An international team of researchers, including a
scientist of Indian origin have performed a whole organ genomic survey that has
given them new insights into the molecular basis of 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
"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.