Elsevier

Human Pathology

Volume 31, Issue 5, May 2000, Pages 532-538
Human Pathology

Contribution of molecular genetic data to the classification of sarcomas

https://doi.org/10.1053/hp.2000.6706Get rights and content

Abstract

Many sarcomas are characterized by specific recurrent chromosomal translocations which provide powerful diagnostic tumor markers. Since 1992, the genes involved by almost all of these translocations have been cloned, inaugurating a new era in the study of sarcomas. At the biological level, these chromosomal translocations produce highly specific gene fusions, usually encoding aberrant chimeric transcription factors. Clinically, the correlation of these translocationderived genetic markers and discrete histopathologic entities has been remarkable. Fusion gene detection has confirmed and refined the nosology of several sarcoma groups. The overall effect has been to strengthen certain pathological concepts rather than to revolutionize. The focus of this brief review is the recent impact that the cytogenetic and molecular detection of these translocations has had on sarcoma diagnosis and classification.

References (133)

  • SozziG. et al.

    Relevance of cytogenetic and fluorescent in situ hybridization analyses in the clinical assessment of soft tissue sarcoma

    Hum Patrol

    (1997)
  • TsujiS. et al.

    Detection of SYT-SSX fusion transcripts in synovial sarcoma by reverse transcription-polymerase chain reaction using archival paraffin-embeddedtissues

    Am J Pathol

    (1998)
  • ArganiP. et al.

    Detection of the ETV6-NTRK3 chimeric RNA of infantile fibrosarcoma/cellular congenital mesoblastic nephroma in paraffin-embedded tissue: Application to challenging pediatric renal stromal tumors

    Mod Pathol

    (2000)
  • ShiotaM. et al.

    Diagnosis of t(2;5) (p23;g35)-associated ki-1 lymphoma with immunohistochemistry

    Blood

    (1994)
  • PulfordK. et al.

    Detection of anaplastic lymphoma kinase (ALK) and nucleolar protein nucleophosmin (NPM)-ALK proteins in normal and neoplastic cells with the monoclonal antibody ALKI

    Blood

    (1997)
  • RubinB.P. et al.

    Congenital mesoblastic nephroma t(12;15) Is associated with ETV6-N7RK3 gene fusion: Cytogenetic and molecular relationship to congenital (infantile) fibrosarcoma

    Am J Pathol

    (1998)
  • LasotaJ. et al.

    Mutations in exon 11 of c-Kit occur preferentially in malignant versus benign gastrointestinal stromal tumors and do not occur in leiomyomas orleiomyosarcomas

    Am J Pathol

    (1999)
  • PetitM.M. et al.

    Expression of reciprocal fusion transcripts of the HMGIC and LPP genes in parosteal lipoma

    Cancer Genet Cytogenet

    (1998)
  • WolfA.N. et al.

    The expanding clinical spectrum of desmoplastic small round-cell tumor: A report of two cases with molecular confirmation

    Hum Pathol.

    (1999)
  • BarrF.G. et al.

    Molecular assays for chromosomal translocations in the diagnosis of pediatric soft tissue sarcomas

    JAMA

    (1995)
  • de AlavaE. et al.

    Detection of chimeric transcripts in desmoplastic small round cell tumor and related developmental tumors by reverse transcriptase polymerase chainreaction: A specific diagnostic assay

    Am J Pathol

    (1995)
  • Dockhorn-DworniczakB. et al.

    Assessment of molecular genetic detection of chromosome translocations in the differential diagnosis of pediatric sarcomas

    Klin Padiatr

    (1997)
  • KnezevichS.R. et al.

    A novel ETV6-NTRK3 gene fusion in congenital fibrosarcoma

    Nat Genet

    (1998)
  • SimonM.P. et al.

    Deregulation of the platelet-derived growth factor B-chain gene via fusion with collagen gene COLIA1 in dermatofibrosarcoma protuberans andgiant-cell fibroblastoma

    Nat Genet

    (1997)
  • HirotaS. et al.

    Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors

    Science

    (1998)
  • VersteegeI. et al.

    Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer

    Nature

    (1998)
  • BarrF.G.

    Translocations, cancer and the puzzle of specificity

    Nat Genet

    (1998)
  • RabbittsT.H.

    Chromosomal translocations can affect genes controlling gene expression and differentiation: Why are these functions targeted?

    J Pathol

    (1999)
  • DelattreO. et al.

    Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours

    Nature

    (1992)
  • SorensenP.H.B. et al.

    A second Ewing's sarcoma translocation, t(21;22), fuses the EWS gene to another ets-family transcription factor, ERG

    Nat Genet

    (1994)
  • ZucmanJ. et al.

    Combinatorial generation of variable fusion proteins in the Ewing family of tumours

    EMBO J

    (1993)
  • JeonI.S. et al.

    A variant Ewing's sarcoma translocation (7;22) fuses the EWS gene to the ETS gene ETVI

    Oncogene

    (1995)
  • KanekoY. et al.

    Fusion of an ETS-family gene, EIAF to EWS by[(17;22) (g12;q12) chromosome translocation in an undifferentiated sarcoma of infancy

    Genes Chromosom Cancer

    (1996)
  • PeterM. et al.

    A new member of the ETS family fused to EWS in Ewing tumors

    Oncogene

    (1997)
  • LadanyiM. et al.

    Fusion of the EWS and WTI genes in the desmoplastic small round cell tumor

    Cancer Res

    (1994)
  • CrozatA. et al.

    Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma

    Nature

    (1993)
  • RabbittsT.H. et al.

    Fusion of the dominant negative transcription regulator CHOP with a novel gene FUS by translocation [(12;16) in malignant liposarcoma

    Nat Genet

    (1993)
  • PanagopoulosI. et al.

    Fusion of the EWS and CHOP genes in myxoid liposarcoma

    Oncogene

    (1996)
  • LabelleY. et al.

    Oncogenic conversion of a novel orphan nuclear receptor by chromosome translocation

    Hum Mot Genet

    (1995)
  • ClarkJ. et al.

    Fusion of EWS gene to CHN, a member of the steroid/thyroid receptor gene superfamily, in a human myxoid chondrosarcoma

    Oncogene

    (1996)
  • SjogrenH. et al.

    Fusion of the EWS-related gene TAF2N to TEC in extra skeletal myxoid chondrosarcoma

    Cancer Res

    (1999)
  • PanagopoulosI. et al.

    Fusion of the RBP56 and CHN genes in extraskeletal myxoid chondrosarcomas with translocation [(9;17) (g22;q11)

    Oncogene

    (1999)
  • AttwoollC. et al.

    Identification of a novel fusion gene involving hTAF1168 and CHN from a t(9;17)(g22;q11.2) translocation in an extraskeletal myxoidchondrosarcoma

    Oncogene

    (1999)
  • ZucmanJ. et al.

    EWS and ATF-1 gene fusion induced by [(12;22) translocation in malignant melanoma of soft parts

    Nat Genet

    (1993)
  • ClarkJ. et al.

    Identification of novel genes, SYT and SSX, involved in t(x; 18) (p11.2;g11.2) translocation found in human synovial sarcoma

    Nat Genet

    (1994)
  • CrewA.J. et al.

    Fusion of SYT to two genes, SSXI and SSX2, encoding proteins with homology to the kruppel-associated box in human synovial sarcoma

    EMBO J

    (1995)
  • De LeeuwB. et al.

    Identification of two alternative fusion genes, SYT-SSXI and SYT-SSX2, in [(X;18) (p11.2;g11.2)-positive synovial sarcomas

    Hum Mol Genet

    (1995)
  • SkyttingB. et al.

    A novel fusion gene, SYT-SSX4, in synovial sarcoma

    J Natl Cancer Inst

    (1999)
  • GaliliN. et al.

    Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhadomyosarcoma

    Nat Genet

    (1993)
  • ShapiroD. et al.

    Fusion of PAX3 to a member of the forkhead family of transcription factors in human alveolar rhadomyosarcoma

    Cancer Res

    (1993)
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