New approach to study molecular journey finds cancer's 'ignition key'

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Washington, May 6 : A whole-organ genomic survey has given an international team of researchers, including a scientist of Indian origin, significant insights into how a normal cell grows into bladder cancer.

Led by scientists at The University of Texas M. D. Anderson Cancer Center, the researcher team geographically related the organ's varied tissues-normal, pre-cancerous, and malignant-to their underlying genetic variation or regulation.

This helped the researchers identify a crucial new category of genes that launches the process of cancer development, they said.

"These 'forerunner genes' are the ignition key that starts the engine of carcinogenesis," said Bogdan Czerniak, a professor in M. D. Anderson's Department of Pathology, and senior author of the study reported online in the journal Laboratory Investigation.

"Discovery of forerunner genes opens an entirely new field of investigation to identify biomarkers for the early detection and prevention of cancer. Inactivation of these genes occurs during cancer's invisible stage, when it is undetectable by traditional means," Czerniak said.

The researchers say that forerunner genes must be shut down before a major tumour-suppressing gene called RB1 is silenced, paving the way for invasive cancer.

By characterizing the genetic aspects of all tissue types in the bladder, the researcher could identify three "waves" genetic hits that drive the molecular journey from a normal cell to invasive cancer.

Czerniak calls his unique approach whole organ histologic and genetic mapping, which combines genetic information with microscopic study of the organ tissue, or histology.

Dr. T. Sudhir Srivastava, chief of the Cancer Biomarkers Research Group, Division of Cancer Prevention of the National Cancer Institute, terms Czerniak's mapping techniques and the team's findings "seminal work".

"Identifying genes involved in pre-cancerous development has been an arduous task, primarily for lack of a systematic approach to discovering them and the non-availability of quality tumour specimens," Srivastava said.

"Dr. Czerniak has overcome these difficulties by utilizing the resources available at M. D. Anderson and employing the gene-mapping expertise of his group to uniquely characterize chromosomal regions involved in genomic imbalances, particularly those involved in progression of precancerous conditions to clinically aggressive bladder cancer.

"These findings will accelerate the development of clinically useful biomarkers for the early detection, surveillance, and clinical management of bladder cancer," he added.

The investigators insist that their research model may be useful in studying other cancers also because silenced forerunner genes involved in early development of bladder cancer also are silenced to varying degrees in lung, breast, blood and common pediatric malignancies.

"It took us 10 years to get where we are now. With the new high-throughput technology now available, we will complete a high-resolution genetic map of the entire genome for bladder cancer in the next two or three years," Czerniak said.

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