Download - Genes, chromosomes and cancerdownloads.hindawi.com/journals/acp/2004/491629.pdfGenes, chromosomes and cancer About 70 scientists recently attended the conference on “Aneuploidy and

Cellular Oncology 26 (2004) 167 167IOS Press

Editorial

Genes, chromosomes and cancer

About 70 scientists recently attended the conferenceon “Aneuploidy and Cancer” in Oakland, CA, whichwas organized by P. Duesberg and D. Rasnick fromthe University of California, Berkeley, and generouslysponsored by philanthropist Robert Leppo. The con-ference explored whether aneuploidy, i.e., specific ge-nomic imbalances, is a driving force behind the devel-opment of cancer. A century ago this theory was firstsuggested by the German biologist, Theodor Boveri,who hypothesized that the gain or loss of promotingand inhibiting chromosomes, respectively, results inaberrant cell division and tumorigenesis. Boveri sug-gested that “malignant tumors might be the result of acertain abnormal condition of the chromosomes whichmay arise from multipolar mitosis. Abnormal mitosismay bring about an immense number of different chro-mosome combinations, such combinations as wouldmake a cell into a tumor cell must occasionally occur”.Despite the fact that quantitative measurements of thenuclear DNA content unequivocally demonstrated thatcancer genomes are frequently aneuploid, the mainfocus of scientific research regarding the genetic ba-sis of cancer shifted towards the role and involvementof single, specific genes. This development was alsopromoted due to the emerging of molecular cloningand hence the identification of oncogenes and tumorsuppressor genes. However, the identification of cen-trosome abnormalities in tumors, the clarification thattelomere defects can result in unbalanced chromoso-mal translocations and genomic imbalances and theapplication of novel molecular cytogenetic techniqueshas clearly demonstrated that chromosomal aneuploi-dies play a central role in the genesis of epithelialtumors. Both, the successful implementation of nuclearand chromosomal aneuploidy as a molecular target forcancer diagnosis and prognostication has solidified thefundamental role of aneuploidy and rekindled researchinterest into its origin. Moreover, several clinical stud-

ies showed that aneuploidy played a role already atthe beginning of the multistep neoplastic process, i.e.in premalignant, preinvasive dysplastic lesions. Forinstance, numerous studies have shown that the spe-cific gain of chromosome 7 occurs in colonic polypsbefore mutational inactivation of the tumor suppres-sor gene p53. Similarly, in assumingly premalignantlesions of the oral mucosa, i.e. erythro- and leuko-plakias, cases of aneuploidy were shown to have a70% malignant transformation rate within 3 years anda similar mortality rate within 3 years of patients af-ter the development of a cancer. We now know thatthe dynamic genomes of pre/malignancies are definedby the sequential acquisition of chromosomal aneu-ploidies that are specific to a particular type of tumorand that are continuously selected for under conditionsof prevailing genomic or chromosomal instability. Theobservation that aneuploidy as an indicator of geneticinstability is an early event in the process of neoplas-tic transformation has stimulated new interest into thebiological processes that determine genetic instabil-ity. One of the goals of the conference was to discussthe relative role of aneuploidy and gene mutations fortumorigenesis, a question that was at times hotly con-tested. However, it should be obvious by now, thataneuploidy reflects a core genetic aberration that re-sults in cellular immortalization and transformation.We therefore hope that future conferences specificallydedicated to this problem will continue exploring anddiscussing the genetic basis of aneuploidy and thetranslational prospect of aneuploidy when applied tocancer screening, diagnosis, prognostication and ther-apeutic intervention.

A. Reith and T. Ried,Oslo and Bethesda, July 2004

E-mail: [email protected]; [email protected]

1570-5870/04/$17.00 2004 – IOS Press and the authors. All rights reserved

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