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Combined physical and genetic map finds cancer's 'ignition key'
Date:5/5/2008

egion on chromosome 13, which they knew harbored the tumor-suppressor RB1, for high-resolution genetic analysis to identify candidate genes affecting RB1 by using single-nucleotide polymorphisms (SNPs) as markers. SNPs are points in the genome that vary by a single DNA chemical building block or nucleotide.

They examined 92 SNPs mapping to a region around the RB1 gene in 84 paired samples of bladder tumors and blood DNA. This high-resolution genetic analysis pointed to the same section of the chromosome that whole organ histologic and genetic mapping had identified with expansion of abnormal cells.

Two genes in the region were found to give cells an initial minimum genetic advantage needed to grow into cancer.

A neighboring gene called ITM2B was found to be silenced by methylation, which is the connection of a methyl chemical group to portions of the gene that shuts it down. In bladder cancer tumors and cancer cell lines, this gene was methylated 40 percent of the time.

A gene known as P2RY5 located inside a portion of the RB1 gene was affected by a number of single-nucleotide changes. A case-control study of one of the genes variant forms was conducted using blood DNA from 790 bladder cancer patients and 712 controls matched for age and gender. The specific variation was present in 2.78 percent of patients and every patient with the variation who also smoked developed bladder cancer.

The forerunner genes identified in bladder cancer were analyzed for their expression, methylation and sequence in 62 cell lines derived from major groups of common cancers. Of the cell lines tested, forerunner gene expression was reduced in 63 percent of the cases and ITM2B was methylated in 42 percent.

While forerunner genes were downregulated in lung, breast, blood and pediatric malignancies, they were strongly expressed in colon and liver cancers. This makes sense, the researchers note, because those two cancers do not rely on inactivat
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Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert

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