Trends in Molecular Medicine
Volume 8, Issue 8, 1 August 2002, Pages 396-405
Journal home page for Trends in Molecular Medicine

Review
Reciprocal products of chromosomal translocations in human cancer pathogenesis: key players or innocent bystanders?

https://doi.org/10.1016/S1471-4914(02)02384-5Get rights and content

Abstract

Chromosomal translocations are frequently involved in the pathogenesis of leukemias, lymphomas and sarcomas. They can lead to aberrant expression of oncogenes or the generation of chimeric proteins. Classically, one of the products is thought to be oncogenic. For example, in acute promyelocytic leukaemia (APL), reciprocal chromosomal translocations involving the retinoic acid receptor α (RARα) gene lead to the formation of two fusion genes: X–RARα and RARα–X (where X is the alternative RARα fusion partner: PML, PLZF, NPM, NuMA and STAT 5b). The X–RARα fusion protein is indeed oncogenic. However, recent data indicate that the RARα–X product is also critical in determining the biological features of this leukemia. Here, we review the current knowledge on the role of reciprocal products in cancer pathogenesis, and highlight how their expression might impact on the biology of their respective tumour types.

Section snippets

The reciprocal fusion product ABL–BCR is frequently expressed in CML and retains the BCR domain with GTPase-activating function

CML is a malignant myeloproliferative disease characterized by the hyperplasia of well differentiated myeloid cells and by its association with chromosomal translocation between chromosomes 9 and 22 [t(9;22)], which generates the Philadelphia (Ph) chromosome 10., 78.. This translocation creates two chimeric genes: the BCR–ABL on the derivative chromosome 22, and the ABL–BCR on the derivative chromosome 9 10., 11., 78.. The t(9;22) is the hallmark of CML. In 98% of CML patients it can be

Balanced or unbalanced forms of the t(X;17)(p11;q25) generating ASPL and TFE3 fusion genes are associated with distinct tumour types

Alveolar soft part sarcoma (ASPS) is a rare tumour that usually arises in the soft tissues of the upper and lower limbs [86]. It characteristically affects young adults (peak incidence age of between 15 and 35 years) and the majority of patients present advanced-stage disease. The disease has a relatively indolent clinical course but long-term mortality is high because of chemoresistance of metastatic disease [86]. ASPL has distinctive histopathological features: these tumours are made of oval

Concluding remarks

Although a considerable number of human cancers are associated with reciprocal chromosomal translocations, the detection of the products encoded by both derivatives is infrequent. Notably, however, the reciprocal product is more often expressed in hematological malignancies. Among the leukaemias, both products are frequently detected in APL and CML. Experimental data obtained in transgenic models of APL suggest that the expression of the reciprocal product influence disease penetrance,

Acknowledgements

We thank Marc Ladanyi for critical reading of the manuscript. This work is supported by the NCI, the De Witt Wallace Fund for Memorial Sloan-Kettering Cancer Center, the Mouse Model of Human Cancer Consortium (MMHCC), NIH Grants to P.P.P. and the Lymphoma and Leukemia Society of which P.P.P. is a Scholar. E.M.R. is the recipient of a grant from the ‘Fundação de Amparo a Pesquisa do Estado de São Paulo – FAPESP’ (Proc. 98/14247–6).

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