USE OF COMPARATIVE GENOMIC HYBRIDIZATION TO DETERMINE IF EXPOSED
AND UNEXPOSED TUMORS ARE DIFFERENT
Lee E. Moore PHD, MPH; Allan H. Smith MD, PHD; Alex Hernandez MPH; Omar Rey MD;
University of California Berkeley School of Public Health; Katterina Ferreccio MD, MPH
Gredis Groupo para Desarrollo de la Investigation en Salud; Clarence Eng; Fred Waldman MD,
PhD University of California San Francisco Cancer Center
The causal relationship between arsenic exposure in drinking water and bladder cancer has been
documented in Taiwan, Argentina, Chile, and Japan however the mechanism through which
arsenic causes cancer remains a mystery. Molecular epidemiology studies employing tumors
from exposed and unexposed individuals can be an excellent way to gain insight into chemical
carcinogenesis, especially when animal models are not appropriate. Here we will describe a
case-case study conducted in Argentina and Chile examining tumor DNA from individuals
exposed to high, medium, and low concentrations of arsenic in their drinking water. We
employed comparative genomic hybridization to screen for genetic aberrations throughout the
tumor genome. In this study, by comparing the DNA of arsenic exposed and unexposed tumors,
gross changes related to arsenic exposure can be found. Chromosomal areas that show losses
could be areas where tumor suppressor genes involved in arsenic carcinogenesis may lie.
Similarly, oncogenes that are amplified by arsenic exposure may be located within areas showing
gains. Also, demonstrating a difference in the distribution of genetic events between the two
groups of tumors would illustrate that the exposed and unexposed bladder tumors arise from
distinct etiologies and could justify a more detailed investigation of the tumor DNA at the
molecular level. Here the overall number of chromosome gains and losses in each exposure
group will be presented as well as a comparison of regional gains and losses for each
chromosome arm. The need for further genetic analyses of tumor DNA at the molecular level
will also be discussed.