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Double frameshift mutations in APC and MSH2 in the same individual
Claudio Soravia1, Celia D DeLozier, Zuzana Dobbie
1Clinic of Visceral Surgery, Geneva University Hospital, Geneva, Switzerland. csoravia@hin.ch
International Journal of Colorectal Disease
|May 6, 2006
Summary
A novel MSH2 mutation, inherited from the mother, caused Lynch syndrome (HNPCC) in a patient with familial adenomatous polyposis. The patient developed adenocarcinoma and a desmoid tumor.
Area of Science:
- Oncology
- Genetics
- Gastroenterology
Background:
- Hereditary nonpolyposis colorectal cancer (HNPCC), or Lynch syndrome, is typically linked to germline mutations in DNA mismatch repair genes.
- Familial adenomatous polyposis (FAP) is characterized by numerous adenomatous polyps and is associated with APC gene mutations.
Observation:
- A proband presented with fewer than ten polyps, atypical for FAP, prompting consideration of HNPCC.
- Microsatellite instability analysis of tumor tissue showed high-grade instability.
- Immunohistochemistry revealed absent MSH2 and MSH6 protein expression in tumor cells.
Findings:
- A prophylactic colectomy revealed a pT1N0 adenocarcinoma within a dysplastic adenoma.
- Genomic DNA analysis identified a novel frameshift mutation in MSH2 exon 7 (c.1191_1192dupG) in the proband, inherited from the mother.
- The proband also inherited an APC truncating mutation (del3471-3473GAGA) from the father.
- Follow-up revealed multiple adenomas in the stomach and duodenum, and rectal adenomas.
- The patient subsequently developed an intra-abdominal desmoid tumor.
Implications:
- This case highlights a complex genetic interplay between Lynch syndrome and FAP.
- Early diagnosis and management are crucial for patients with overlapping hereditary cancer syndromes.
- The development of desmoid tumors in this context warrants further investigation.