Cytogenetics and fusion transcripts

Thiese site gives 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