ABSTRACT
One of the most exciting areas of molecular oncology is the convergence of two independent lines of evidence suggesting involvement of multiple tumor suppressor genes in a given type of cancer. First, epidemiology and somatic cell genetics indicate the presence of multiple tumor suppressor genes in each of several malignancies. Second, cancers often lose multiple chromosomal regions during tumor progression. We will use two tumors, colorectal cancer and Wilms tumor, to illustrate the questions that multiple tumor suppressor genes raise.
Subject(s)
Colorectal Neoplasms/genetics , Gene Deletion , Genes, Tumor Suppressor , Kidney Neoplasms/genetics , Wilms Tumor/genetics , DNA, Neoplasm/metabolism , Humans , MethylationABSTRACT
Wilms tumor is an embryonal kidney tumor involving complex pathology and genetics. The Wilms tumor locus on chromosome 11p13 is defined by the region of overlap of constitutional and tumor-associated deletions. Chromosome walking and yeast artificial chromosome (YAC) cloning were used to clone and map 850 kilobases of DNA. Nine CpG islands, constituting a "CpG island archipelago," were identified, including three islands that were not apparent by conventional pulsed-field mapping, and thus were at least partially methylated. Three distinct transcriptional units were found closely associated with a CpG island within the boundaries of a homozygous DNA deletion in a Wilms tumor.
