Accumulated genetic mutations leading to accelerated initiation and progression of colorectal cancer in a patient with Gardner syndrome: A case report.

Rationale Gardner syndrome is a rare autosomal dominant disorder with a high degree of penetrance, which is characterized by intestinal polyposis, osteomas, and dental abnormalities. Majority of patients with Gardner syndrome will develop colorectal cancer by the age of 40 to 50 years. Mutations in the adenomatous polyposis coli gene are supposed to be responsible for the initiation of Gardner syndrome. Patient concerns A 22-year-old Chinese female was admitted to our hospital due to abdominal pain and bloody stool. Diagnosis The patient presented with multiple intestinal polyposis, desmoid tumors, and dental abnormalities was diagnosed as Gardner syndrome and further examination revealed a colon tumor. Interventions and outcomes Patients were implanted with stents to alleviate bowel obstruction, and were treated with oxaliplatin combined with 5-Fu for 4 cycles, but the efficacy was not good. We performed next generation sequencing of 390 genes for the tumor specimens. We detected adenomatous polyposis coli E1538Ifs∗5, KRAS G12D, NF1 R652C, loss of SMAD4, TP53 R175H, IRF2 p.R82S, TCF7L2 p.A418Tfs∗14, and SMAD4 p.L43F in this patient. Lessons We reported serial mutations in key genes responsible for initiation and progression of colorectal cancer from a patient with Gardner syndrome.