Hereditary Gastric Cancer Syndromes: An Integrated Genomic and Clinicopathologic Study of the Predisposition to Gastric Cancer

Gastric cancers are cancers of the stomach. Hereditary cancers are passed from parent to child. Researchers want to gather data about hereditary gastric cancers. Bulk RNA sequencing (RNA-seq) of signet ring cells (SRCs) and adjacent non-SRC epithelium (NEP) was performed on laser-capture microdissected (LCM) regions of interest found in risk-reducing total gastrectomy specimens from hereditary diffuse gastric cancer (HDGC) patients (Clinicaltrials.gov ID: NCT03030404). Twenty patients (6 male, 14 female) with confirmed HDGC were identified. Analysis of differentially expressed genes (DEGs) demonstrated upregulation of certain individual epithelial–mesenchymal transition (EMT) and proliferation genes. SRC regions had significant enrichment in pathways involved in T cell signaling. CIBERSORTx predicted significant increases in the presence of regulatory T cells (Tregs) specific to SRC regions. ]]>
Inclusion Criteria: Individuals or their family members with any of the following: Fulfills clinical criteria for Hereditary Diffuse Gastric Cancer (HGDC) syndrome or Gastric Adenocarcinoma and Proximal Polyposis of the Stomach (GAPPS) syndrome. Clinically suspicious personal or family medical history of gastric cancer or gastric cancer syndrome that warrants genetics evaluation. Current diagnosis of gastric cancer and a germline mutation associated with a known cancer syndrome or an associated family history of gastric cancer. Harbors a pathogenic germline mutation known to predispose to gastric cancer. First-degree relatives, regardless of family history or personal history of cancer, with a documented deleterious germline mutation, including but not limited to CDH1, CTNNA1, and SDH complex genes (including SDHA, SDHB, SDHC, SDHD) , known to predispose to gastric tumors. Diagnosis or suspicion of a premalignant or malignant stomach lesion of suspected hereditary etiology. Age at 2 years or older. Note: Patients under 18 years of age may only participate in research sample collection if the tissue acquisition is performed during a clinically indicated surgical procedure, and the sampling of tissue, blood, saliva or urine collection does not add risk to the clinically indicated procedures. Ability of subject or legally authorized representative (LAR) to understand and the willingness to sign a written informed consent document. ]]>