Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 7/2018

01-07-2018 | Gastrointestinal Oncology

Rates of TP53 Mutation are Significantly Elevated in African American Patients with Gastric Cancer

Authors: Elke J. A. H. van Beek, MD, Jonathan M. Hernandez, MD, Debra A. Goldman, MS, Jeremy L. Davis, MD, Kaitlin McLaughlin, MD, R. Taylor Ripley, MD, Teresa S. Kim, MD, Laura H. Tang, MD, PhD, Jaclyn F. Hechtman, MD, Jian Zheng, MD, Marinela Capanu, PhD, Nikolaus Schultz, PhD, David M. Hyman, MD, Marc Ladanyi, MD, Michael F. Berger, PhD, David B. Solit, MD, Yelena Y. Janjigian, MD, Vivian E. Strong, MD, FACS

Published in: Annals of Surgical Oncology | Issue 7/2018

Login to get access

Abstract

Background

Gastric adenocarcinoma is a heterogenous disease that results from complex interactions between environmental and genetic factors, which may contribute to the disparate outcomes observed between different patient populations. This study aimed to determine whether genomic differences exist in a diverse population of patients by evaluating tumor mutational profiles stratified by race.

Methods

All patients with gastric adenocarcinoma between 2012 and 2016 who underwent targeted next-generation sequencing of cancer genes by the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets platform were identified. Patient race was categorized as Asian, African American, Hispanic, or Caucasian. Fisher’s exact test was used to examine differences in mutation rates between racial designations for the most common mutations identified. The p values in this study were adjusted using the false discovery rate method.

Results

The study investigated 595 mutations in 119 patients. The DNA alterations identified included missense mutations (66%), frame-shift deletions (13%), and nonsense mutations (9%). Silent mutations were excluded. The most frequently mutated genes were ARID1A, CDH1, ERBB3, KRAS, PIK3CA, and TP53. Of these, TP53 was the most frequently mutated gene, affecting 50% of patients. The proportion of patients with TP53 mutations differed significantly between races (p = 0.012). The findings showed TP53 mutations for 89% (16/18) of the African American patients, 56% (10/18) of the Asian patients, 43% (9/21) of the Hispanic patients, and 40% (25/62) of the Caucasian patients.

Conclusions

Significantly higher rates of TP53 mutations were identified among the African American patients with gastric adenocarcinoma. This is the first study to evaluate tumor genomic differences in a diverse population of patients with gastric adenocarcinoma.
Literature
1.
World Health Organization. GLOBOCAN 2012: Stomach cancer estimated cancer incidence, mortality, and prevalence worldwide in 2012. http://​globocan.​iarc.​fr. Accessed 13 July 2017.
2.
Ohtsu A, Yoshida S, Saijo N. Disparities in gastric cancer chemotherapy between the East and West. J Clin Oncol. 2006;24:2188–96.CrossRefPubMed
3.
Allemani C, Weir HK, Carreira H, et al. Global surveillance of cancer survival 1995–2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2). Lancet. 2015;385:977–1010.CrossRefPubMed
4.
Strong VE, Song KY, Park CH, et al. Comparison of gastric cancer survival following R0 resection in the United States and Korea using an internationally validated nomogram. Ann Surg. 2010;251:640–6.CrossRefPubMed
5.
Noguchi Y, Yoshikawa T, Tsuburaya A, Motohashi H, Karpeh MS, Brennan MF. Is gastric carcinoma different between Japan and the United States? Cancer. 2000;89:2237–46.CrossRefPubMed
6.
You WC, Li JY, Zhang L, Jin ML, Chang YS, Ma JL, Pan KF. Etiology and prevention of gastric cancer: a population study in a high-risk area of China. Chin J Dig Dis. 2005;6:149–54.CrossRefPubMed
7.
Cancer Genome Atlas Research Network. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513:202–9.CrossRef
8.
Cristescu R, Lee J, Nebozhyn M, et al. Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes. Nat Med. 2015;21:449–56.CrossRefPubMed
9.
10.
Howard JH, Hiles JM, Leung AM, Stern SL, Bilchik AJ. Race influences stage-specific survival in gastric cancer. Am Surg. 2015;81:259–67.PubMed
11.
Cheng DT, Mitchell TN, Zehir A, et al. Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT): a hybridization capture-based next-generation sequencing clinical assay for solid tumor molecular oncology. J Mol Diagn. 2015;17:251–64.CrossRefPubMedPubMedCentral
12.
13.
DeSantis CE, Siegel RL, Sauer AG, Miller KD, Fedewa SA, Alcaraz KI, Jemal A. Cancer Statistics for African Americans, 2016: progress and opportunities in reducing racial disparities. CA Cancer J Clin. 2016;66:290–308.CrossRefPubMed
14.
Du XL, Lin CC, Johnson NJ, Altekruse S. Effects of individual-level socioeconomic factors on racial disparities in cancer treatment and survival: findings from the National Longitudinal Mortality Study, 1979–2003. Cancer. 2011;117:3242–51.CrossRefPubMedPubMedCentral
15.
Albain KS, Unger JM, Crowley JJ, Coltman CA Jr, Hershman DL. Racial disparities in cancer survival among randomized clinical trials patients of the Southwest Oncology Group. J Natl Cancer Inst. 2009;101:984–92.CrossRefPubMedPubMedCentral
16.
Cristescu R, Lee J, Nebozhyn M, et al. Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes. Nat Med. 2015;21:449–56.CrossRefPubMed
17.
Hollstein M, Sidransky D, Vogelstein B, Harris CC. p53 mutations in human cancers. Science. 1991;253:49–53.CrossRefPubMed
18.
Hainaut P, Hollstein M. p53 and human cancer: the first ten thousand mutations. Adv Cancer Res. 2000;77:81–137.CrossRefPubMed
19.
Petitjean A, Achatz MI, Borresen-Dale AL, Hainaut P, Olivier M. TP53 mutations in human cancers: functional selection and impact on cancer prognosis and outcomes. Oncogene. 2007;26:2157–65.CrossRefPubMed
20.
Olivier M, Langerod A, Carrieri P, et al. The clinical value of somatic TP53 gene mutations in 1794 patients with breast cancer. Clin Cancer Res. 2006;12:157–1167.CrossRef
21.
Bergh J, Norberg T, Sjogren S, Lindgren A, Holmberg L. Complete sequencing of the p53 gene provides prognostic information in breast cancer patients, particularly in relation to adjuvant systemic therapy and radiotherapy. Nat Med. 1995;1:1029–34.CrossRefPubMed
22.
Aas T, Borresen AL, Geisler S, et al. Specific P53 mutations are associated with de novo resistance to doxorubicin in breast cancer patients. Nat Med. 1996;2:811–4.CrossRefPubMed
23.
Bull SB, Ozcelik H, Pinnaduwage D, et al. The combination of p53 mutation and neu/erbB-2 amplification is associated with poor survival in node-negative breast cancer. J Clin Oncol. 2004;22:86–96.CrossRefPubMed
24.
Kumar P, Aggarwal R. An overview of triple-negative breast cancer. Arch Gynecol Obstetr. 2016;293:247–69.CrossRef
25.
Papa A, Caruso D, Tomao S, Rossi L, Zaccarelli E, Tomao F. Triple-negative breast cancer: investigating potential molecular therapeutic target. Expert Opin Ther Targets. 2015;19:55–75.CrossRefPubMed
26.
Mathe A, Scott RJ, Avery-Kiejda KA. MiRNAs and other epigenetic changes as biomarkers in triple-negative breast cancer. Int J Mol Sci. 2015;16:28347–76.CrossRefPubMedPubMedCentral
27.
Turner N, Moretti E, Siclari O, et al. Targeting triple-negative breast cancer: is p53 the answer? Cancer Treat Rev. 2013;39:541–50.CrossRefPubMed
28.
Bertheau P, Espié M, Turpin E, et al. TP53 status and response to chemotherapy in breast cancer. Pathobiology. 2008;75:132–9.CrossRefPubMed
Metadata
Title
Rates of TP53 Mutation are Significantly Elevated in African American Patients with Gastric Cancer
Authors
Elke J. A. H. van Beek, MD
Jonathan M. Hernandez, MD
Debra A. Goldman, MS
Jeremy L. Davis, MD
Kaitlin McLaughlin, MD
R. Taylor Ripley, MD
Teresa S. Kim, MD
Laura H. Tang, MD, PhD
Jaclyn F. Hechtman, MD
Jian Zheng, MD
Marinela Capanu, PhD
Nikolaus Schultz, PhD
David M. Hyman, MD
Marc Ladanyi, MD
Michael F. Berger, PhD
David B. Solit, MD
Yelena Y. Janjigian, MD
Vivian E. Strong, MD, FACS
Publication date
01-07-2018
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 7/2018
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-018-6502-x

Other articles of this Issue 7/2018

Annals of Surgical Oncology 7/2018 Go to the issue

Health Services Research and Global Oncology

Will Palliative Care Ever Be Cool?

Gastrointestinal Oncology

The Negative Survival Impact of Infectious Complications After Surgery is Canceled Out by the Response of Neoadjuvant Chemotherapy in Patients with Esophageal Cancer

Colorectal Cancer

Salvage Abdominoperineal Resection for Squamous Cell Anal Cancer: A 30-Year Single-Institution Experience

Endocrine Tumors

Adjuvant Radiation is Associated with Improved Survival for Select Patients with Non-metastatic Adrenocortical Carcinoma

Health Services Research and Global Oncology

Changing the Status Quo, Including How We Measure It

Melanomas

The Effect of Temperature and Perfusion Time on Response, Toxicity, and Survival in Patients with In-transit Melanoma Metastases Treated with Isolated Limb Perfusion