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Home > G. Tumoral pathology > Molecular pathology of tumors > Genetic anomalies > Cancer cytogenetics > tumoral chromosomal rearrangements

tumoral chromosomal rearrangements

Friday 29 August 2008

Reciprocal translocations, inversions, and insertions are typical chromosomal rearrangements. There is substantial evidence that these alterations are early or even initiating events in tumorigenesis.

For instance, certain translocations that are associated with childhood leukemia arise in utero, years before the appearance of overt disease.

Furthermore, most chromosomal rearrangements are closely associated with specific tumor types, even though individual genes — such as MLL, ETV6, and NUP98 — can participate in multiple different translocations, sometimes with distinct clinicopathological associations.

Notably, certain chromosomal rearrangements, such as the BCR-ABL1 fusion gene, serve as sensitive indicators in the assessment of the response to cancer treatment.7

With regard to their functional consequences, recurrent chromosomal rearrangements are of two general types: aberrations that result in the formation of a chimeric fusion gene with new or altered activity and chromosomal changes that lead to deregulated expression.


- Formation of a chimeric fusion gene

Chromosomal rearrangements can result in the formation of a chimeric fusion gene.

Rearrangements leading to the expression of a chimeric protein with constitutive tyrosine kinase activity in the absence of physiologic activating signals. For example, the translocation t(9;22)(q34.1;q11.23) is associated with chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL).

Rearrangements leading to the expression of a chimeric protein with aberrantly increased transcriptional activity are represented by the translocation t(11;22)(q24.1-q24.3;q12.2) associated with Ewing’s sarcoma.

Rearrangements leading to the expression of a chimeric protein that mediates aberrant transcriptional repression through interaction with chromatin-modifying proteins are represented by the translocation t(15;17)(q22;q21) associated with acute promyelocytic leukemia (APL).

See: chimeric fusion genes

- Deregulated expression of a structurally normal gene

Chromosomal rearrangements can also result in deregulated expression of a structurally normal gene.

In Burkitt lymphoma, the translocation t(8;14)(q24.21;q32.33) leads to the aberrant juxtaposition of the enhancer of the IGHG1 gene on band 14q32.33 with the coding sequence of the MYC gene on band 8q24.21, resulting in overexpression of the MYC transcription factor in lymphoid tissues.

In prostate cancer, a small interstitial deletion or cryptic insertion involving chromosome band 21q22.3 fuses androgen-regulated sequences in the promoter of the prostate-specific TMPRSS2 gene to the coding region of the ERG gene, resulting in aberrant expression of the ERG transcription factor in prostate tissue.

See: deregulated genic expression


Until recently, chromosomal rearrangements have been linked mainly to hematologic cancers and tumors of mesenchymal origin. However, a number of recent studies have shown that genomic rearrangements that juxtapose two genes also play major roles in the pathogenesis of epithelial cancers, such as prostate cancer and non–small-cell lung cancer.

It is possible that similar rearrangements in other solid tumors exist but have escaped notice because of technical problems, such as the difficulty in growing tumor cells for chromosomal analysis, or because they are cytogenetically invisible or masked by multiple complex and often nonspecific karyotypic changes, which are thought to reflect secondary genetic events acquired during tumor progression.


- translocation-associated tumors

  • translocation-associated leukemias
  • translocation-associated lymphomas
  • translocation-associated sarcomas
  • translocation-associated carcinomas


- Fröhling S, Döhner H. Chromosomal abnormalities in cancer. N Engl J Med. 2008 Aug 14;359(7):722-34. PMID: 18703475