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- Posted Wednesday May 23, 2012
TGen-Scottsdale Healthcare conduct whole genome sequencing of rare olfactory neuroblastoma
Analysis provides clues to possible precision medicine treatment
of rare nasal tract cancer
May 23, 2012
The Translational Genomics Research Institute (TGen) and the
Virginia G. Piper Cancer Center at Scottsdale Healthcare have
conducted whole genome sequencing (WGS) of a rare nasal tract
cancer called olfactory neuroblastoma (ONB).
Analysis of the billions of molecules that make up the patient's
normal DNA, and cancerous DNA, discovered genetic mutations that
could be future targets of advanced precision-medicine drug
development.
Results of the study appeared today in the on-line journal Public
Library of Science (PLoS) One.
"Currently, physicians have few choices when formulating a
treatment plan for a patient with advanced cancer, especially in
cases of rare cancers," said Dr. Glen Weiss, the paper's lead
author. He holds joint appointments at TGen and at the Virginia G.
Piper Cancer Center Clinical Trials, a partnership between
Scottsdale Healthcare and TGen that treats cancer patients with
promising new drugs.
"There has been no comprehensive genomic sequencing study to
identify mutation profiles of these rare ONB cancers in order to
identify therapeutic targets for treating these patients," said Dr.
Weiss, Director of Thoracic Oncology at the Virginia G. Piper
Cancer Center, and a Clinical Associate Professor in TGen's Cancer
and Cell Biology Division.
Personalized medicine involves precise drugs aimed at specific
genetic targets intended to shrink, and even eliminate, tumors
without the debilitating toxic side effects of conventional
chemotherapies.
The study involved a 29-year-old man who presented at the Virginia
G. Piper Cancer Center at Scottsdale Healthcare following years of
standard-of-care treatment involving surgery, radiation and
conventional chemotherapy. His metastatic ONB had continued to
mutate and return, resulting in deforming lesions and extensive
surgeries that required plastic reconstruction.
His biopsied tumor and blood were analyzed at TGen, which spelled
out the billions of individual molecular bases in the DNA of the
patient's tumor, and in his normal DNA. A comparison identified
several significant gene mutations, including: MAP4K2, SIN3B,
TAOK2, KDR, TP53, MYC, and NLRC4. These were selected based on
clinical relevance and previously published literature on the
target genes and their association with carcinogenesis, or the
creation and evolution of cancer.
"The mutated target genes implicate aberrations in DNA repair
mechanisms and apoptosis," said Dr. John Carpten, the paper's
senior author. He is a Professor and Director of TGen's Integrated
Cancer Genomics Division and Deputy Director of Research for TGen.
"This work provides novel insights into the underpinnings of a rare
but terrible form of cancer. Hopefully we can translate these
findings into tools for improved clinical management of rare tumors
such as this."
The paper cites the need for additional study of how the ONB cancer
mutates and progresses, and how whole genome sequencing can play an
important role in future analysis.
"With the reduction in cost, improvement in speed of analysis and
with more complete understanding of complex genetic alterations, we
anticipate that WGS will be applied in the clinic more frequently
to common and rare cancers and will pave the way to personalized
medicine," Dr. David Craig, another of the paper's senior authors.
He is an Associate Professor and Associate Director of TGen's
Neurogenomics Division.
The paper, "Paired tumor and normal whole genome sequencing of
metastatic olfactory neuroblastoma," was part of a pilot study
entitled, "An Ancillary Pilot Trial Using Whole Genome Tumor
Sequencing in Patients with Advanced Refractory Cancer."
The National Foundation for Cancer Research, and the TGen
Foundation, funded the study.
"This study represents a milestone in cancer research, and is about
better treatments - and even cures - for cancer through
genomics-based personalized medicine," said Franklin C. Salisbury
Jr., President of the National Foundation for Cancer Research.
"Whole genome sequencing is giving scientists a better
understanding of the genetic basis of many cancers. Based on
mutations uncovered by sequencing, doctors will be able to identify
both existing anti-cancer drugs, or new anti-cancer drugs, designed
to target those very mutations. This is Research for a Cure."
About the Virginia G. Piper Cancer Center at Scottsdale
Healthcare
The Virginia G. Piper Cancer Center at Scottsdale Healthcare in
Scottsdale, Ariz. offers comprehensive cancer care and research
through Phase I clinical trials, diagnosis, treatment, prevention
and support services in collaboration with leading scientific
researchers and community oncologists. Scottsdale Healthcare is the
nonprofit parent organization of the Virginia G. Piper Cancer
Center at Scottsdale Healthcare, Scottsdale Healthcare Research
Institute, Scottsdale Healthcare Osborn Medical Center, Scottsdale
Healthcare Shea Medical Center and Scottsdale Healthcare Thompson
Peak Hospital. For more information, visit www.shc.org.
Press Contact:
Jamie Houston
Public Relations Coordinator
Virginia G. Piper Cancer Center
480-323-1387
[email protected]
About TGen
The Translational Genomics Research Institute (TGen) is a Phoenix,
Arizona-based non-profit organization dedicated to conducting
groundbreaking research with life changing results. Research at
TGen is focused on helping patients with diseases such as cancer,
neurological disorders and diabetes. TGen is on the cutting edge of
translational research where investigators are able to unravel the
genetic components of common and complex diseases. Working with
collaborators in the scientific and medical communities, TGen
believes it can make a substantial contribution to the efficiency
and effectiveness of the translational process. For more
information, visit: www.tgen.org.
Press Contact:
Steve Yozwiak
TGen Senior Science Writer
602-343-8704
[email protected]