Genomic gains and losses are similar in genetic and histologic subsets of rhabdomyosarcoma, whereas amplification predominates in embryonal with anaplasia and alveolar subtypes

Julia A. Bridge, Jian Liu, Stephen J. Qualman, Ron Suijkerbuijk, Gail Wenger, Ji Zhang, Xiaoying Wan, K. Scott Baker, Poul Sorensen, Frederic G. Barr

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

In this investigation, we selected PAX3/FKHR and PAX7/FKHR fusion transcript-positive and -negative alveolar rhabdomyosarcomas (ARMSs) and embryonal rhabdomyosarcomas (ERMSs) with and without anaplastic features, to ascertain genomic imbalance differences and/or similarities within these histopathologic and genetic rhabdomyosarcoma (RMS) variants. Comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) studies were performed on 45 rhabdomyosarcoma specimens consisting of 23 ARMSs and 22 ERMSs (12 ERMS cases were included from an earlier study). The anaplastic variant of RMS has not previously been subjected to CGH analysis. Overall, the most prominent imbalances were gain of chromosomes or chromosomal regions 2/2q (40%), 7/7q (31%), 8/8p (53%), 11/11q (31%), 12q13-15 (49%), 13q14 (22%), and 20/20p (31%), and loss of 1p36 (27%), 3p14-21 (22%), 9q21-22 (33%), 10q22-qter (18%), 16q (27%), 17p (22%), and 22 (22%). These gains and losses were distributed equally between ARMS and ERMS histologic subtypes (excluding 7/7q and 11/11q gain that were observed chiefly in ERMS), demonstrating that these entities are similar with respect to recurrent genomic imbalances. Moreover, genomic imbalances were also evenly distributed among the ARMS fusion transcript subtypes, providing evidence for a genetic kinship despite the absence of a fusion transcript in some cases. Genomic amplification was detected in 26% and 23% of the ARMS and ERMS cases, respectively (with nearly all of the latter subset exhibiting anaplastic features). One amplicon, involving 15q25-26, corresponds to the locus of the insulin-like growth factor type I receptor (IGFIR) gene. Amplification of IGFIR was confirmed molecularly in the cases exhibiting a 15q25-26 amplicon. In summary, these results indicate that genomic gains and losses involve alike chromosomes with similar frequencies within the histopathologic and genetic subtypes of rhabdomyosarcoma, that genomic amplification is frequent not only in the alveolar histologic subtype of rhabdomyosarcoma but also in ERMS with anaplasia, and that amplification of IGFIR possibly plays a role in the development or progression of a subset of rhabdomyosarcomas.

Original languageEnglish (US)
Pages (from-to)310-321
Number of pages12
JournalGenes Chromosomes and Cancer
Volume33
Issue number3
DOIs
StatePublished - Feb 18 2002

Fingerprint

Anaplasia
Embryonal Rhabdomyosarcoma
Rhabdomyosarcoma
Alveolar Rhabdomyosarcoma
IGF Type 1 Receptor
Comparative Genomic Hybridization
Chromosomes
Fluorescence In Situ Hybridization
In Situ Hybridization

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

Cite this

Genomic gains and losses are similar in genetic and histologic subsets of rhabdomyosarcoma, whereas amplification predominates in embryonal with anaplasia and alveolar subtypes. / Bridge, Julia A.; Liu, Jian; Qualman, Stephen J.; Suijkerbuijk, Ron; Wenger, Gail; Zhang, Ji; Wan, Xiaoying; Baker, K. Scott; Sorensen, Poul; Barr, Frederic G.

In: Genes Chromosomes and Cancer, Vol. 33, No. 3, 18.02.2002, p. 310-321.

Research output: Contribution to journalArticle

Bridge, Julia A. ; Liu, Jian ; Qualman, Stephen J. ; Suijkerbuijk, Ron ; Wenger, Gail ; Zhang, Ji ; Wan, Xiaoying ; Baker, K. Scott ; Sorensen, Poul ; Barr, Frederic G. / Genomic gains and losses are similar in genetic and histologic subsets of rhabdomyosarcoma, whereas amplification predominates in embryonal with anaplasia and alveolar subtypes. In: Genes Chromosomes and Cancer. 2002 ; Vol. 33, No. 3. pp. 310-321.
@article{06a53ff561a749fa9609ba0e446a040f,
title = "Genomic gains and losses are similar in genetic and histologic subsets of rhabdomyosarcoma, whereas amplification predominates in embryonal with anaplasia and alveolar subtypes",
abstract = "In this investigation, we selected PAX3/FKHR and PAX7/FKHR fusion transcript-positive and -negative alveolar rhabdomyosarcomas (ARMSs) and embryonal rhabdomyosarcomas (ERMSs) with and without anaplastic features, to ascertain genomic imbalance differences and/or similarities within these histopathologic and genetic rhabdomyosarcoma (RMS) variants. Comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) studies were performed on 45 rhabdomyosarcoma specimens consisting of 23 ARMSs and 22 ERMSs (12 ERMS cases were included from an earlier study). The anaplastic variant of RMS has not previously been subjected to CGH analysis. Overall, the most prominent imbalances were gain of chromosomes or chromosomal regions 2/2q (40{\%}), 7/7q (31{\%}), 8/8p (53{\%}), 11/11q (31{\%}), 12q13-15 (49{\%}), 13q14 (22{\%}), and 20/20p (31{\%}), and loss of 1p36 (27{\%}), 3p14-21 (22{\%}), 9q21-22 (33{\%}), 10q22-qter (18{\%}), 16q (27{\%}), 17p (22{\%}), and 22 (22{\%}). These gains and losses were distributed equally between ARMS and ERMS histologic subtypes (excluding 7/7q and 11/11q gain that were observed chiefly in ERMS), demonstrating that these entities are similar with respect to recurrent genomic imbalances. Moreover, genomic imbalances were also evenly distributed among the ARMS fusion transcript subtypes, providing evidence for a genetic kinship despite the absence of a fusion transcript in some cases. Genomic amplification was detected in 26{\%} and 23{\%} of the ARMS and ERMS cases, respectively (with nearly all of the latter subset exhibiting anaplastic features). One amplicon, involving 15q25-26, corresponds to the locus of the insulin-like growth factor type I receptor (IGFIR) gene. Amplification of IGFIR was confirmed molecularly in the cases exhibiting a 15q25-26 amplicon. In summary, these results indicate that genomic gains and losses involve alike chromosomes with similar frequencies within the histopathologic and genetic subtypes of rhabdomyosarcoma, that genomic amplification is frequent not only in the alveolar histologic subtype of rhabdomyosarcoma but also in ERMS with anaplasia, and that amplification of IGFIR possibly plays a role in the development or progression of a subset of rhabdomyosarcomas.",
author = "Bridge, {Julia A.} and Jian Liu and Qualman, {Stephen J.} and Ron Suijkerbuijk and Gail Wenger and Ji Zhang and Xiaoying Wan and Baker, {K. Scott} and Poul Sorensen and Barr, {Frederic G.}",
year = "2002",
month = "2",
day = "18",
doi = "10.1002/gcc.10026",
language = "English (US)",
volume = "33",
pages = "310--321",
journal = "Genes Chromosomes and Cancer",
issn = "1045-2257",
publisher = "Wiley-Liss Inc.",
number = "3",

}

TY - JOUR

T1 - Genomic gains and losses are similar in genetic and histologic subsets of rhabdomyosarcoma, whereas amplification predominates in embryonal with anaplasia and alveolar subtypes

AU - Bridge, Julia A.

AU - Liu, Jian

AU - Qualman, Stephen J.

AU - Suijkerbuijk, Ron

AU - Wenger, Gail

AU - Zhang, Ji

AU - Wan, Xiaoying

AU - Baker, K. Scott

AU - Sorensen, Poul

AU - Barr, Frederic G.

PY - 2002/2/18

Y1 - 2002/2/18

N2 - In this investigation, we selected PAX3/FKHR and PAX7/FKHR fusion transcript-positive and -negative alveolar rhabdomyosarcomas (ARMSs) and embryonal rhabdomyosarcomas (ERMSs) with and without anaplastic features, to ascertain genomic imbalance differences and/or similarities within these histopathologic and genetic rhabdomyosarcoma (RMS) variants. Comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) studies were performed on 45 rhabdomyosarcoma specimens consisting of 23 ARMSs and 22 ERMSs (12 ERMS cases were included from an earlier study). The anaplastic variant of RMS has not previously been subjected to CGH analysis. Overall, the most prominent imbalances were gain of chromosomes or chromosomal regions 2/2q (40%), 7/7q (31%), 8/8p (53%), 11/11q (31%), 12q13-15 (49%), 13q14 (22%), and 20/20p (31%), and loss of 1p36 (27%), 3p14-21 (22%), 9q21-22 (33%), 10q22-qter (18%), 16q (27%), 17p (22%), and 22 (22%). These gains and losses were distributed equally between ARMS and ERMS histologic subtypes (excluding 7/7q and 11/11q gain that were observed chiefly in ERMS), demonstrating that these entities are similar with respect to recurrent genomic imbalances. Moreover, genomic imbalances were also evenly distributed among the ARMS fusion transcript subtypes, providing evidence for a genetic kinship despite the absence of a fusion transcript in some cases. Genomic amplification was detected in 26% and 23% of the ARMS and ERMS cases, respectively (with nearly all of the latter subset exhibiting anaplastic features). One amplicon, involving 15q25-26, corresponds to the locus of the insulin-like growth factor type I receptor (IGFIR) gene. Amplification of IGFIR was confirmed molecularly in the cases exhibiting a 15q25-26 amplicon. In summary, these results indicate that genomic gains and losses involve alike chromosomes with similar frequencies within the histopathologic and genetic subtypes of rhabdomyosarcoma, that genomic amplification is frequent not only in the alveolar histologic subtype of rhabdomyosarcoma but also in ERMS with anaplasia, and that amplification of IGFIR possibly plays a role in the development or progression of a subset of rhabdomyosarcomas.

AB - In this investigation, we selected PAX3/FKHR and PAX7/FKHR fusion transcript-positive and -negative alveolar rhabdomyosarcomas (ARMSs) and embryonal rhabdomyosarcomas (ERMSs) with and without anaplastic features, to ascertain genomic imbalance differences and/or similarities within these histopathologic and genetic rhabdomyosarcoma (RMS) variants. Comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) studies were performed on 45 rhabdomyosarcoma specimens consisting of 23 ARMSs and 22 ERMSs (12 ERMS cases were included from an earlier study). The anaplastic variant of RMS has not previously been subjected to CGH analysis. Overall, the most prominent imbalances were gain of chromosomes or chromosomal regions 2/2q (40%), 7/7q (31%), 8/8p (53%), 11/11q (31%), 12q13-15 (49%), 13q14 (22%), and 20/20p (31%), and loss of 1p36 (27%), 3p14-21 (22%), 9q21-22 (33%), 10q22-qter (18%), 16q (27%), 17p (22%), and 22 (22%). These gains and losses were distributed equally between ARMS and ERMS histologic subtypes (excluding 7/7q and 11/11q gain that were observed chiefly in ERMS), demonstrating that these entities are similar with respect to recurrent genomic imbalances. Moreover, genomic imbalances were also evenly distributed among the ARMS fusion transcript subtypes, providing evidence for a genetic kinship despite the absence of a fusion transcript in some cases. Genomic amplification was detected in 26% and 23% of the ARMS and ERMS cases, respectively (with nearly all of the latter subset exhibiting anaplastic features). One amplicon, involving 15q25-26, corresponds to the locus of the insulin-like growth factor type I receptor (IGFIR) gene. Amplification of IGFIR was confirmed molecularly in the cases exhibiting a 15q25-26 amplicon. In summary, these results indicate that genomic gains and losses involve alike chromosomes with similar frequencies within the histopathologic and genetic subtypes of rhabdomyosarcoma, that genomic amplification is frequent not only in the alveolar histologic subtype of rhabdomyosarcoma but also in ERMS with anaplasia, and that amplification of IGFIR possibly plays a role in the development or progression of a subset of rhabdomyosarcomas.

UR - http://www.scopus.com/inward/record.url?scp=18244374534&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=18244374534&partnerID=8YFLogxK

U2 - 10.1002/gcc.10026

DO - 10.1002/gcc.10026

M3 - Article

VL - 33

SP - 310

EP - 321

JO - Genes Chromosomes and Cancer

JF - Genes Chromosomes and Cancer

SN - 1045-2257

IS - 3

ER -