APC mosaicism in a young woman with desmoid type fibromatosis and familial adenomatous polyposis

Astrid Tenden Stormorken,Kristin Aaberg,Toto Hølmebakk,Ole-Jacob Norum,Sonja E Steigen,Eli Marie Grindedal,Thomas Berg

doi:10.1007/s10689-018-0072-8

Abstract

Familial adenomatous polyposis (FAP) is usually caused by germline mutations in the adenomatous polyposis coli (APC) gene. The classic form is characterized by hundreds to thousands of adenomas in the colorectum and early onset colorectal cancer (CRC) if left untreated. FAP is also associated with multiple extra-colonic manifestations such as gastroduodenal polyps, osteomas, epidermoid cysts, fibromas and desmoids. Most desmoid tumours in FAP patients occur intra-abdominally. Approximately 15–20% of the APC mutations are de novo mutations. Somatic mosaicism has been reported in some sporadic cases of polyposis but is probably an underestimated cause of the disease. This case report presents the detection of a mosaic APC mutation in a 26-year-old woman who as a child had been diagnosed with desmoid type fibromatosis. FAP was suggested when she presented with extensive extra abdominal fibromatosis. Our findings indicate that APC mutations may be suspected in patients presenting with a desmoid regardless of its location. If there is clinical evidence that the patient has FAP, adenomas and colonic mucosa in addition to leukocyte DNA should be included in the screening, preferably using methods that are more sensitive than Sanger sequencing.

Highlights

Familial adenomatous polyposis (FAP) is a rare autosomal dominant disorder caused by mutations in the Adenomatous Polyposis Coli (APC) gene
FAP is associated with extra-gastrointestinal manifestations such as dental abnormalities, osteomas and soft tissue tumours like epidermoid cysts, Gardner fibromas and desmoid tumours [7]
Our case illustrates that FAP may be suspected in patients with only extraabdominal desmoids, and that colonoscopy and genetic testing of the APC gene should be offered to these patients

Summary

Introduction

Familial adenomatous polyposis (FAP) is a rare autosomal dominant disorder caused by mutations in the Adenomatous Polyposis Coli (APC) gene. After the initial investigation we were able to perform generation sequencing (NGS) of a cancer gene panel library (Illumina TruSight cancer Sequencing panel) This showed that the frequency of the mutation varied among different tissue types, and confirmed somatic mosaicism of the APC mutation in the patient. Her parents and siblings were tested but did not have the mutation, consistent with a de novo origin of the mutation The mutation in this patient affected codon 1450, a site of the APC gene associated with classical polyposis and desmoid development. Based on her high risk of CRC, prophylactic proctocolectomy was recommended, and she underwent laparoscopic proctocolectomy with an ileal pouch and ileoanal anastomosis without diverting ileostomy. Since the latest MRI has shown that the lesions have grown

Discussion

Conclusion

Findings

Compliance with ethical standards