Hereditary diffuse gastric cancer is an autosomal dominant syndrome associated with truncating mutations of the CDH1 gene. This mutation results in ineffective E-cadherin expression, a protein implicated in maintaining cellular adhesion, thereby facilitating metastatic tumor invasion.

Clinically manifests as early-onset diffuse gastric cancer (<40 years of age); family history of diffuse gastric cancer, lobular breast cancer, and signet ring cell colon cancer.

Prophylactic gastrectomy is recommended.

Suggested Readings:

Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.

DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.

P53, RB1, BRCA1, and CDH1 are examples of tumor suppressor genes.

Mutations, deletions, or silencing in tumor suppressor genes result in loss of function which may drive oncogenesis.

Suggested Readings:

Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.

DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.

With regard to immune effector cell response: LAG3, TIM3, PDL1, and BTLA are examples of inhibitory molecules.

Effective T-cell activation is dependent on the CD3 transduction and additional stimulatory or inhibitory signals.

Suggested Readings:

Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.

DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.

Heredity Syndrome: Li-Fraumeni syndrome (LFS)

LFS is an autosomal dominant disorder implicated in patients with a strong family history of breast cancer, sarcoma, brain tumors, adrenocortical carcinoma, and leukemia.