Comprehensive clinical sequencing opens door to the promise of precision medicine

Date:
July 25, 2021
Source:
St. Jude Children's Research Hospital
Summary:
A new study highlights the power of comprehensive whole genome,
whole exome and RNA sequencing to better understand and treat each
patient's cancer.



FULL STORY ==========================================================================
St. Jude Children's Research Hospital investigators have demonstrated
that comprehensive genomic sequencing of all pediatric cancer patients
is feasible and essential to capitalize on the lifesaving potential of precision medicine.

Results from the St. Jude Genomes for Kids study appear online today in
the journal Cancer Discovery.


========================================================================== Whole genome and whole exome sequencing of germline DNA was offered to
all 309 patients who enrolled in the study. Whole genome, whole exome
and RNA sequencing of tumor DNA was carried out for the 253 patients
for whom adequate tumor samples were available.

Overall, 86% of patients had at least one clinically significant variation
in tumor or germline DNA. Those included variants related to diagnosis, prognosis, therapy or cancer predisposition. Researchers estimated that
1 in 5 patients had clinically relevant mutations that would have gone undetected using standard sequencing methods.

"Some of the most clinically relevant findings were only possible
because the study combined whole genome sequencing with whole exome
and RNA sequencing," said Jinghui Zhang, Ph.D., St. Jude Department of Computational Biology chair and co-corresponding author of the study.

Every tumor is unique. Every patient is unique.

Comprehensive clinical sequencing that includes whole genome, whole
exome and RNA sequencing is not widely available. But as the technology
becomes less expensive and accessible to more patients, researchers said comprehensive sequencing will become an important addition to pediatric
cancer care.



==========================================================================
"We want to change the thinking in the field," said David Wheeler,
Ph.D., St.

Jude Precision Genomics team director and a co-author of the study. "We
showed the potential to use genomic data at the patient level. Even in
common pediatric cancers, every tumor is unique, every patient is unique.

"This study showed the feasibility of identifying tumor vulnerabilities
and learning to exploit them to improve patient care," he said.

Tumor sequencing guided the change in treatment for 12 of the 78
study patients for whom standard of care was unsuccessful. In four of
the 12 patients, the changes stabilized disease and extended patient
lives. Another patient, one with acute myeloid leukemia, went into
remission and was cured by blood stem cell transplantation.

"Through the comprehensive genomic testing in this study, we were able
to clearly identify tumor variations that could be treated with targeted agents, opening doors for how oncologists manage their patients," said co-corresponding author Kim Nichols, M.D., St. Jude Cancer Predisposition Division director.

Additional findings and details Genomes for Kids enrolled patients
between August 2015 and March 2017.



========================================================================== Eighteen percent of patients carried germline variations in one of 156
known, cancer-predisposition genes.

Almost two-thirds of the germline variations identified would not have
been detected based on current screening guidelines.

Next steps Genomes for Kids helped launch the hospital's clinical genomics program, which has enrolled about 2,700 cancer patients to date.

Meanwhile, data generated through the Genomes for Kids study are
available at no cost to the international research community. By sharing
the data, St. Jude aims to speed advances in understanding and treatment
of pediatric cancer. The data are available in St. Jude Cloud.

"Even the most treatable cancers are not curable in all
patients. For example, relapse remains the leading cause of
death for the most common childhood cancer, acute lymphoblastic
leukemia," Nichols said. "Being able to understand and predict
which patients will respond to treatment and which won't
requires collecting comprehensive genomic data on all patients." ========================================================================== Story Source: Materials provided by
St._Jude_Children's_Research_Hospital. Note: Content may be edited for
style and length.


========================================================================== Journal Reference:
1. Scott Newman, Joy Nakitandwe, Chimene A Kesserwan, Elizabeth
M Azzato,
David A Wheeler, Michael Rusch, Sheila Shurtleff, Dale J Hedges,
Kayla V Hamilton, Scott G Foy, Michael N Edmonson, Andrew Thrasher,
Armita Bahrami, Brent A Orr, Jeffery M Klco, Jiali Gu, Lynn W
Harrison, Lu Wang, Michael R Clay, Annastasia Ouma, Antonina
Silkov, Yanling Liu, Zhaojie Zhang, Yu Liu, Samuel W Brady, Xin
Zhou, Ti-Cheng Chang, Manjusha Pande, Eric Davis, Jared Becksfort,
Aman Patel, Mark R Wilkinson, Delaram Rahbarinia, Manish Kubal,
Jamie L Maciaszek, Victor Pastor, Jay Knight, Alexander M Gout,
Jian Wang, Zhaohui Gu, Charles G Mullighan, Rose B McGee, Emily A
Quinn, Regina Nuccio, Roya Mostafavi, Elsie L Gerhardt, Leslie M
Taylor, Jessica M Valdez, Stacy J Hines-Dowell, Alberto S Pappo,
Giles Robinson, Liza-Marie Johnson, Ching-Hon Pui, David W Ellison,
James R Downing, Jinghui Zhang, Kim E Nichols. Genomes for Kids:
The scope of pathogenic mutations in pediatric cancer revealed
by comprehensive DNA and RNA sequencing. Cancer Discovery, 2021;
candisc.1631.2020 DOI: 10.1158/2159-8290.CD-20-1631 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/07/210725102500.htm

--- up 11 weeks, 2 days, 22 hours, 45 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)