Chapter 079. Cancer Genetics (Part 8)

Table 79-3 Representative Oncogenes at Chromosomal Translocations Gene (Chromosome) Translocation Malignancy ABL BCR (22q11) ()– (9;22)(q34;q11) Chronic myelogenous leukemia ATF1 EWS (22q12) (12q13)– (12;22)(q13;q12) Malignant melanoma of soft parts (MMSP) BCL1 IgH (14q32) ()– (11;14)(q13;q32) Mantle lymphoma cell BCL2 IgH (14q32) ()– (14;18)(q32;q21) Follicular lymphoma FLI1 EWS (22q12) (11q24)– (11;22)(q24;q12) Ewing's sarcoma LCK TCRB (7q35) (1p34)– (1;7)(p34;q35) T lymphocytic (ALL) cell acute leukemia MYC (14q32) (8q24)–IgH (8;14)(q24;q32) Burkitt's B cell ALL lymphoma, WT1 EWS (22q12) (11p13)– (11;22)(p13;q12) Desmoplastic small round cell tumor (DSRCT) PAX3 (2q35)– (2;13)(q35;q14) Alveolar FKHR/ALV(13q14) rhabdomyosarcoma PAX7 (1p36)– (1;13)(p36;q14) Alveolar rhabdomyosarcoma KHR/ALV(13q14) RET () . | Chapter 079. Cancer Genetics Part 8 Table 79-3 Representative Oncogenes at Chromosomal Translocations Gene Chromosome Translocation Malignancy ABL - BCR 22q11 9 22 q34 q11 Chronic myelogenous leukemia ATF1 12q13 - EWS 22q12 12 22 q13 q12 Malignant melanoma of soft parts MMSP BCL1 IgH 14q32 - 11 14 q13 q32 Mantle cell lymphoma BCL2 IgH 14q32 - 14 18 q32 q21 Follicular lymphoma FLI1 EWS 22q12 11q24 - 11 22 q24 q12 Ewing s sarcoma LCK TCRB 7q35 1p34 - 1 7 p34 q35 T cell acute lymphocytic leukemia ALL MYC 14q32 8q24 -IgH 8 14 q24 q32 Burkitt s lymphoma B cell ALL WT1 EWS 22q12 11p13 - 11 22 p13 q12 Desmoplastic small round cell tumor DSRCT PAX3 2q35 - 2 13 q35 q14 Alveolar FKHR ALV 13q14 rhabdomyosarcoma PAX7 1p36 - KHR ALV 13q14 1 13 p36 q14 Alveolar rhabdomyosarcoma RET 10 17 q23 Papillary thyroid carcinomas Source From R Hesketh The Oncogene and Tumour Suppressor Gene Facts Book 2d ed. San Diego Academic Press 1997 with permission. The first reproducible chromosome abnormality detected in human malignancy was the Philadelphia chromosome detected in CML. This cytogenetic abnormality is generated by reciprocal translocation involving the ABL oncogene a tyrosine kinase on chromosome 9 being placed in proximity to the BCR breakpoint cluster region on chromosome 22. Figure 79-7 illustrates the generation of the translocation and its protein product. The consequence of expression of the BCR-ABL gene product is the activation of signal transduction pathways leading to cell growth independent of normal external signals. Imatinib a drug that specifically blocks the activity of BCR-ABL has shown .