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- Posted Wednesday March 19, 2014
TGen study identifies gene fusion as likely cause of rare type of thyroid cancer
Genomic sequencing of 62-year-old patient leads to new treatment option
PHOENIX, Ariz. - March 19, 2014 - In a
scientific first, the fusion of two genes, ALK and EML4, has been
identified as the genetic driver in an aggressive type of thyroid
cancer, according to a study by the Translational Genomics Research
Institute (TGen).
These groundbreaking findings are based on genetic sequencing of
tumor cells from a 62-year-old patient with an aggressive tall cell
variant of papillary thyroid cancer, according to the study
published Tuesday, March 18, in the World Journal of
Surgery, the official journal of the International Society of
Surgery.
The patient's thyroid cancer recurred after he had undergone
multiple operations, external beam radiation and chemotherapy, and
so the patient appeared to be a candidate for additional
study.
Following one surgery in June 2011, a sample of the patient's
tumor was obtained and studied by whole-genome sequencing, in which
TGen spells out, in order, the more than 3 billion chemical base
pairs that make up human DNA.
A comparison of the tumor DNA to the patient's normal DNA found 57
mutations in 55 genes of the cancer genome. The investigators also
found a rearrangement between two genes. This translocation
and fusion of EML4-ALK was identified as the genetic driver of the
patient's cancer.
"This is the first report of the whole genome sequencing of a
papillary thyroid cancer, in which we identified an EML4-ALK
translocation. This is important because we have a drug that can
target this fusion and treat the patient," said Dr. Michael J.
Demeure, Clinical Professor and Director of TGen's Rare Cancer
Unit, and the study's the study's principal investigator and lead
author. "This patient's tumor did not harbor more well-known gene
mutations that are associated with most thyroid cancers. These
findings suggest that this tumor has a distinct oncogenesis, or the
genetic cause of cancer."
There are few therapeutic options for patients with
radioiodine-resistant aggressive papillary thyroid cancer. The
EML4-ALK fusion appears in about 5 percent of lung cancers, which
are usually treated with a targeted drug known as crizotinib.
By identifying the EML4-ALK fusion in this study, TGen was able to
recommend crizotinib for this study's 62-year-old patient, whose
cancer then remained progression-free for more than 6 months.
"Whole-genomesequencing technologies offer the promise of
allowing for precision targeted treatment for human diseases,
including cancer," said Dr. JohnCarpten, TGen Deputy Director
of Basic Science, and Director ofTGen's Integrated Cancer
Genomics Division, and the study's senior author. "Through a
greater understanding of the molecularoncogenesisof a
specific cancer, one would hope to devise more effective,
individualizedtreatments."
Whole genome sequencing is particularly beneficial for patients
with relatively rare tumors, since they generally have less access
to new drug treatments often available through clinical trials,
according to the study, Whole-genome sequencing of an
aggressive BRAF wild-type papillary thyroid cancer identified
EML4-ALK translocation as a therapeutic target.
Also contributing to this study were physicians from Arizona
Oncology, and Scottsdale Pathology Consultants.
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About TGen
Translational Genomics Research Institute (TGen) is a Phoenix,
Arizona-based non-profit organization dedicated to conducting
groundbreaking research with life changing results. TGen is focused
on helping patients with cancer, neurological disorders and
diabetes, through cutting edge translational research (the process
of rapidly moving research towards patient benefit). TGen
physicians and scientists work to unravel the genetic components of
both common and rare complex diseases in adults and children.
Working with collaborators in the scientific and medical
communities literally worldwide, TGen makes a substantial
contribution to help our patients through 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]