POU2AF3-rearranged sarcomas: A novel tumor defined by fusions of EWSR1 or FUS to a gene formerly designated COLCA2

Matthew C. Hiemenz; Jaspreet Kaur; Zheng Kuang; Richard S.P. Huang; Lukas Harries; Dana Metzger; Kelsie Schiavone; Sherri Z. Millis; Douglas I. Lin; Mirna Lechpammer; Brennan Decker; Douglas A. Mata; Abhinav Reddy; Matthew Parke; Eun Y. Lee; Xiaoyan Cui; O. Hans Iwenofu; Darya Buehler; Les Henderson; Erin M. Baldwin; Sosipatros A. Boikos; Shakti H. Ramkissoon; Steven C. Smith

doi:10.1002/gcc.23136

POU2AF3-rearranged sarcomas: A novel tumor defined by fusions of EWSR1 or FUS to a gene formerly designated COLCA2

Matthew C. Hiemenz, Jaspreet Kaur, Zheng Kuang, Richard S.P. Huang, Lukas Harries, Dana Metzger, Kelsie Schiavone, Sherri Z. Millis, Douglas I. Lin, Mirna Lechpammer, Brennan Decker, Douglas A. Mata, Abhinav Reddy, Matthew Parke, Eun Y. Lee, Xiaoyan Cui, O. Hans Iwenofu, Darya Buehler, Les Henderson, Erin M. BaldwinSosipatros A. Boikos, Shakti H. Ramkissoon, Steven C. Smith

Research output: Contribution to journal › Article › peer-review

Abstract

Gene fusions involving EWSR1 or FUS as the 5′ partner have been reported in a diverse array of sarcomas. Here, we characterize the histopathology and genomics of six tumors harboring a gene fusion between EWSR1 or FUS and POU2AF3, an understudied, putative colorectal cancer predisposition gene. Striking morphologic features reminiscent of synovial sarcoma were observed including a biphasic appearance with variable fusiform to epithelioid cytomorphology and staghorn-type vasculature. RNA sequencing demonstrated variable breakpoints in EWSR1/FUS along with similar breakpoints in POU2AF3 that encompassed a 3′ portion of this gene. For cases in which additional information was available, the behavior of these neoplasms was aggressive with local spread and/or distant metastases. Although further studies are needed to confirm the functional significance of our findings, POU2AF3 fusions to EWSR1 or FUS may define a novel type of POU2AF3-rearranged sarcomas with aggressive, malignant behavior.

Original language	English
Pages (from-to)	460-470
Number of pages	11
Journal	Genes Chromosomes and Cancer
Volume	62
Issue number	8
DOIs	https://doi.org/10.1002/gcc.23136
State	Published - Aug 2023

Bibliographical note

Publisher Copyright:
© 2023 Wiley Periodicals LLC.

Keywords

COLCA2
EWSR1
POU2AF3
comprehensive genomic profiling
round-cell sarcoma
synovial sarcoma

ASJC Scopus subject areas

Genetics
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/gcc.23136

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Hiemenz, M. C., Kaur, J., Kuang, Z., Huang, R. S. P., Harries, L., Metzger, D., Schiavone, K., Millis, S. Z., Lin, D. I., Lechpammer, M., Decker, B., Mata, D. A., Reddy, A., Parke, M., Lee, E. Y., Cui, X., Iwenofu, O. H., Buehler, D., Henderson, L., ... Smith, S. C. (2023). POU2AF3-rearranged sarcomas: A novel tumor defined by fusions of EWSR1 or FUS to a gene formerly designated COLCA2. Genes Chromosomes and Cancer, 62(8), 460-470. https://doi.org/10.1002/gcc.23136

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title = "POU2AF3-rearranged sarcomas: A novel tumor defined by fusions of EWSR1 or FUS to a gene formerly designated COLCA2",

abstract = "Gene fusions involving EWSR1 or FUS as the 5′ partner have been reported in a diverse array of sarcomas. Here, we characterize the histopathology and genomics of six tumors harboring a gene fusion between EWSR1 or FUS and POU2AF3, an understudied, putative colorectal cancer predisposition gene. Striking morphologic features reminiscent of synovial sarcoma were observed including a biphasic appearance with variable fusiform to epithelioid cytomorphology and staghorn-type vasculature. RNA sequencing demonstrated variable breakpoints in EWSR1/FUS along with similar breakpoints in POU2AF3 that encompassed a 3′ portion of this gene. For cases in which additional information was available, the behavior of these neoplasms was aggressive with local spread and/or distant metastases. Although further studies are needed to confirm the functional significance of our findings, POU2AF3 fusions to EWSR1 or FUS may define a novel type of POU2AF3-rearranged sarcomas with aggressive, malignant behavior.",

keywords = "COLCA2, EWSR1, POU2AF3, comprehensive genomic profiling, round-cell sarcoma, synovial sarcoma",

author = "Hiemenz, {Matthew C.} and Jaspreet Kaur and Zheng Kuang and Huang, {Richard S.P.} and Lukas Harries and Dana Metzger and Kelsie Schiavone and Millis, {Sherri Z.} and Lin, {Douglas I.} and Mirna Lechpammer and Brennan Decker and Mata, {Douglas A.} and Abhinav Reddy and Matthew Parke and Lee, {Eun Y.} and Xiaoyan Cui and Iwenofu, {O. Hans} and Darya Buehler and Les Henderson and Baldwin, {Erin M.} and Boikos, {Sosipatros A.} and Ramkissoon, {Shakti H.} and Smith, {Steven C.}",

note = "Publisher Copyright: {\textcopyright} 2023 Wiley Periodicals LLC.",

year = "2023",

month = aug,

doi = "10.1002/gcc.23136",

language = "English",

volume = "62",

pages = "460--470",

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Hiemenz, MC, Kaur, J, Kuang, Z, Huang, RSP, Harries, L, Metzger, D, Schiavone, K, Millis, SZ, Lin, DI, Lechpammer, M, Decker, B, Mata, DA, Reddy, A, Parke, M, Lee, EY, Cui, X, Iwenofu, OH, Buehler, D, Henderson, L, Baldwin, EM, Boikos, SA, Ramkissoon, SH & Smith, SC 2023, 'POU2AF3-rearranged sarcomas: A novel tumor defined by fusions of EWSR1 or FUS to a gene formerly designated COLCA2', Genes Chromosomes and Cancer, vol. 62, no. 8, pp. 460-470. https://doi.org/10.1002/gcc.23136

TY - JOUR

T1 - POU2AF3-rearranged sarcomas

T2 - A novel tumor defined by fusions of EWSR1 or FUS to a gene formerly designated COLCA2

AU - Hiemenz, Matthew C.

AU - Kaur, Jaspreet

AU - Kuang, Zheng

AU - Huang, Richard S.P.

AU - Harries, Lukas

AU - Metzger, Dana

AU - Schiavone, Kelsie

AU - Millis, Sherri Z.

AU - Lin, Douglas I.

AU - Lechpammer, Mirna

AU - Decker, Brennan

AU - Mata, Douglas A.

AU - Reddy, Abhinav

AU - Parke, Matthew

AU - Lee, Eun Y.

AU - Cui, Xiaoyan

AU - Iwenofu, O. Hans

AU - Buehler, Darya

AU - Henderson, Les

AU - Baldwin, Erin M.

AU - Boikos, Sosipatros A.

AU - Ramkissoon, Shakti H.

AU - Smith, Steven C.

PY - 2023/8

Y1 - 2023/8

N2 - Gene fusions involving EWSR1 or FUS as the 5′ partner have been reported in a diverse array of sarcomas. Here, we characterize the histopathology and genomics of six tumors harboring a gene fusion between EWSR1 or FUS and POU2AF3, an understudied, putative colorectal cancer predisposition gene. Striking morphologic features reminiscent of synovial sarcoma were observed including a biphasic appearance with variable fusiform to epithelioid cytomorphology and staghorn-type vasculature. RNA sequencing demonstrated variable breakpoints in EWSR1/FUS along with similar breakpoints in POU2AF3 that encompassed a 3′ portion of this gene. For cases in which additional information was available, the behavior of these neoplasms was aggressive with local spread and/or distant metastases. Although further studies are needed to confirm the functional significance of our findings, POU2AF3 fusions to EWSR1 or FUS may define a novel type of POU2AF3-rearranged sarcomas with aggressive, malignant behavior.

AB - Gene fusions involving EWSR1 or FUS as the 5′ partner have been reported in a diverse array of sarcomas. Here, we characterize the histopathology and genomics of six tumors harboring a gene fusion between EWSR1 or FUS and POU2AF3, an understudied, putative colorectal cancer predisposition gene. Striking morphologic features reminiscent of synovial sarcoma were observed including a biphasic appearance with variable fusiform to epithelioid cytomorphology and staghorn-type vasculature. RNA sequencing demonstrated variable breakpoints in EWSR1/FUS along with similar breakpoints in POU2AF3 that encompassed a 3′ portion of this gene. For cases in which additional information was available, the behavior of these neoplasms was aggressive with local spread and/or distant metastases. Although further studies are needed to confirm the functional significance of our findings, POU2AF3 fusions to EWSR1 or FUS may define a novel type of POU2AF3-rearranged sarcomas with aggressive, malignant behavior.

KW - COLCA2

KW - EWSR1

KW - POU2AF3

KW - comprehensive genomic profiling

KW - round-cell sarcoma

KW - synovial sarcoma

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UR - http://www.scopus.com/inward/citedby.url?scp=85152076709&partnerID=8YFLogxK

U2 - 10.1002/gcc.23136

DO - 10.1002/gcc.23136

M3 - Article

C2 - 36862145

AN - SCOPUS:85152076709

SN - 1045-2257

VL - 62

SP - 460

EP - 470

JO - Genes Chromosomes and Cancer

JF - Genes Chromosomes and Cancer

IS - 8

ER -

POU2AF3-rearranged sarcomas: A novel tumor defined by fusions of EWSR1 or FUS to a gene formerly designated COLCA2

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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