Gastric Cancer in &lt;b&gt;&lt;i&gt;BRCA1&lt;/i&gt;&lt;/b&gt; Germline Mutation Carriers: Results of Endoscopic Screening and Molecular Analysis of Tumor Tissues

Avanesyan, Albina A; Sokolenko, Anna P.; Ivantsov, Alexandr O.; Клещев, М. А.; Maydin, Mikhail; Bizin, Ilya V.; Shelekhova, Ksenya V.; Gorodnova, Tatiana V.; Bessonov, Alexandr A.; Anisimova, E.; Volynshchikova, O. A.; Romanko, Alexandr A.; Ni, V.; Broyde, Robert V; Tkachenko, Oleg B.; Whitehead, Aldon J.; Scherbakov, Alexandr M; Imyanitov, Evgeny N.

doi:10.1159/000511323

Cited by 9 publications

(7 citation statements)

References 27 publications

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“…However, we identified an ERBB2 mutation at V842I, which is commonly found in colorectal cancer[ 21 ].We discovered that 15 patients carried BRCA1/2 mutations. The current study also demonstrated that GC or GEJ tumour patients carried BRCA1/2 mutations[ 22 ], which may be related to tumorigenesis, including GC development. A molecular analysis of BRCA1/2 mutations clearly revealed distinct categories of tumours[ 23 ].…”

Section: Discussionmentioning

confidence: 64%

Detection of a novel panel of 24 genes with high frequencies of mutation in gastric cancer based on next-generation sequencing

Yang¹,

Qiu²,

Bashir³

et al. 2022

WJCC

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BACKGROUND Gastric cancer is a leading cause of cancer-related mortality worldwide. Many somatic mutations have been identified based on next-generation sequencing; they likely play a vital role in cancer treatment selection. However, next-generation sequencing has not been widely used to diagnose and treat gastric cancer in the clinic. AIM To test the mutant gene frequency as a guide for molecular diagnosis and personalized therapy in gastric cancer by use of next-generation sequencing. METHODS We constructed a panel of 24 mutant genes to detect somatic nucleotide variations and copy number variations based on a next-generation sequencing technique. Our custom panel included high-mutation frequency cancer driver and tumour suppressor genes. Mutated genes were also analyzed using the cBioPortal database. The clinical annotation of important variant mutation sites was evaluated in the ClinVar database. We searched for candidate drugs for targeted therapy and immunotherapy from the OncoKB database. RESULTS In our study, the top 16 frequently mutated genes were TP53(58%), ERBB2(28%), BRCA2 (23%), NF1 (19%), PIK3CA (14%), ATR (14%), MSH2 (12%), FBXW7 (12%), BMPR1A (12%), ERBB3 (11%), ATM (9%), FGFR2 (8%), MET (8%), PTEN (6%), CHD4 (6%), and KRAS (5%). TP53 is a commonly mutated gene in gastric cancer and has a similar frequency to that in the cBioPortal database. 33 gastric cancer patients (51.6%) with microsatellite stability and eight patients (12.5%) with microsatellite instability-high were investigated. Enrichment analyses demonstrated that high-frequency mutated genes had transmembrane receptor protein kinase activity. We discovered that BRCA2, PIK3CA, and FGFR2 gene mutations represent promising biomarkers in gastric cancer. CONCLUSION We developed a powerful panel of 24 genes with high frequencies of mutation that could detect common somatic mutations. The observed mutations provide potential targets for the clinical treatment of gastric cancer.

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Section: Discussionmentioning

confidence: 64%

Detection of a novel panel of 24 genes with high frequencies of mutation in gastric cancer based on next-generation sequencing

Yang¹,

Qiu²,

Bashir³

et al. 2022

WJCC

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“…The colonized biotin-type DNA probe (GeneSeqOne TM ) was used to hybridize and capture 415 coding regions of genes related to gastric cancer and 16 introns of genes in the library. Meanwhile, the library DNA was amplified with the help of Illumina p5, p7 primers, and KAPA HiFi HotStart ReadyMix (Sigma-Aldrich, Shanghai, China), and the enriched library was sequenced on the HiSeq 4000 platform using a 2×150 bp sequencing kit [ 10 ]. (4) Sequencing data processing: Trimmomatic 25 software was used to filter the sequencing data and remove low-quality bases or N bases.…”

Section: Methodsmentioning

confidence: 99%

Analysis of Threshold Changes of Tumor Mutation Burden of Gastric Cancer and Its Relationship with Patients’ Prognosis

Zhang

et al. 2021

Journal of Oncology

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Objective. Gastric cancer is a malignant tumor originating from gastric mucosal epithelium. Here, we aimed to investigate the analysis of the threshold change of gastric cancer tumor mutation burden (TMB) and its relationship with the prognosis of patients. Methods. 256 patients with gastric cancer were selected as subjects. All patients were in the advanced stage and received surgical resection of D2 lymph node dissection. After the operation, a follow-up was performed for 24 months, and the disease-free survival and overall survival of patients were counted. The NGS molecular biological was detected to obtain gastric cancer tumor mutation burden (TMB) data. Pearson correlation analysis software was used to analyze the correlation between TMB threshold and disease-free survival or overall survival of patients with gastric cancer, and the multivariate logistic analysis was performed as well. Results. The disease-free survival period and the overall survival period of patients in the low-to-medium TMB group were both longer than those in the high TMB group. Pearson correlation analysis results showed that the TMB threshold was negatively correlated with the disease-free survival and overall survival of gastric cancer patients. Results from multivariate logistic analysis showed that high TMB thresholds have a greater impact on disease-free survival and overall survival of patients, but the impact of medium and low TMB thresholds on disease-free survival and overall survival of patients is weakened. Conclusions. The TMB threshold level has a predictive effect on the effect of surgical resection of D2 lymph node dissection, and high levels of TMB can significantly affect disease-free survival and overall survival of patients with advanced gastric cancer.

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“…The most frequent cause of this chromosomal instability is a biallelic inactivation of BRCA1/2 genes in hereditary cancers [88][89][90]. BRCA1 and BRCA2 germ-line mutations predispose to breast, ovarian and possibly stomach malignancies [88,90,91]. In addition, BRCA2 pathogenic alleles are associated with increased risk of prostate and pancreatic carcinomas [92,93].…”

Section: Integrative Testsmentioning

confidence: 99%

Cancer Therapy Guided by Mutation Tests: Current Status and Perspectives

Aleksakhina

Imyanitov

2021

IJMS

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The administration of many cancer drugs is tailored to genetic tests. Some genomic events, e.g., alterations of EGFR or BRAF oncogenes, result in the conformational change of the corresponding proteins and call for the use of mutation-specific compounds. Other genetic perturbations, e.g., HER2 amplifications, ALK translocations or MET exon 14 skipping mutations, cause overproduction of the entire protein or its kinase domain. There are multilocus assays that provide integrative characteristics of the tumor genome, such as the analysis of tumor mutation burden or deficiency of DNA repair. Treatment planning for non-small cell lung cancer requires testing for EGFR, ALK, ROS1, BRAF, MET, RET and KRAS gene alterations. Colorectal cancer patients need to undergo KRAS, NRAS, BRAF, HER2 and microsatellite instability analysis. The genomic examination of breast cancer includes testing for HER2 amplification and PIK3CA activation. Melanomas are currently subjected to BRAF and, in some instances, KIT genetic analysis. Predictive DNA assays have also been developed for thyroid cancers, cholangiocarcinomas and urinary bladder tumors. There is an increasing utilization of agnostic testing which involves the analysis of all potentially actionable genes across all tumor types. The invention of genomically tailored treatment has resulted in a spectacular improvement in disease outcomes for a significant portion of cancer patients.

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Gastric Cancer in <b><i>BRCA1</i></b> Germline Mutation Carriers: Results of Endoscopic Screening and Molecular Analysis of Tumor Tissues

Cited by 9 publications

References 27 publications

Detection of a novel panel of 24 genes with high frequencies of mutation in gastric cancer based on next-generation sequencing

Detection of a novel panel of 24 genes with high frequencies of mutation in gastric cancer based on next-generation sequencing

Analysis of Threshold Changes of Tumor Mutation Burden of Gastric Cancer and Its Relationship with Patients’ Prognosis

Cancer Therapy Guided by Mutation Tests: Current Status and Perspectives

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