EWS rearrangement in Ewing's sarcoma and peripheral neuroectodermal tumor molecular detection and correlation with cytogenetic analysis and MIC2 expression Journal Article

  

Authors:	Ladanyi, M.; Lewis, R.; Garin-Chesa, P.; Rettig, W. J.; Huvos, A. G.; Healey, J. H.; Jhanwar, S. C.
Article Title:	EWS rearrangement in Ewing's sarcoma and peripheral neuroectodermal tumor molecular detection and correlation with cytogenetic analysis and MIC2 expression
Abstract:	The translocation t(l 1;22)(q24;ql2) can be identified in its classical or variant form in approximately 90% of cases of Ewing's sarcoma (ES) and peripheral neuroectodermal tumor (PNET). In this tumor group in which the histopathologic diagnosis is often one of exclusion, the cytogenetic demonstration of this translocation has become an invaluable positive diagnostic marker. With the recent cloning of the breakpoint regions of the t(ll;22), molecular genetic approaches to the detection of this translocation have become possible. By Southern blotting, the position of the breakpoints on chromosome 22 has been found to be tightly clustered within a 7-kilobase (kb) fragment of the genomic DNA, within a gene designated EWS. In the present study, we examined the efficacy of an EWS complementary DNA (cDNA) probe in detecting the t(ll;22) in Southern blots of EcoRl- or Hindlll-digested DNA extracted from cases of ES and PNET. We also compared the results of the molecular and cytogenetic analysis with the expression of the ES cell surface antigen MIC2, as demonstrated by immunoperoxidase staining with the monoclonal antibodies 013 and HBA71. Twenty-three specimens were studied, including 18 ES and five PNET. Of 16 cases with clonally abnormal karyotypes, 14 (88%) showed a typical or variant t(ll;22). Rearrangements were demonstrated within the EWS gene with the EWS cDNA probe in 20 of 23 specimens (87%), including all of the 14 cases, as well as in one case that displayed clonal numerical chromosome abnormalities only. The MIC2 antigen was expressed in 19 of 20 cases 95%, including all three cases lacking EWS re-arrangement.The sole case that did not express MIC2 did, however, display a variant t(ll;22) and EWS rearrangement; hence, our findings illustrate the importance of combining diagnostic modalities in the complete evaluation of this group of tumors. Furthermore, Southern blot detection of EWS rearrangement appears to be a highly reliable test for the presence of the t(11;22) and is likely to be as specific for the diagnosis of ES or PNET as the translocation itself. The availability of molecular probes for this translocation should widen its diagnostic application. © 1993 Raven-press. Ltd.
Keywords:	adolescent; adult; child; clinical article; human tissue; child, preschool; human cell; molecular genetics; antigen expression; tumor cells, cultured; tumor antigen; ewing sarcoma; membrane antigen; gene rearrangement; molecular sequence data; membrane glycoproteins; dna, neoplasm; chromosome breakage; chromosome translocation; base sequence; cell adhesion molecules; evaluation studies; sarcoma, ewing's; chromosome analysis; chromosomes, human, pair 11; neuroectoderm tumor; neuroectodermal tumors, primitive, peripheral; chromosomes, human, pair 22; translocation; southern blotting; molecular diagnosis; ewing's sarcoma; rearrangement; dna probes; blotting, southern; peripheral neuroectodermal tumor; ews gene; human; male; female; article; support, non-u.s. gov't; dna probe; translocation (genetics); 1(11; 22)(q24; mic2 antigen; q 12)
Journal Title:	Diagnostic Molecular Pathology
Volume:	2
Issue:	3
ISSN:	1052-9551
Publisher:	Lippincott Williams & Wilkins
Date Published:	1993-09-01
Start Page:	141
End Page:	146
Language:	English
PUBMED:	8287228
PROVIDER:	scopus
DOI:	10.1097/00019606-199309000-00001
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0027258038&partnerID=40&md5=e9b024ec74f6ae1268703e092e9aa25d
Notes:	Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/143939