Genomic profiling and the impact of MUC19 mutation in hepatoid adenocarcinoma of the stomach

Zhu, Min; Chen, Erbao; Yu, Shan; Chen, Xu; Yu, Yiyi; Cao, Xin; Li, Wei; Zhang, Pengfei; Wang, Yan; Lian, Baofeng; Zhang, Shuirong; Yan, Qiben; Huang, Lujia; Shi, Weiwei; Cui, Yuehong; Li, Qian; Liu, Tianshu

doi:10.1002/cac2.12336

Cited by 7 publications

(6 citation statements)

References 11 publications

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“…Kataoka et al 35 and Cho et al 36 found that ATBF1 mutations may mediate AFP expression and malignancy in GC. Liu et al discovered that MUC19 could upregulate AFP expression in GC cells and promote the development of hepatoid adenocarcinoma of the stomach (HAS) 37 . In this study, we found that DKK1 was associated with AFP expression in AFPGC by combining single‐cell and TCGA transcriptomic data, which was further confirmed by a DKK1 stimulation assay and immunohistochemistry of two other AFPGC patient slides.…”

Section: Discussionsupporting

confidence: 73%

“…Liu et al discovered that MUC19 could upregulate AFP expression in GC cells and promote the development of hepatoid adenocarcinoma of the stomach (HAS). 37 In this study, we found that DKK1 was associated with AFP expression in AFPGC by combining single-cell and TCGA transcriptomic data, which was further confirmed by a DKK1 stimulation assay and immunohistochemistry of two other AFPGC patient slides. Interestingly, GPC3 was also upregulated by DKK1 in vitro, accompanied by a decrease in ALB expression.…”

Section: Dkk1 Promotes Malignant Phenotype Of Afpgcsupporting

confidence: 69%

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Single‐cell characteristics and malignancy regulation of alpha‐fetoprotein‐producing gastric cancer

Mei

Wen

et al. 2023

Cancer Medicine

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Alpha-fetoprotein-producing gastric cancer (AFPGC) is a rare but highly malignant subtype of gastric cancer (GC) characterized by elevated serum alpha-fetoprotein (AFP) levels (>20 ng/mL). AFPGC accounts for 1.3%-15% of all GCs. 1 Patients with AFPGC have an aggressive clinical course, early occurrence of multiple organ metastases, primary multidrug resistance, and a poor prognosis. The 5-year survival rate of patients with stage IV AFPGC is 4.4%. 2 The pathogenesis of AFPGC is still not fully understood and effective therapeutic targets are lacking.In recent years, whole-exome sequencing (WES) has been used to study the genetic mutation profiles of AFPGC. In our previous study, we performed whole-exome sequencing of 29 cases of AFP-producing gastrointestinal cancer (AFPGI),

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Section: Discussionsupporting

confidence: 73%

Section: Dkk1 Promotes Malignant Phenotype Of Afpgcsupporting

confidence: 69%

Single‐cell characteristics and malignancy regulation of alpha‐fetoprotein‐producing gastric cancer

Mei

Wen

et al. 2023

Cancer Medicine

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“…The five most frequently mutated genes in 47 PDAC patients were KRAS (74.5%), TP53 (51.1%), SMAD4 (17%), ARID1A (12.8%), and CDKN2A (12.8%). Moreover, compared to data from the United States ( 25 ), the five most frequently mutated genes were KRAS (92%), TP53 (50%), SMAD4 (19%), FLG (10%), and ATXN1 (7%). Some genes (ARID1A, CDKN2A) in our cohort exhibited a higher mutation frequency.…”

Section: Discussionmentioning

confidence: 88%

Clinical and genetic characteristics in pancreatic cancer from Chinese patients revealed by whole exome sequencing

He,

Huang,

Tang

et al. 2023

Front. Oncol.

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BackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies worldwide, mostly as a result of the absence of early detection and specific treatment solutions. Consequently, identifying mutational profiles and molecular biomarkers is essential for increasing the viability of precision therapy for pancreatic cancer.MethodsWe collected blood and tumor tissue samples from 47 Chinese pancreatic cancer patients and used whole-exome sequencing (WES) to evaluate the genetic landscape.ResultsOur results showed the most frequently somatic alteration genes were KRAS (74.5%), TP53(51.1%), SMAD4 (17%), ARID1A (12.8%), CDKN2A (12.8%), TENM4 (10.6%), TTN (8.5%), RNF43(8.5%), FLG (8.5%) and GAS6 (6.4%) in Chinese PDAC patients. We also found that three deleterious germline mutations (ATM c.4852C>T/p. R1618*, WRN c.1105C>T/p. R369*, PALB2 c.2760dupA/p. Q921Tfs*7) and two novel fusions (BRCA1-RPRML, MIR943 (intergenic)-FGFR3). When compared to the Cancer Genome Atlas (TCGA) database, there is a greater mutation frequency of TENM4 (10.6% vs. 1.6%, p = 0.01), GAS6(6.4% vs. 0.5%, p = 0.035), MMP17(6.4% vs. 0.5%, p = 0.035), ITM2B (6.4% vs. 0.5%, p = 0.035) and USP7 (6.4% vs. 0.5%, p= 0.035) as well as a reduced mutation frequency of SMAD4 (17.0% vs. 31.5%, p = 0.075) and CDKN2A (12.8% vs. 47.3%, p < 0.001) were observed in the Chinese cohort. Among the 41 individuals examined for programmed cell death ligand 1(PD-L1) expression, 15 (36.6%) had positive PD-L1 expression. The median tumor mutational burden (TMB) was found to be 12muts (range, 0124). The TMB index was higher in patients with mutant-type KRAS MUT/TP53 MUT (p < 0.001), CDKN2A (p = 0.547), or SMAD4 (p = 0.064) compared to patients with wild-type KRAS/TP53, CDKN2A, or SMAD4.ConclusionsWe exhibited real-world genetic traits and new alterations in Chinese individuals with cancer of the pancreas, which might have interesting implications for future individualized therapy and medication development.

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“…Hepatoid adenocarcinoma of stomach (HAS) is a rare subtype of gastric cancer, accounting for 0.3–1% of all gastric cancer [ 1 , 2 ] with an incidence of about 0.58–0.83 cases per million people [ 3 ]. Though the incidence is relatively low, HAS has affected the whole treatment outcome of gastric cancer in view of its high malignancy and poor prognosis [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…Though the incidence is relatively low, HAS has affected the whole treatment outcome of gastric cancer in view of its high malignancy and poor prognosis [ 3 ]. Lymph node and liver metastasis are often present at diagnosis, which also results in less favorable therapeutic efficacy [ 1 ]. This tumor type has a unique hepatoid appearance of large polygonal eosinophilic neoplastic cells, similar immunohistochemistry (IHC) to hepatocellular carcinoma, and occasionally with elevated serum alpha fetoprotein (AFP) level [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical characteristics and potential therapeutic regimens of hepatoid adenocarcinoma of the stomach: a study of 139 cases

Yang,

Wu,

Wang

et al. 2023

The Journal of Pathology CR

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Hepatoid adenocarcinoma of stomach (HAS) is a special subtype of gastric cancer with poor prognosis. Immunohistochemical analysis could provide important clues for the treatment of HAS. A total of 159 patients were diagnosed as HAS and 139 were enrolled in this study. Statistical differences were determined using relative test methods and survival analyses were performed by the Kaplan–Meier method to find survival differences. All tumors in this study were negative for Epstein–Barr virus‐encoded small RNAs (EBERs) and almost all showed no loss of mismatch repair (MMR) proteins and were positive for alpha fetoprotein (AFP or spalt like transcription factor 4 (SALL4). About half of the tumors had a positive programmed death‐ligand 1 combined positive score (CPS) and 17.3% were positive for human epidermal growth factor receptor 2 (HER2). In addition, there was a relatively high proportion of cmet expression. We also found that HAS patients with recurrent disease treated by emerging therapy had a better survival than those treated with traditional chemotherapy (p = 0.002, median recurrence‐to‐death survival: 23 months versus 6 months); HAS patients who received anti‐HER2 therapy or harbored MMR deficiency had favorable prognosis. Overall, high proportions of MMR protein proficiency, positivity for AFP or SALL4, overexpression of HER2, CPS and cmet, as well as negative EBER findings, are distinctive characteristics of HAS patients. While negative EBER and MMR proficiency indicate molecular features of HAS, positivity for AFP or SALL4 could aid in the diagnosis of HAS. In addition, HAS patients could benefit from anti‐HER2 therapy, immunotherapy, and anti‐angiogenesis therapy.

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Genomic profiling and the impact of MUC19 mutation in hepatoid adenocarcinoma of the stomach

Cited by 7 publications

References 11 publications

Single‐cell characteristics and malignancy regulation of alpha‐fetoprotein‐producing gastric cancer

Single‐cell characteristics and malignancy regulation of alpha‐fetoprotein‐producing gastric cancer

Clinical and genetic characteristics in pancreatic cancer from Chinese patients revealed by whole exome sequencing

Immunohistochemical characteristics and potential therapeutic regimens of hepatoid adenocarcinoma of the stomach: a study of 139 cases

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