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

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

doi:10.1245/s10434-018-6502-x

Cited by 22 publications

(18 citation statements)

References 24 publications

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“…In this study, we sought to gain a deeper understanding of the molecular features of gastric cancer in the AN population. Our analysis of a targeted 50 somatic gene mutation panel confirmed 60.6% of the patients had one or more gene mutations with the TP53 gene being the most frequently altered among AN patients, which was similar but lower in frequency, 36% when compared to other populations, 46-49% [13,[22][23][24]. Other genes that were commonly mutated in AN gastric cancer patients were PIK3CA, PTEN, KRAS, APC, and CTNN1B, which were comparable to the TCGA study (Table 3) [13].…”

Section: Discussionmentioning

confidence: 56%

Molecular Classification of Gastric Cancer among Alaska Native People

Martinson

Mallari

Richter

et al. 2020

Cancers

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Gastric cancer is an aggressive and heterogeneous malignancy that often varies in presentation and disease among racial and ethnic groups. The Alaska Native (AN) people have the highest incidence and mortality rates of gastric cancer in North America. This study examines molecular markers in solid tumor samples from eighty-five AN gastric adenocarcinoma patients using next-generation sequencing, immunohistochemistry, and in situ hybridization analysis. AN patients have a low mutation burden with fewer somatic gene mutations in their tumors compared to other populations, with the most common mutation being TP53. Epstein-Barr virus (EBV) was associated with 20% of AN gastric cancers, which is higher than the world average of 10%. The inflammation marker, cyclooxygenase-2 (COX-2), is highly expressed in patients with the lowest survival rates. Mismatch repair deficiency was present in 10% of AN patients and was associated with patients who were female, 50 years or older, gene mutations, and tumors in the distal stomach. Program death-ligand 1 (PD-L1) was expressed in 14% of AN patients who were more likely to have MMR deficiency, EBV-associated gastric cancers, and mutations in the PIK3CA gene, all of which have been linked to clinical response to PD-1 inhibitors. These studies suggest a portion of AN gastric cancer patients could be candidates for immunotherapy. Overall, this study highlights future avenues of investigation for clinical and translational studies, so that we can improve early detection and develop more effective treatments for AN patients.

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Section: Discussionmentioning

confidence: 56%

Molecular Classification of Gastric Cancer among Alaska Native People

Martinson

Mallari

Richter

et al. 2020

Cancers

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“…Poor outcomes could be attributed to environmental and genetic factors. It has been reported that AA patients tend to have higher rates of TP53 mutation, a universally accepted aggressive tumor marker, attributing to about 89% patients, in comparison to 40% in the Caucasian population [23]. Other contributing factors could be high prevalence of Helicobacter pylori infections seen in AA, and presentation at an older age [16,[24][25][26].…”

Section: Discussionmentioning

confidence: 99%

Socio-Demographic Disparities in Gastric Adenocarcinoma: A Population-Based Study

Rana

Gosain

Lemini

et al. 2020

Cancers

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Background: Gastric cancer is one of the leading causes of cancer-related mortality worldwide, accounting for 8.2% of cancer-related deaths. The purpose of this study was to investigate the geographic and sociodemographic disparities in gastric adenocarcinoma patients. Methods: We conducted a retrospective study in gastric adenocarcinoma patients between 2004 and 2013. Data were obtained from the National Cancer Data Base (NCDB). Univariate and multivariable analyses were performed to evaluate overall survival (OS). Socio-demographic factors, including the location of residence [metro area (MA) or rural area (RA)], gender, race, insurance status, and marital status, were analyzed. Results: A total of 88,246 [RA, N = 12,365; MA, N = 75,881] patients were included. Univariate and multivariable analysis showed that RA had worse OS (univariate HR = 1.08, p < 0.01; multivariate HR = 1.04; p < 0.01) compared to MA. When comparing different racial backgrounds, Native American and African American populations had poorer OS when compared to the white population; however, Asian patients had a better OS (multivariable HR = 0.68, p < 0.01). From a quality of care standpoint, MA patients had fewer median days to surgery (28 vs. 33; p < 0.01) with fewer positive margins (6.3% vs. 6.9%; p < 0.01) when compared to RA patients. When comparing the extent of lymph node dissection, 19.6% of MA patients underwent an extensive dissection (more than or equal to 15 lymph nodes) in comparison to 18.7% patients in RA (p = 0.03). Discussion: This study identifies socio-demographic disparities in gastric adenocarcinoma. Future health policy initiatives should focus on equitable allocation of resources to improve the outcomes.

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“…In previously published studies, the presence of TP53 gene mutation was not proved to be an independent prognostic factor for patients with advanced GCs[ 1 , 12 ], or it was correlated with a shorter survival[ 13 , 14 ]. Our study confirmed the longer survival of wt cases, compared to those with TP53 gene mutation, especially in patients without lymph node metastases.…”

Section: Discussionmentioning

confidence: 99%

“…The TP53 mutation rate was proved to be dependent by various parameters, including geographic characteristics known to be induced by interactions between Helicobacter pylori infection and other environmental, molecular and genetic factors[ 13 , 15 , 16 ]. In our study, which included Romanian patients, the mutation rate was 33.83%, similar to American Caucasian (40%) and Hispanic patients (43%), whereas Asian and African American patients, similar to patients in Bangladesh, proved to have significantly elevated mutations rates of 56%, 89%, and 73%, respectively[ 16 , 17 ].…”

Section: Discussionmentioning

confidence: 99%

Maspin subcellular expression in wild-type and mutant TP53 gastric cancers

Gurzu¹,

Jung²,

Sugimura³

et al. 2020

WJGO

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BACKGROUND Although the role of p53 in the evolution and prognosis of gastric cancer (GC) has been extensively examined, the exact mechanism of action is incompletely understood. In the last years, p53-target genes were supposed to be involved in the p53 pathway. One of them is the tumor-suppressor gene Maspin, which codifies the protein with the same name. Maspin activity depends on its subcellular localization. To our knowledge, the possible role of TP53 gene in Maspin subcellular localization, in GC cells, has not yet been studied in a large number of human samples. AIM To evaluate the possible role of wild-type and mutated p53 in Maspin subcellular localization. METHODS The present study included 266 consecutive patients with GC in which TP53 gene status, and mutations in exons 2 to 11, respectively, were analyzed and correlated with immunohistochemical expression of p53 and Maspin. RESULTS None of the 266 cases showed mutations in exon 9. The rate of TP53 mutations was 33.83%. The mutation rate was slightly higher in distally-located GCs, with a lower degree (≤ 5 buds/ high power fields) of dyscohesivity ( P < 0.01). The wild-type cases had a longer survival, compared with mutant GCs, especially in patients without lymph node metastases, despite the high depth of tumor infiltration ( P = 0.01). The Dukes-MAC-like staging system was proved to have the most significant independent prognostic value ( P < 0.01). The statistical correlations proved that TP53 gene mutations in exon 7 might induce knockdown of Maspin, but wild-type p53 can partially restore nuclear Maspin expression and decrease the metastatic potential of gastric adenocarcinoma cells. CONCLUSION Downregulated Maspin might be induced by mutations in exon 7 of the TP53 gene but wild-type p53 can partially restore nuclear Maspin expression. These findings should be proved in experimental studies.

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

Abstract: 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.

Cited by 22 publications

References 24 publications

Molecular Classification of Gastric Cancer among Alaska Native People

Molecular Classification of Gastric Cancer among Alaska Native People

Socio-Demographic Disparities in Gastric Adenocarcinoma: A Population-Based Study

Maspin subcellular expression in wild-type and mutant TP53 gastric cancers

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