The impact of recent next generation sequencing and the need for a new classification in gastric cancer

Businello, Gianluca; Galuppini, Francesca; Fassan, Matteo

doi:10.1016/j.bpg.2021.101730

Cited by 18 publications

(17 citation statements)

References 108 publications

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“…Therefore, they are only applicable in a limited manner to the formalin fixed, paraffin embedded tumor tissue usually available in clinical practice. Second, although both classifications define four molecular subtypes of GAC, these subtypes only show a partial overlap, resulting in uncertainty, as a flawless, unifying classification is still lacking [26][27][28].…”

Section: Discussionmentioning

confidence: 99%

Combined Simplified Molecular Classification of Gastric Adenocarcinoma, Enhanced by Lymph Node Status: An Integrative Approach

Daun

Nienhold

Paasinen-Sohns

et al. 2021

Cancers

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Gastric adenocarcinoma (GAC) is a heterogeneous disease and at least two major studies have recently provided a molecular classification for this tumor: The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ARCG). Both classifications quote four molecular subtypes, but these subtypes only partially overlap. In addition, the classifications are based on complex and cost-intensive technologies, which are hardly feasible for everyday practice. Therefore, simplified approaches using immunohistochemistry (IHC), in situ hybridization (ISH) as well as commercially available next generation sequencing (NGS) have been considered for routine use. In the present study, we screened 115 GAC by IHC for p53, MutL Homolog 1 (MLH1) and E-cadherin and performed ISH for Epstein–Barr virus (EBV). In addition, sequencing by NGS for TP53 and tumor associated genes was performed. With this approach, we were able to define five subtypes of GAC: (1) Microsatellite Instable (MSI), (2) EBV-associated, (3) Epithelial Mesenchymal Transition (EMT)-like, (4) p53 aberrant tumors surrogating for chromosomal instability and (5) p53 proficient tumors surrogating for genomics stable cancers. Furthermore, by considering lymph node metastasis in the p53 aberrant GAC, a better prognostic stratification was achieved which finally allowed us to separate the GAC highly significant in a group with poor and good-to-intermediate prognosis, respectively. Our data show that molecular classification of GAC can be achieved by using commercially available assays including IHC, ISH and NGS. Furthermore, we present an integrative workflow, which has the potential to overcome the uncertainty resulting from discrepancies from existing classification schemes.

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Section: Discussionmentioning

confidence: 99%

Combined Simplified Molecular Classification of Gastric Adenocarcinoma, Enhanced by Lymph Node Status: An Integrative Approach

Daun

Nienhold

Paasinen-Sohns

et al. 2021

Cancers

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“…First line chemotherapy for patients with metastatic disease consists most commonly of a combination of platinum compounds and fluoropyrimidine, which has only limited efficacy and the majority of patients experience disease progression. Recent advances are now permitting molecular characterisation of these tumours (reviewed in [ 5 ]), and clinical trials in appropriately selected patients investigating the use of combined chemotherapy with immunotherapy using inhibitors of HER2 [ 6 ] and PDL-1, for example have shown significant improvements in disease free survival. As a result, these are now recommended as standard of care [ 7 ].…”

Section: The Need To Understand the Complex Factors That Lead To Gast...mentioning

confidence: 99%

Homeostasis and Cancer Initiation: Organoids as Models to Study the Initiation of Gastric Cancer

Idowu

Bertrand

Walduck

2022

IJMS

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Gastric cancer represents a significant disease burden worldwide. The factors that initiate cancer are not well understood. Chronic inflammation such as that triggered by H. pylori infection is the most significant cause of gastric cancer. In recent years, organoid cultures developed from human and animal adult stem cells have facilitated great advances in our understanding of gastric homeostasis. Organoid models are now being exploited to investigate the role of host genetics and bacterial factors on proliferation and DNA damage in gastric stem cells. The impact of a chronic inflammatory state on gastric stem cells and the stroma has been less well addressed. This review discusses what we have learned from the use of organoid models to investigate cancer initiation, and highlights questions on the contribution of the microbiota, chronic inflammatory milieu, and stromal cells that can now be addressed by more complex coculture models.

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“…The goal of this research was to develop a prognostic model for GC patients using genes linked to lipid metabolism [ 9 ]. Epigenetic and genetic mechanisms in esophageal cancer cells were studied by researchers [ 10 ]. The molecular landscape of gastric cancer has improved thanks to the use of next-generation sequencing (NGS), and new classification methods for molecular heterogeneity have been proposed.…”

Section: Related Workmentioning

confidence: 99%

Analysis of Influencing Factors on the Occurrence and Development of Gastric Cancer in High-Incidence Areas of Digestive Tract Tumors Based on High Methylation of GPX3 Gene

Xie

Jian-min

2022

Journal of Oncology

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Stomach cancer is the second largest cause of cancer-related mortality globally, and it continues to be a reason for worry today. Inhalation of the stomach cancer risk factor H. pylori produces large levels of reactive oxygen species (ROS). When combined with glutathione reductase, glutathione peroxidase 3 (GPX3) catalyzes the reduction of hydrogen peroxide and lipid peroxides. To get a better understanding of the GPX3 gene’s role in the illness, the researchers used quantitative real-time RT-PCR to examine the gene’s expression and regulation in gastric cancer cell lines, original gastric cancer samples, and 45 normal stomach mucosa adjacent to malignancies. According to the research, GPX3 expression was decreased or silenced in eight of nine cancer cell lines and 83 percent of gastric cancer samples (90/108) as compared to normal gastric tissues in the vicinity of the tumor ( P < 0.0001 ). It was found that 60 percent of stomach cancer samples exhibited DNA hypermethylation after analyzing the GPX3 promoter ( P = 0.007 ) (a methylation level of more than 10 percent, as measured by bisulfite pyrosequencing). In stomach tumors, we found a statistically significant reduction in the amount of GPX3 DNA copies ( P < 0.001 ). The gene expression of SNU1 and MKN28 cells was restored after treatment with 5-Aza-2′ Deoxycytidine to reduce GPX3 promoter methylation. Genetic and epigenetic alterations lead GPX3 to be dysfunctional in gastric cancer. This indicates that the systems that regulate ROS have been disrupted, and GPX3 may be implicated in the development of gastric cancer, as shown by our results when evaluated alone and in combination.

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The impact of recent next generation sequencing and the need for a new classification in gastric cancer

Cited by 18 publications

References 108 publications

Combined Simplified Molecular Classification of Gastric Adenocarcinoma, Enhanced by Lymph Node Status: An Integrative Approach

Combined Simplified Molecular Classification of Gastric Adenocarcinoma, Enhanced by Lymph Node Status: An Integrative Approach

Homeostasis and Cancer Initiation: Organoids as Models to Study the Initiation of Gastric Cancer

Analysis of Influencing Factors on the Occurrence and Development of Gastric Cancer in High-Incidence Areas of Digestive Tract Tumors Based on High Methylation of GPX3 Gene

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