Characterization of the chromosomal translocation t(10;17)(q22;p13) in clear cell sarcoma of kidney

Elaine O'Meara, Deirdre Stack, Cheng Han Lee, A. Julian Garvin, Thomas Morris, Pedram Argani, Jeong S. Han, Jenny Karlsson, David Gisselson, Ivo Leuschner, Manfred Gessler, Norbert Graf, Jonathan A. Fletcher, Maureen J. O'Sullivan

Research output: Contribution to journalArticle

Abstract

Clear cell sarcoma of kidney (CCSK) is classified as a tumour of unfavourable histology by the National Wilms'Tumor Study Group. It has worse clinical outcomes than Wilms' tumour. Virtually nothing is known about CCSK biology, as there have been very few genetic aberrations identified to act as pointers in this cancer. Three cases of CCSK bearing a chromosomal translocation, t(10;17)(q22;p13), have been individually reported but not further investigated to date. The aim of this research was to characterize t(10;17)(q22;p13) in CCSK to identify the genes involved in the translocation breakpoints. Using fluorescently labelled bacterial artificial chromosomes (BACs) and a chromosome-walking strategy on an index case of CCSK with t(10;17)(q22;p13) by karyotype, we identified the chromosomal breakpoints on 17p13.3 and 10q22.3. The translocation results in rearrangement of YWHAE on chromosome 17 and FAM22 on chromosome 10, producing an in-frame fusion transcript of ∼3 kb, incorporating exons 1-5 of YWHAE and exons 2-7 of FAM22, as determined by RT-PCR using YWHAE- and FAM22-specific primers. The YWHAE-FAM22 transcript was detected in six of 50 further CCSKs tested, therefore showing an overall incidence of 12% in our cohort. No transcript-positive cases presented with stage I disease, despite this being the stage for 31% of our cohort. Tumour cellularity was significantly higher in the cases that were transcript-positive. Based on the chromosome 10 breakpoint identified by FISH and the sequences of the full-length transcripts obtained, the FAM22 members involved in the translocation in these CCSK cases include FAM22B and FAM22E. Elucidation of the role of YWHAE-FAM22 in CCSK will assist development of more efficient and targeted therapies for this childhood cancer, which currently has poor outcomes.

Original languageEnglish (US)
Pages (from-to)72-80
Number of pages9
JournalJournal of Pathology
Volume227
Issue number1
DOIs
StatePublished - May 2012

Fingerprint

Clear Cell Sarcoma
Genetic Translocation
Kidney
Chromosomes, Human, Pair 10
Wilms Tumor
Exons
Neoplasms
Chromosome Walking
Chromosome Breakpoints
Bacterial Artificial Chromosomes
Chromosomes, Human, Pair 17
Karyotype
Histology
Polymerase Chain Reaction
Incidence

Keywords

  • Childhood
  • Chromosomal translocation
  • Clear cell sarcoma of kidney
  • FAM22
  • YWHAE

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

O'Meara, E., Stack, D., Lee, C. H., Garvin, A. J., Morris, T., Argani, P., ... O'Sullivan, M. J. (2012). Characterization of the chromosomal translocation t(10;17)(q22;p13) in clear cell sarcoma of kidney. Journal of Pathology, 227(1), 72-80. https://doi.org/10.1002/path.3985

Characterization of the chromosomal translocation t(10;17)(q22;p13) in clear cell sarcoma of kidney. / O'Meara, Elaine; Stack, Deirdre; Lee, Cheng Han; Garvin, A. Julian; Morris, Thomas; Argani, Pedram; Han, Jeong S.; Karlsson, Jenny; Gisselson, David; Leuschner, Ivo; Gessler, Manfred; Graf, Norbert; Fletcher, Jonathan A.; O'Sullivan, Maureen J.

In: Journal of Pathology, Vol. 227, No. 1, 05.2012, p. 72-80.

Research output: Contribution to journalArticle

O'Meara, E, Stack, D, Lee, CH, Garvin, AJ, Morris, T, Argani, P, Han, JS, Karlsson, J, Gisselson, D, Leuschner, I, Gessler, M, Graf, N, Fletcher, JA & O'Sullivan, MJ 2012, 'Characterization of the chromosomal translocation t(10;17)(q22;p13) in clear cell sarcoma of kidney', Journal of Pathology, vol. 227, no. 1, pp. 72-80. https://doi.org/10.1002/path.3985
O'Meara, Elaine ; Stack, Deirdre ; Lee, Cheng Han ; Garvin, A. Julian ; Morris, Thomas ; Argani, Pedram ; Han, Jeong S. ; Karlsson, Jenny ; Gisselson, David ; Leuschner, Ivo ; Gessler, Manfred ; Graf, Norbert ; Fletcher, Jonathan A. ; O'Sullivan, Maureen J. / Characterization of the chromosomal translocation t(10;17)(q22;p13) in clear cell sarcoma of kidney. In: Journal of Pathology. 2012 ; Vol. 227, No. 1. pp. 72-80.
@article{788f759b526c4cfdbe8c69bb5b508e1d,
title = "Characterization of the chromosomal translocation t(10;17)(q22;p13) in clear cell sarcoma of kidney",
abstract = "Clear cell sarcoma of kidney (CCSK) is classified as a tumour of unfavourable histology by the National Wilms'Tumor Study Group. It has worse clinical outcomes than Wilms' tumour. Virtually nothing is known about CCSK biology, as there have been very few genetic aberrations identified to act as pointers in this cancer. Three cases of CCSK bearing a chromosomal translocation, t(10;17)(q22;p13), have been individually reported but not further investigated to date. The aim of this research was to characterize t(10;17)(q22;p13) in CCSK to identify the genes involved in the translocation breakpoints. Using fluorescently labelled bacterial artificial chromosomes (BACs) and a chromosome-walking strategy on an index case of CCSK with t(10;17)(q22;p13) by karyotype, we identified the chromosomal breakpoints on 17p13.3 and 10q22.3. The translocation results in rearrangement of YWHAE on chromosome 17 and FAM22 on chromosome 10, producing an in-frame fusion transcript of ∼3 kb, incorporating exons 1-5 of YWHAE and exons 2-7 of FAM22, as determined by RT-PCR using YWHAE- and FAM22-specific primers. The YWHAE-FAM22 transcript was detected in six of 50 further CCSKs tested, therefore showing an overall incidence of 12{\%} in our cohort. No transcript-positive cases presented with stage I disease, despite this being the stage for 31{\%} of our cohort. Tumour cellularity was significantly higher in the cases that were transcript-positive. Based on the chromosome 10 breakpoint identified by FISH and the sequences of the full-length transcripts obtained, the FAM22 members involved in the translocation in these CCSK cases include FAM22B and FAM22E. Elucidation of the role of YWHAE-FAM22 in CCSK will assist development of more efficient and targeted therapies for this childhood cancer, which currently has poor outcomes.",
keywords = "Childhood, Chromosomal translocation, Clear cell sarcoma of kidney, FAM22, YWHAE",
author = "Elaine O'Meara and Deirdre Stack and Lee, {Cheng Han} and Garvin, {A. Julian} and Thomas Morris and Pedram Argani and Han, {Jeong S.} and Jenny Karlsson and David Gisselson and Ivo Leuschner and Manfred Gessler and Norbert Graf and Fletcher, {Jonathan A.} and O'Sullivan, {Maureen J.}",
year = "2012",
month = "5",
doi = "10.1002/path.3985",
language = "English (US)",
volume = "227",
pages = "72--80",
journal = "Journal of Pathology",
issn = "0022-3417",
publisher = "John Wiley and Sons Ltd",
number = "1",

}

TY - JOUR

T1 - Characterization of the chromosomal translocation t(10;17)(q22;p13) in clear cell sarcoma of kidney

AU - O'Meara, Elaine

AU - Stack, Deirdre

AU - Lee, Cheng Han

AU - Garvin, A. Julian

AU - Morris, Thomas

AU - Argani, Pedram

AU - Han, Jeong S.

AU - Karlsson, Jenny

AU - Gisselson, David

AU - Leuschner, Ivo

AU - Gessler, Manfred

AU - Graf, Norbert

AU - Fletcher, Jonathan A.

AU - O'Sullivan, Maureen J.

PY - 2012/5

Y1 - 2012/5

N2 - Clear cell sarcoma of kidney (CCSK) is classified as a tumour of unfavourable histology by the National Wilms'Tumor Study Group. It has worse clinical outcomes than Wilms' tumour. Virtually nothing is known about CCSK biology, as there have been very few genetic aberrations identified to act as pointers in this cancer. Three cases of CCSK bearing a chromosomal translocation, t(10;17)(q22;p13), have been individually reported but not further investigated to date. The aim of this research was to characterize t(10;17)(q22;p13) in CCSK to identify the genes involved in the translocation breakpoints. Using fluorescently labelled bacterial artificial chromosomes (BACs) and a chromosome-walking strategy on an index case of CCSK with t(10;17)(q22;p13) by karyotype, we identified the chromosomal breakpoints on 17p13.3 and 10q22.3. The translocation results in rearrangement of YWHAE on chromosome 17 and FAM22 on chromosome 10, producing an in-frame fusion transcript of ∼3 kb, incorporating exons 1-5 of YWHAE and exons 2-7 of FAM22, as determined by RT-PCR using YWHAE- and FAM22-specific primers. The YWHAE-FAM22 transcript was detected in six of 50 further CCSKs tested, therefore showing an overall incidence of 12% in our cohort. No transcript-positive cases presented with stage I disease, despite this being the stage for 31% of our cohort. Tumour cellularity was significantly higher in the cases that were transcript-positive. Based on the chromosome 10 breakpoint identified by FISH and the sequences of the full-length transcripts obtained, the FAM22 members involved in the translocation in these CCSK cases include FAM22B and FAM22E. Elucidation of the role of YWHAE-FAM22 in CCSK will assist development of more efficient and targeted therapies for this childhood cancer, which currently has poor outcomes.

AB - Clear cell sarcoma of kidney (CCSK) is classified as a tumour of unfavourable histology by the National Wilms'Tumor Study Group. It has worse clinical outcomes than Wilms' tumour. Virtually nothing is known about CCSK biology, as there have been very few genetic aberrations identified to act as pointers in this cancer. Three cases of CCSK bearing a chromosomal translocation, t(10;17)(q22;p13), have been individually reported but not further investigated to date. The aim of this research was to characterize t(10;17)(q22;p13) in CCSK to identify the genes involved in the translocation breakpoints. Using fluorescently labelled bacterial artificial chromosomes (BACs) and a chromosome-walking strategy on an index case of CCSK with t(10;17)(q22;p13) by karyotype, we identified the chromosomal breakpoints on 17p13.3 and 10q22.3. The translocation results in rearrangement of YWHAE on chromosome 17 and FAM22 on chromosome 10, producing an in-frame fusion transcript of ∼3 kb, incorporating exons 1-5 of YWHAE and exons 2-7 of FAM22, as determined by RT-PCR using YWHAE- and FAM22-specific primers. The YWHAE-FAM22 transcript was detected in six of 50 further CCSKs tested, therefore showing an overall incidence of 12% in our cohort. No transcript-positive cases presented with stage I disease, despite this being the stage for 31% of our cohort. Tumour cellularity was significantly higher in the cases that were transcript-positive. Based on the chromosome 10 breakpoint identified by FISH and the sequences of the full-length transcripts obtained, the FAM22 members involved in the translocation in these CCSK cases include FAM22B and FAM22E. Elucidation of the role of YWHAE-FAM22 in CCSK will assist development of more efficient and targeted therapies for this childhood cancer, which currently has poor outcomes.

KW - Childhood

KW - Chromosomal translocation

KW - Clear cell sarcoma of kidney

KW - FAM22

KW - YWHAE

UR - http://www.scopus.com/inward/record.url?scp=84862777245&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862777245&partnerID=8YFLogxK

U2 - 10.1002/path.3985

DO - 10.1002/path.3985

M3 - Article

C2 - 22294382

AN - SCOPUS:84862777245

VL - 227

SP - 72

EP - 80

JO - Journal of Pathology

JF - Journal of Pathology

SN - 0022-3417

IS - 1

ER -