https://health.ucsd.edu/news/releases/Pages/2018-08-08-genetic-mutations-of-appendix-cancer-identified-may-impact-treatment.aspx
UC San Diego Health
Genetic Mutations of
Appendix Cancer Identified, May Impact Treatment
Appendix cancer
is currently treated like colon cancer, but significant differences may alter
therapy choices
August 08, 2018
| Yadira Galindo
News_r
The
rarity of appendix cancer, accounting for less than 1 percent of tumors that
originate in the gastrointestinal tract, and the lack of scientific data for
this disease means that current treatment guidelines recommend applying
therapies to people with appendix cancer that are intended for those with colon
cancer.
To
understand why some patients with appendix cancer respond to standard treatment
while others do not, University of California San Diego School of Medicine and
Moores Cancer Center researchers, in collaboration with Foundation Medicine,
performed genetic profiling on 703 appendiceal tumors — the largest such study
of this disease to date — to compare mutations present in both cancer types
The
findings, published online August 8 in JCO Precision Oncology
, confirm that genetic mutations in appendix cancer are distinct
from those found in colon cancer and that mutations in the genes TP53
and GNAS are good predictors of survival among people with appendix
cancer.
“For
tumors that are rare like appendix cancer, obtaining molecular profiles will
help identify potential treatment options since we don’t have the clinical
trial data to help guide treatments as we do in common tumors,” said lead
author John Paul Shen, MD, a
postdoctoral fellow in the lab of co-author Trey Ideker, PhD, UC San Diego
School of Medicine professor of medicine. “Equally important, the mutation
profile can be used as a biomarker to separate high-risk patients, who need
intensive treatment, from low-risk patients who may not need such an intensive
treatment.”
The
retrospective study found that appendix cancer is comprised of five distinct
subtypes: mucinous adenocarcinomas (46 percent), adenocarcinomas (30 percent),
goblet cell carcinoids (12 percent), pseudomyxoma peritonei (7.7 percent) and
signet ring cell carcinomas (5.2 percent).
A
mutation in the gene GNAS, rare in colon cancer, was found to be quite
frequent in appendix cancer, especially in mucinous adenocarcinomas (52
percent) and pseudomyxoma peritonei (72 percent). Patients with tumors
harboring a GNAS mutation had a median survival of almost 10 years,
while those whose tumors had a TP53 mutation had median survival of only
three years. Patients who had neither gene mutation had a six-year median
survival rate.
“This
striking finding raises the question of whether patients with early stage, GNAS-mutant
tumors need to be treated with chemotherapy, as it is possible they could be
cured with surgery alone; a question we will focus on in our next study,” said
Shen.
“Understanding
the molecular differences between the subtypes of appendiceal tumors is an important
stepping stone for future clinical trials to develop and test different
therapeutic approaches that are specific to this disease,” said senior author
Olivier Harismendy, PhD, assistant professor of medicine at UC San Diego Moores
Cancer Center.
Co-authors
include: Justin K. Huang, Miriam T. Jacobs, Ingrid L Chen, David Xu, Joel
Baumgartner, Andrew Lowy, Paul Fanta, UC San Diego; Celina S.-P. Ang, Camille
J. Hardy-Abeloos, Mount Sinai Hospital; Jeffrey S. Ross, Mount Sinai Hospital
and Albany Medical College; Vincent A. Miller, Siraj M. Ali, and Sherri Z.
Millis, Foundation Medicine, Inc.
This
research was funded in part by the Career Development Grant from the Tower
Cancer Research Foundation, the National Cancer Institute (U54 CA209891, L30
CA171000, 2P30 CA023100, U01 CA196406) and the National Institute for General
Medical Sciences (P50 GM085764).
Disclosure: Trey Ideker is co-founder of Data4Cure,
Inc. and has an equity interest in the company. Ideker is also a scientific
advisor for Ideaya Biosciences, Inc., has an equity interest and receives
income. The terms of this arrangement has been reviewed and approved by UC San
Diego, in accordance with its conflict of interest policies.
