Bone and Soft Tissue: Ewing-like sarcoma

0000-00-00   Kelly M Bailey 

1.University of Pittsburgh School of Medicine, Department of Pediatrics, Division of Pediatric Hematology\/Oncology, Kelly.Bailey@chp.edu

Abstract

Ewing-like sarcoma is a recently defined subset of bone or soft tissue sarcomas. It is one of the pediatric small, round, blue cell tumors and is fusion gene-driven cancer. However, the driving fusions are distinct from that of the FET-ETS family rearrangements that define Ewing sarcoma (see separate entry for Ewing sarcoma).

Classification

Classification

Ewing-like sarcoma can arise in the bone or soft tissue.

Clinics and Pathology

Etiology

Ewing-like sarcomas are characterized by EWSR1/NFATC2 fusions, CIC fusions, or BCOR rearrangements.

Clinics

Ewing-like sarcoma is a very rare subtype of bone, soft tissue or visceral sarcoma.

Pathology

Small, round blue cells, with variable CD99 staining.

Treatment

Patients with Ewing-like sarcoma are currently treated following Ewing sarcoma therapy protocols. This may change over time as more is understood about the individual fusions driving Ewing-like sarcomas.

Prognosis

Survival is generally poorer for Ewing-like sarcomas compared to that of Ewing sarcoma. The exact prognoses for individual Ewing-like fusions types is still under investigation. In general, CIC-fused Ewing-like sarcomas have a very poor prognosis (

Cytogenetics

Note

Ewing-like sarcomas harbor distinct fusions from that of Ewing sarcoma:
t(X;4)(p11.4; q31.1) BCOR/MALM3
t(X;22)(p11.4;q13.2) ZC3H7B/BCOR
t(X;4)(q13.1; q35.2) CIC/FOXO4
t(4;15)(q35.2; q14)CIC/NUTM1
t(4;19)(q35.2; q13.2)CIC/DUX4
t(20;22)(q13.2;q12.2) EWSR1/NFATC2
and fusion BCOR/CCNB3 (Xp11.4-Xp11.22)

Genes Involved and Proteins

Gene name

EWSR1 (Ewing sarcoma breakpoint region 1)

Location

22q12.2

Protein description

Contains both a transcriptional activation domain and an RNA-binding domain.

Gene name

NFATC2 (Nuclear factor of activated T cells 2)

Location

20q13.2

Protein description

DNA binding protein, responsive to T-cell receptor signaling.

Gene name

BCOR (BCL6 corepressor)

Location

Xp11.4

Protein description

Suppresses some genes by interacting with proteins comprising DNA binding complexes.

Gene name

MAML3 (Mastermind like transcriptional coactivator 3)

Location

4q31.1

Protein description

Involved in the NOTCH pathway.

Gene name

CCNB3 (Cyclin B3)

Location

Xp11.22

Protein description

Cyclin family member; involved in cell cycle regulation.

Gene name

CIC (Capicua transcriptional repressor)

Location

19q13.2

Protein description

HMG-box family member.

Gene name

DUX4 (Double homeobox 4)

Location

4q35.2

Protein description

Associated with various forms of muscular dystrophy.

Gene name

ZC3H7B (Zinc Finger CCCH-type containing 7B)

Location

22q13.2

Protein description

Nuclear protein; Contains domains involved in protein-protein and protein-nucleic acid interactions.

Gene name

FOXO4 (Forkhead Box O4)

Location

Xq13.1

Protein description

Involved in cell growth and differentiation.

Gene name

NUTM1 (NUT midline carcinoma family member 1)

Location

15q14

Protein description

TERT expression regulation.

Result of the chromosomal anomaly