investigations into prognostication and therapeutic approaches for affected patients.

Original language	English
Article number	1677
Journal	Nature Communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-37092-w
Publication status	Published - Dec 2023

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Kommoss, F. K. F., Chong, A. S., Chong, A. L., Pfaff, E., Jones, D. T. W., Hiemcke-Jiwa, L. S., Kester, L. A., Flucke, U., Gessler, M., Schrimpf, D., Sahm, F., Clarke, B. A., Stewart, C. J. R., Wang, Y., Gilks, C. B., Kommoss, F., Huntsman, D. G., Schüller, U., Koelsche, C., ... Foulkes, W. D. (2023). Genomic characterization of DICER1-associated neoplasms uncovers molecular classes. Nature Communications, 14(1), Article 1677. https://doi.org/10.1038/s41467-023-37092-w

@article{4911a3162a3045e089cb90112394028c,

title = "Genomic characterization of DICER1-associated neoplasms uncovers molecular classes",

abstract = "DICER1 syndrome is a tumor predisposition syndrome that is associated with up to 30 different neoplastic lesions, usually affecting children and adolescents. Here we identify a group of mesenchymal tumors which is highly associated with DICER1 syndrome, and molecularly distinct from other DICER1-associated tumors. This group of DICER1-associated mesenchymal tumors encompasses multiple well-established clinicopathological tumor entities and can be further divided into three clinically meaningful classes designated “low-grade mesenchymal tumor with DICER1 alteration” (LGMT DICER1), “sarcoma with DICER1 alteration” (SARC DICER1), and primary intracranial sarcoma with DICER1 alteration (PIS DICER1). Our study not only provides a combined approach to classify DICER1-associated neoplasms for improved clinical management but also suggests a role for global hypomethylation and other recurrent molecular events in sarcomatous differentiation in mesenchymal tumors with DICER1 alteration. Our results will facilitate future investigations into prognostication and therapeutic approaches for affected patients.",

author = "Kommoss, {Felix K.F.} and Chong, {Anne Sophie} and Chong, {Anne Laure} and Elke Pfaff and Jones, {David T.W.} and Hiemcke-Jiwa, {Laura S.} and Kester, {Lennart A.} and Uta Flucke and Manfred Gessler and Daniel Schrimpf and Felix Sahm and Clarke, {Blaise A.} and Stewart, {Colin J.R.} and Yemin Wang and Gilks, {C. Blake} and Friedrich Kommoss and Huntsman, {David G.} and Ulrich Sch{\"u}ller and Christian Koelsche and {Glenn McCluggage}, W. and {von Deimling}, Andreas and Foulkes, {William D.}",

note = "Funding Information: We want to thank the Microarray Unit of the Genomics and Proteomics Core Facility, German Cancer Research Center (DKFZ) for providing excellent technical support. FKFK is supported by the Physician Scientist-Program of Heidelberg University, Germany. A.S.C. is supported by a fellowship (LCF/BQ/DI21/11860051) from “la Caixa” Foundation (ID 1000010434). A.v.D. is supported by an Illumina research grant. W.D.F. is funded by the Canadian Institutes of Health Research (FDN-148390). Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = dec,

doi = "10.1038/s41467-023-37092-w",

language = "English",

volume = "14",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group - Macmillan Publishers",

number = "1",

}

Kommoss, FKF, Chong, AS, Chong, AL, Pfaff, E, Jones, DTW, Hiemcke-Jiwa, LS, Kester, LA, Flucke, U, Gessler, M, Schrimpf, D, Sahm, F, Clarke, BA, Stewart, CJR, Wang, Y, Gilks, CB, Kommoss, F, Huntsman, DG, Schüller, U, Koelsche, C, Glenn McCluggage, W, von Deimling, A & Foulkes, WD 2023, 'Genomic characterization of DICER1-associated neoplasms uncovers molecular classes', Nature Communications, vol. 14, no. 1, 1677. https://doi.org/10.1038/s41467-023-37092-w

TY - JOUR

T1 - Genomic characterization of DICER1-associated neoplasms uncovers molecular classes

AU - Kommoss, Felix K.F.

AU - Chong, Anne Sophie

AU - Chong, Anne Laure

AU - Pfaff, Elke

AU - Jones, David T.W.

AU - Hiemcke-Jiwa, Laura S.

AU - Kester, Lennart A.

AU - Flucke, Uta

AU - Gessler, Manfred

AU - Schrimpf, Daniel

AU - Sahm, Felix

AU - Clarke, Blaise A.

AU - Stewart, Colin J.R.

AU - Wang, Yemin

AU - Gilks, C. Blake

AU - Kommoss, Friedrich

AU - Huntsman, David G.

AU - Schüller, Ulrich

AU - Koelsche, Christian

AU - Glenn McCluggage, W.

AU - von Deimling, Andreas

AU - Foulkes, William D.

N1 - Funding Information: We want to thank the Microarray Unit of the Genomics and Proteomics Core Facility, German Cancer Research Center (DKFZ) for providing excellent technical support. FKFK is supported by the Physician Scientist-Program of Heidelberg University, Germany. A.S.C. is supported by a fellowship (LCF/BQ/DI21/11860051) from “la Caixa” Foundation (ID 1000010434). A.v.D. is supported by an Illumina research grant. W.D.F. is funded by the Canadian Institutes of Health Research (FDN-148390). Publisher Copyright: © 2023, The Author(s).

PY - 2023/12

Y1 - 2023/12

N2 - DICER1 syndrome is a tumor predisposition syndrome that is associated with up to 30 different neoplastic lesions, usually affecting children and adolescents. Here we identify a group of mesenchymal tumors which is highly associated with DICER1 syndrome, and molecularly distinct from other DICER1-associated tumors. This group of DICER1-associated mesenchymal tumors encompasses multiple well-established clinicopathological tumor entities and can be further divided into three clinically meaningful classes designated “low-grade mesenchymal tumor with DICER1 alteration” (LGMT DICER1), “sarcoma with DICER1 alteration” (SARC DICER1), and primary intracranial sarcoma with DICER1 alteration (PIS DICER1). Our study not only provides a combined approach to classify DICER1-associated neoplasms for improved clinical management but also suggests a role for global hypomethylation and other recurrent molecular events in sarcomatous differentiation in mesenchymal tumors with DICER1 alteration. Our results will facilitate future investigations into prognostication and therapeutic approaches for affected patients.

AB - DICER1 syndrome is a tumor predisposition syndrome that is associated with up to 30 different neoplastic lesions, usually affecting children and adolescents. Here we identify a group of mesenchymal tumors which is highly associated with DICER1 syndrome, and molecularly distinct from other DICER1-associated tumors. This group of DICER1-associated mesenchymal tumors encompasses multiple well-established clinicopathological tumor entities and can be further divided into three clinically meaningful classes designated “low-grade mesenchymal tumor with DICER1 alteration” (LGMT DICER1), “sarcoma with DICER1 alteration” (SARC DICER1), and primary intracranial sarcoma with DICER1 alteration (PIS DICER1). Our study not only provides a combined approach to classify DICER1-associated neoplasms for improved clinical management but also suggests a role for global hypomethylation and other recurrent molecular events in sarcomatous differentiation in mesenchymal tumors with DICER1 alteration. Our results will facilitate future investigations into prognostication and therapeutic approaches for affected patients.

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U2 - 10.1038/s41467-023-37092-w

DO - 10.1038/s41467-023-37092-w

M3 - Article

C2 - 36966138

AN - SCOPUS:85150957109

SN - 2041-1723

VL - 14

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 1677

ER -

Genomic characterization of DICER1-associated neoplasms uncovers molecular classes

Abstract

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