Hereditary Gastric Cancer Syndromes

Colvin, Hugh; Yamamoto, Ken; Wada, Noriko; Mori, Masaki

doi:10.1016/j.soc.2015.06.002

Cited by 30 publications

(36 citation statements)

References 68 publications

(78 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These include hereditary diffuse gastric cancer syndrome (HDGC), familial adenomatous polyposis, gastric adenocarcinoma and proximal polyposis of the stomach, Li-Fraumeni syndrome, Lynch syndrome, juvenile-polyposis syndrome, and Peutz-Jeghers syndrome [1]. Although individuals with personal or family cancer history consistent with one of the above syndromes are currently recommended to receive genetic cancer risk assessment and genetic testing, only a minority of gastric cancer patients are affected by these known hereditary syndromes [1, 2]. …”

Section: Introductionmentioning

confidence: 99%

Genetic Gastric Cancer Susceptibility in the International Clinical Cancer Genomics Community Research Network

et al. 2017

View full text Add to dashboard Cite

Few susceptibility genes for gastric cancer have been identified. We sought to identify germline susceptibility genes from participants with gastric cancer from an international hereditary cancer research network. Adults with gastric cancer of any histology, and with a germline DNA sample (n= 51), were retrospectively selected. For those without previously identified germline mutations (n= 43), sequencing was performed for 706 candidate genes. Twenty pathogenic or likely pathogenic variants were identified among 18 participants. Eight of the 18 participants had previous positive clinical testing, including six with CDH1 pathogenic or likely pathogenic variants, and two with pathogenic MSH2 and TP53 variants. Of the remaining 10, six were in BRCA1 DNA damage response pathway genes (ATM, ATR, BRCA2, BRIP1, FANCC, TP53), other variants were identified in CTNNA1, FLCN, SBDS, and GNAS. Participants identified with pathogenic or likely pathogenic variants were younger at gastric cancer diagnosis than those without, 39.1 versus 48.0 years, and over 50% had a close family member with gastric cancer (p-values <0.0001). In conclusion, many participants were identified with mutations in clinically-actionable genes. Age of onset and family history of gastric cancer were mutation status predictors. Our findings support multigene panels in identifying gastric cancer predisposition.

show abstract

Section: Introductionmentioning

confidence: 99%

Genetic Gastric Cancer Susceptibility in the International Clinical Cancer Genomics Community Research Network

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Germline mutations in some driver genes determine predisposition to the development of hereditary gastric cancer. Mutations in CDH1 are responsible for the development of early hereditary diffuse GC, as are mutations in TP53 (Li-Fraumeni syndrome), STK11 (Peutz-Jeghers syndrome), SMAD4 or BMPR1A (gastrointestinal polyposis) and PTEN (Cowden syndrome) 6 . Thus, it is advisable to combine the BMPR1A, SMAD4, CDH1, TP53, STK11 and PTEN genes into a targeted sequencing panel that will provide significant information on the mutational profile of gastric tumours in both hereditary and sporadic cancer, which can be associated with the clinical and pathomorphological features of the disease.…”

mentioning

confidence: 99%

Clinical relevance of somatic mutations in main driver genes detected in gastric cancer patients by next-generation DNA sequencing

Nemtsova

Калинкин

Kuznetsova

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Somatic mutation profiling in gastric cancer (GC) enables main driver mutations to be identified and their clinical and prognostic value to be evaluated. We investigated 77 tumour samples of GC by next-generation sequencing (NGS) with the Ion AmpliSeq Hotspot Panel v2 and a custom panel covering six hereditary gastric cancer predisposition genes (BMPR1A, SMAD4, CDH1, TP53, STK11 and PTEN). Overall, 47 somatic mutations in 14 genes were detected; 22 of these mutations were novel. Mutations were detected most frequently in the CDH1 (13/47) and TP53 (12/47) genes. As expected, somatic CDH1 mutations were positively correlated with distant metastases (p = 0.019) and tumours with signet ring cells (p = 0.043). These findings confirm the association of the CDH1 mutations with diffuse GC type. TP53 mutations were found to be significantly associated with a decrease in overall survival in patients with Lauren diffuse-type tumours (p = 0.0085), T3-T4 tumours (p = 0.037), and stage III-IV tumours (p = 0.013). Our results confirm that the detection of mutations in the main driver genes may have a significant prognostic value for GC patients and provide an independent GC-related set of clinical and molecular genetic data.Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide after lung cancer and breast cancer. The incidence of GC is particularly high in East Asia, including China, Japan and Korea, and in South America 1 . Based on the Lauren classification, GC is divided into two main types, namely, intestinal and diffuse, which have different epidemiological, morphological and clinical features. Intestinal GC commonly appears in elderly patients with multifocal atrophic gastritis, which is accompanied by intestinal metaplasia or dysplasia. Diffuse GC is more common in younger patients, and its association with atrophic gastritis or intestinal metaplasia is not obvious. Clinical differences between these two types reflect different mechanisms of the development and molecular pathogenesis of tumours 2 . However, Lauren's classification is not closely associated with treatment and prognosis, necessitating the development of a classification combining clinical, morphological, and molecular features of GC in response to certain therapeutic modalities.Comprehensive studies, including analyses of the genome, epigenome, proteome and transcriptome, offered an entirely different view on the tumour, moving it out of a single plane and into a multidimensional spatial image. The ability to determine the tumour-specific spectrum of genetic and epigenetic changes enables us to expand our understanding of the molecular pathogenesis of the tumour and to obtain information about the potential of targeted therapies. Mutational profiling is one way to classify tumours depending on the mutation spectrum into specific molecular subtypes that differ from the standard morphological classification. The results of recent studies, such as TCGA Validation of mutations detected by next-generation sequencing. Validation of th...

show abstract

“…Independent of epidemiologic trends is a population of patients with hereditary gastric cancer syndromes (24,25). Recent improvement in molecular genetics has refined our understanding of the mutations causing hereditary gastric cancer (26).…”

Section: Hereditary Gastric Cancermentioning

confidence: 99%

Contemporary paradigm for the evaluation and treatment of hereditary gastric cancer

Skill

Maluccio

2019

Transl. Gastroenterol. Hepatol

View full text Add to dashboard Cite

Gastric cancer is the third leading cause of cancer mortality worldwide. Survival is linked to stage at diagnosis and tolerance to surgery and adjuvant therapy. The emergence of sophisticated methods to identify patients at high risk for the development of gastric cancer has given us an opportunity to eliminate a lethal disease in an identifiable patient population. Guidelines and recommendations have been established and prophylactic total gastrectomy is considered the most effective treatment. However, this requires substantial physical and emotional investment. It is imperative that patients and families are supported by genetic counseling, ongoing surveillance, and survivorship studies.

show abstract

Hereditary Gastric Cancer Syndromes

Cited by 30 publications

References 68 publications

Genetic Gastric Cancer Susceptibility in the International Clinical Cancer Genomics Community Research Network

Genetic Gastric Cancer Susceptibility in the International Clinical Cancer Genomics Community Research Network

Clinical relevance of somatic mutations in main driver genes detected in gastric cancer patients by next-generation DNA sequencing

Contemporary paradigm for the evaluation and treatment of hereditary gastric cancer

Contact Info

Product

Resources

About