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Conquest - Timeline of Discovery: Colon Cancer

Making the Connection 2001-2008

Timeline of Discovery: Colon Cancer

Date: April 20, 2010

CRF Investigator: Victor Velculescu


2001-2002
Begins a genome-wide analysis of colon cancer to identify the compendium of
genetic changes related to the disease.

2003
Co-developed a computerized gene analysis system known as SAGE that allows investigators to study thousands of genes simultaneously, measure their expression, and quickly identify the differences between normal and cancer cells. The work earns him Popular Science’s Brilliant Ten Award as one of ten most important discoveries of the year.

Performed the first systematic analysis of a gene family in a human disease.
Analysis of the tyrosine kinome gene family uncovered mutations linked to 30
percent of colon cancers. The genes are known to be good therapeutic targets.

2004

Discovered mutations in six colon cancer-related genes called tyrosine phosphatases.
Normally, these genes turn off tumor growth, but in colon cancer, they don’t work
because they are altered. Blocking related proteins with drugs could counteract the
effect of the altered genes.

Identified mutations in the PIK3CA gene and linked it to the progression of colon
and other cancers. The PIK3CA is now recognized to be the most highly mutated
oncogene identified in human cancers.

One of only 15 researchers nationwide named a Pew Biomedical Scholar by the
Pew Charitable Trusts. The $240,000 award augments his cancer genetics research
for the next four years.

2005

Reports on cancer research to 50 Hill staffers during a Capitol Hill briefing on the
progress of research efforts to improve the health of the nations’ citizens.
Findings from the initial CRF grant lead to millions of dollars in additional
funding from the National Institutes of Health and private donors.

2006-2007
Is part of a team that reveals the genetic blueprint for colon and breast cancers.
Identifying about 100 broken genes for each cancer, the work is seen as a schematic to
the control center of these cancers. Later work finds the gene landscape to contain a
variety of different, less frequently occurring mutations which vary from patient to patient,
explaining why seemingly like cancers respond very differently to standard therapies.

2008

Is part of a team that deciphers the complete genetic blueprint for deadly pancreatic
and brain cancers. Believed to be the most comprehensive result to date for any tumor
type, the new map evaluated mutations in virtually all known human protein-encoding
genes, comprised of more than 20,000 genes, revealing a core set of regulatory gene
processes and pathways, about a dozen for each tumor type, that were altered in the
majority of tumors studied.

DEVELOPING A SIMPLE TEST FOR COLON CANCER
RESEARCH

Colon cancer is among the most common of all cancers. Johns Hopkins studies
of this cancer revealed it, as well all other cancers, as a genetic disease by
pinpointing a series of genetic alterations that lead to colon cancer.

TRANSLATION
Identifying the genetic mutations involved in the origination and progression of
colon cancer could lead to a non-invasive test to detect the disease in an early,
curable stage.

APPLICATION
A stool test that detects precancerous polyps in the colon and very early colon
cancers was developed based on Velculescu and team’s mutational analysis of
colon cancers. The test was licensed to and now distributed by Exact Science
Corporation. The test is now available to the general public and has been added
to the American Cancer Society’s colon cancer screening guidelines.

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