Lund Virtual Medical Journal
Faculty of Medicine, Lund University, Sweden
| Article of the month - Issue April 2004 | ||
| Fusion genes and rearranged genes as a linear function of chromosome aberrations in cancer. Mitelman F, Johansson B, Mertens F Source: Nat Genet. 2004 Apr;36(4):331-4. 
Felix Mitelman, Bertil Johansson and Fredrik Mertens This is a study showing the potential to achieve a sufficient sample size to support new hypotheses when creating an Internet-based research database. The Mitelman Database of Chromosome Aberrations in Cancer (http:/cgap.nci.nih.gov/Chromosomes/Mitelman) was established in the early 1980s and a compilation of all chromosomal breakpoints in human cancer was presented as a special issue of the journal Nature Genetics in 1997. In the current publication, the database helps the authors to support the hypothesis that there may not be any fundamental tissue-specific differences in the genetic mechanisms by which neoplasia is initiated. Fusion genes and genes rearranged as a consequence of balanced chromosome changes have previously been found in haematological malignancies, but this survey indicates that the same findings occur in solid tumours. Considering that malignant epithelial tumours represent the predominant cause of human cancer morbidity and mortality, the implication is not trivial, especially in view of recent progress in the development of treatment regimens specifically directed against the product of the pathogenetic gene fusions in malignant disorders. Structural balanced rearrangements are associated with distinct tumour subtypes with remarkable specificity and have been essential for identifying genes involved in tumorigenesis. All balanced rearrangements that have been characterized molecularly act by deregulating a gene in one of the breakpoints or by creating a fusion gene. Because most recurrent aberrations and rearranged genes have been found in haematological disorders, whereas numerous genomic imbalances have been identified in solid tumours, it has become generally accepted that there are pathogenetic differences between these neoplasms. The authors here show that in every tumour type, the numbers of recurrent balanced chromosome abnormalities, fusion genes and genes rearranged as a consequence of balanced aberrations are simply a function of the number of cases with an abnormal karyotype. Hence, there may not be any fundamental tissue-specific differences in the genetic mechanisms by which neoplasia is initiated. Article available by the kind permission of the copyright owner, Nature Publishing Group. |
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