Cytogenetics and fusion transcripts

These sites give comprehensive information on cytogenetics of tumours, with a search engine that allows you to search by tumour type of cytogenetic aberration: http://cgap.nci.nih.gov/Chromosomes/Mitelman , http://amba.charite.de/cgh and http://www.progenetix.net.

Sarcomas:

 

Tumour

Chromosomal abnormality

Fusion transcript

this translocation has also been reported in:

  

Ewing sarcoma / PNET

t(11;22)(q24;q12)1

EWS-FLI11

two polyphenotypic tumours and two rhabdomyosarcomas20

t(21;22)(q22;q12)2

EWS-ERG2

  

t(7;22)(p22;q12)3

EWS-ETV13

  

t(17;22)(q12;q12)

EWS-E1AF4

  

t(2;22)(q33;q12)5

EWS-FEV5

  

Desmoplastic small round cell tumour

t(11;22)(p13;q12)6

EWS-WT16

  

t(21;22)(q22;q12)

EWS-ERG7

  

Synovial sarcoma

t(X;18)(p11.23;q11)8,9

SYT-SSX1

  

t(X;18)(p11.21;q11)8,9

SYT-SSX2

  

Alveolar rhabdomyosarcoma

t(2;13)(q35;q14)10,11

PAX3-FKHR10 (a.k.a. PAX3-ALV11)

  

t(1;13)(p36;q14)12

PAX7-FKHR12

  

2p2318

ALK18

  

Alveolar soft part sarcoma

der(17), t(X;17)(p11;q25)

TFE3/ASPL (a.k.a. ASP-SCR1, RCC17)

  

Clear cell sarcoma

t(12;22)(q13;q12)19

ATF1-EWS19

  

Myxoid / round cell liposarcoma

t(12;16)(q13;p11)13,14

TLS/FUS-CHOP13,14

  

t(12;22)(q13;q12)15

EWS-CHOP15

  

Extraskeletal myxoid chondrosarcoma

t(9;22)(q22;q12)19

TEC-EWS19

  

Low-grade fibromyxoid sarcoma

t(7;16)(q33;p11)19

FUS-CREB3L219

  

Dermatofibrosarcoma protuberans

t(17;22)(q22;13)19

COL1A1-PDGFB19

  

Inflammatory myofibroblastic tumour

t(2;19)(p23;q13.1)19

ALK-TPM419

  

t(1;2)(q22-23;p23)19

TPM3-ALK19

  

Infantile fibrosarcoma

t(12;15)(p13;q25)19

ETV6-NTRK319

  

Congenital fibrosarcoma and mesoblastic nephroma

t(12;15)(p13;q25)16,17

ETV6-NTRK316,17

  
       

Some sarcomas show complex karyotypes and non-specific alterations, often in association with p53 mutations19:

 

High grade pleomorphic sarcoma in adults

  

Leiomyosarcoma

Malignant peripheral nerve sheath tumour

Angiosarcoma

Osteosarcoma
 

Benign mesenchymal tumours commonly show tranlocations involving the high mobility genes21:

 

Tumour

Chromosomal abnormality

Involved gene

  

Uterine leiomyoma

t(12q13-15;x)

HMG1-C

  

t(6p21;x)

HMG1(Y)

  

Sporadic lipoma

t(12q13-15) with chromosomes 1 thro' 7, 10,11,13, 15, 17,21 or X

HMG1-C

  

t(6p21;x)

possibly HMG1(Y)

  

Lipoblastoma

8q

?

  

Hibernoma

t(11q13;x)

?

  

Fibroadenoma

t(12q13-15;x)

HMG1-C

  

Pleomorphic adenoma

t(12q13-15;x)

HMG1-C

  

t(3;8)(p21;q12)

PLAG1

  

Pulmonary chondroid hamartoma

t(12q13-15;x)

HMG1-C

  

inv(6p21)

HMG1(Y)

  

t(6p21;x)

HMG1(Y)

  

Aggressive angiomyxoma

t(12q13-15;x)

HMG1-C

  

Endometrial polyp

t(12q13-15;x)

HMG1-C

  

t(6p21;x)

possibly HMG1(Y)

  

Chondroma

t(12q13-15;x)

HMG1-C

  
       

References

1 Delattre, O., J. Zucman, et al. (1992). "Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours." Nature 359(6391): 162-5.

2 Sorensen, P. H., S. L. Lessnick, et al. (1994). "A second Ewing's sarcoma translocation, t(21;22), fuses the EWS gene to another ETS-family transcription factor, ERG." Nat Genet 6(2): 146-51.

3 Jeon, I. S., J. N. Davis, et al. (1995). "A variant Ewing's sarcoma translocation (7;22) fuses the EWS gene to the ETS gene ETV1." Oncogene 10(6): 1229-34.

4 Urano, F., A. Umezawa, et al. (1996). "A novel chimera gene between EWS and E1A-F, encoding the adenovirus E1A enhancer-binding protein, in extraosseous Ewing's sarcoma." Biochem Biophys Res Commun 219(2): 608-12.

5 Peter, M., J. Couturier, et al. (1997). "A new member of the ETS family fused to EWS in Ewing tumors." Oncogene 14(10): 1159-64.

6 Ladanyi, M. and W. Gerald (1994). "Fusion of the EWS and WT1 genes in the desmoplastic small round cell tumor." Cancer Res 54(11): 2837-40.

7 Ordi, J., E. de Alava, et al. (1998). "Intraabdominal desmoplastic small round cell tumor with EWS/ERG fusion transcript." Am J Surg Pathol 22(8): 1026-32.

8 de Leeuw, B., W. Berger, et al. (1993). "Identification of a yeast artificial chromosome (YAC) spanning the synovial sarcoma-specific t(X;18)(p11.2;q11.2) breakpoint." Genes Chromosomes Cancer 6(3): 182-9.

9 de Leeuw, B., R. F. Suijkerbuijk, et al. (1993). "Sublocalization of the synovial sarcoma-associated t(X;18) chromosomal breakpoint in Xp11.2 using cosmid cloning and fluorescence in situ hybridization." Oncogene 8(6): 1457-63.

10 Galili, N., R. J. Davis, et al. (1993). "Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhabdomyosarcoma." Nat Genet 5(3): 230-5.

11 Shapiro, D. N., J. E. Sublett, et al. (1993). "Fusion of PAX3 to a member of the forkhead family of transcription factors in human alveolar rhabdomyosarcoma." Cancer Res 53(21): 5108-12.

12 Davis, R. J., C. M. D'Cruz, et al. (1994). "Fusion of PAX7 to FKHR by the variant t(1;13)(p36;q14) translocation in alveolar rhabdomyosarcoma." Cancer Res 54(11): 2869-72.

13 Crozat, A., P. Aman, et al. (1993). "Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma." Nature 363(6430): 640-4.

14 Rabbitts, T. H., A. Forster, et al. (1993). "Fusion of the dominant negative transcription regulator CHOP with a novel gene FUS by translocation t(12;16) in malignant liposarcoma." Nat Genet 4(2): 175-80.

15 Panagopoulos, I., M. Hoglund, et al. (1996). "Fusion of the EWS and CHOP genes in myxoid liposarcoma." Oncogene 12(3): 489-94.

16 Knezevich, S. R., M. J. Garnett, et al. (1998). "ETV6-NTRK3 gene fusions and trisomy 11 establish a histogenetic link between mesoblastic nephroma and congenital fibrosarcoma." Cancer Res 58(22): 5046-8.

17 Rubin, B. P., C. J. Chen, et al. (1998). "Congenital mesoblastic nephroma t(12;15) is associated with ETV6-NTRK3 gene fusion: cytogenetic and molecular relationship to congenital (infantile) fibrosarcoma." Am J Pathol 153(5): 1451-8.

18 Cessna, M. H., H. Zhou, et al. (2002). "Expression of ALK1 and p80 in inflammatory myofibroblastic tumor and its mesenchymal mimics: a study of 135 cases." Mod Pathol 15(9): 931-8.

19 Hahn HP, Fletcher CDM. The role of cytogenetics and molecular genetics in soft tissue tumour diagnosis - a realistic approach. Current Diagnsotic Pathology 2005;11:361-370.

20 Thorner P, Squire J, Chilton-MacNeil S, et al. Is the EWS/FLI-1 fusion transcript specific for Ewing sarcoma and peripheral primitive neuroectodermal tumor? A report of four cases showing this transcript in a wider range of tumor types. Am J Pathol 1996; 148:1125-38

21 Hess JL. Chromosomal translocations in benign tumors: the HMGI proteins. Am J Clin Pathol 1998; 109:251-61

This page last revised 27.11.2005.

©SMUHT/PW Bishop